Neoplasms
Conditions
Keywords
leukemia, Acute myeloid leukemia, BET inhibitor, lymphoma, Myelodysplastic syndromes, Oncology, multiple myeloma, GSK525762
Brief summary
This is an open-label repeat dose, multicenter, 2-part study to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) for GSK525762 given once-daily (QD) orally. Part 1 of the study is a dose escalation phase to select the recommended Part 2 dose (RP2D) based on the safety, PK, and PD profiles observed after oral administration of GSK525762. Eligible subjects with select relapsed refractory hematological malignancies (acute myeloid leukemia \[AML\], non-Hodgkin's Lymphoma \[NHL\]and multiple myeloma \[MM\]), will be enrolled in the QD and/or BID dosing cohorts until a MTD is established. Subjects may continue treatment in the study until disease progression, unacceptable toxicity, or withdrawal of consent. . Upon determination of the MTD, twice daily (BID) dosing cohorts may be opened to collect additional safety data and evaluate the preliminary efficacy of GSK525762 administered BID. Part 2 will explore clinical activity at the MTD or RP2D; separate expansion cohorts will be planned for acute myeloid leukemia (AML), non-Hodgkin's Lymphoma (NHL, including an exploratory sub-cohort of subjects with myc and B-Cell Leukemia (BCL)2 and/or BCL6 rearrangements/overexpression \[double- and triple-hit lymphoma\]), and multiple myeloma (MM). This is the first study of this agent to be conducted in subjects with these relapsed and/or refractory hematological malignancies for which no standard therapies are anticipated to result in a durable remission.
Interventions
DRUGGSK525762
GSK525762 1 mg, 10 mg and 30 mg will be supplied as white to off-white, amorphous free base and white to slightly colored crystalline besylate tablets, round, biconvex tablets with no markings. GSK525762 will be administered with 240 milliliter (mL) water.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent provided. * Males and females 18 years old or older. * In Part 1 and, Part 2, subjects must have AML, MM, or NHL. Subjects with AML, are eligible if they • have relapsed and/or refractory disease, OR are\>=65 years of age and not candidates for or have refused standard chemotherapy. Subjects with multiple myeloma are eligible if they have progressed despite therapy with an alkylating agent, proteasome inhibitor, and immunomodulatory agent, either as individual regimens or in combination. Subjects with NHL are eligible if they have received at least two prior lines of systemic therapy, including at least one line of immunochemotherapy with an anti-CD20 antibody (if their tumor expresses CD20). In Part 2, the NHL cohort will separately enrol subjects with double- and triple hit lymphoma, so that a minimum of 10 subjects with this subset of disease will be enrolled. To be eligible for this sub-cohort, tumor sample from the subject must demonstrate rearrangement and/or overexpression of MYC and either BCL2 and/or BCL6 genes. Evaluation of double- or triple-hit status may be performed via appropriate local testing, and the determination of double- or triple-hit diagnosis will be at the discretion of the investigator and GSK Medical Monitor. * Subjects with a prior history of stem cell transplant (autologous and/or allogeneic) are allowed if * At least 3 months has elapsed from the time of transplant and * the subject has recovered from transplant-associated toxicities prior to the first dose of GSK525762, and For subjects with a prior history of allogeneic transplant, * the subject has been off systemic immunosuppressive medications (including but not limited to: cyclosporine, tacrolimus, mycophenolate mofetil, or corticosteroids) for at least 1 month prior to the first dose of GSK525762. Topical steroids are permitted * there are no signs or symptoms of graft versus host disease, other than Grade 1 skin involvement. * Eastern Cooperative Oncology Group (ECOG) performance status of \<=1. * Subject must be stable enough to be expected to complete dosing through the DLT observation period as assessed by the investigator. * Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. * A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases, a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 milli-International units per milliliter and estradiol \< 40 picograms per milliliter (\< 140 picomole per liter) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods defined in protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least two to four weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method; Child-bearing potential and agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until at least 7 months after the last dose of study medication; Negative serum pregnancy test \<= 7 days prior to first study drug dose; Female subjects who are lactating must discontinue nursing prior to the first dose of study treatment and must refrain from nursing throughout the treatment period and for 5 half-lives of GSK525762 or at least 28 days (whichever is longer) following the last dose of study treatment. * Male subjects must agree to use one of the methods of contraception specified. This method must be used from the time of the first dose of study medication until 16 weeks after the last dose of study medication. In addition, male subjects whose partners are or become pregnant must continue to use condoms for 7 days after stopping study medications. * Adequate organ system function. * Ability to comply with dietary and tobacco/alcohol abstinence requirements.
Exclusion criteria
* Haematological malignancy associated with human immunodeficiency virus (HIV) infection or solid organ transplant or history of known Hepatitis B Antigen or positive Hepatitis C antibody (confirmed by Recombinant ImmunoBlot Assay \[RIBA\], if available or alternately confirmed by Hepatitis C Virus \[HCV\] Ribonucleic acid \[RNA\]). * History or concurrent malignancy of solid tumours, except for below. Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled even if less than 5 years have elapsed since treatment. Consult the GSK Medical Monitor if unsure whether second malignancies meet requirements specified above. * Currently receiving cancer therapy (chemotherapy, radiation therapy, immuno- therapy, biologic therapy, hormonal therapy, surgery, and/or tumour embolization).The following are allowed: Hydroxyurea for proliferative disease, Corticosteroids, Use of hematopoetic growth factors is permitted at the discretion of the investigator according to published guidelines (e.g., National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), American Society of Hematology (ASH), etc.). The following are NOT allowed: Investigational anti cancer drug within 2 weeks prior to the first dose of GSK525762; Major surgery, radiotherapy, or immunotherapy within 4 weeks of GSK525762 Chemotherapy regimens with delayed toxicity within the last 4 weeks. Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks. Nitrosourea or mitomycin C within the last 6 weeks * Evidence of severe of uncontrolled infection. * Use of anticoagulants (e.g., warfarin, heparin) at therapeutic levels within 7 days prior to the first dose of GSK525762. Low dose (prophylactic) low molecular weight heparin (LMWH) is permitted. In addition, INR must be monitored in accordance with local institutional practices, as appropriate. * Current use of a prohibited medication or requires any of these medications during treatment with the investigational drugs. This includes excluding current medications known or suspected to be associated QT prolongation. In addition, any subject who is expected to require a QT prolonging medication while on trial should not be enrolled. * Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding episodes). Any serious and/or unstable pre-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator. * Symptomatic or untreated Central nervous system (CNS) disease, Subjects with a history of CNS disease (leukemia, lymphoma or myeloma) are permitted to enrol if they have previously received appropriate therapy and CNS remission has been documented. Subject with primary CNS lymphoma (defined as isolated CNS lymphoma without systemic involvement) are excluded from study. * Cardiac abnormalities as evidenced by any of the following: History or current clinically significant uncontrolled arrhythmias or hypertension; Clinically significant conduction abnormalities or arrhythmias, subjects with Bundle Branch Block; Presence of cardiac pacemaker; History or evidence of current \>=Class II congestive heart failure as defined by New York Heart Association (NYHA); History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months. * Any of the following ECG findings or assessments including: Baseline QTcF interval \>=450 milliseconds; Clinically significant ECG assessments should be reviewed by the site cardiologist prior to study entry. * GSK525762 is a benzodiazepine class molecule. Any serious known immediate or delayed hypersensitivity reaction(s) to GSK525762 or idiosyncrasy to drugs chemically related to the investigational drug. * Evidence of hemoptysis within the last 7 days. * History of major gastrointestinal bleeding within the last 3 months or any evidence of active gastrointestinal bleeding excludes the subject. * Presence of gastrointestinal disease that would significantly affect compound absorption.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Up to 86.9 weeks | Urine samples were collected to assess glucose, ketones, occult blood, urine protein, and monoclonal protein (monoclonal pro). The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase was defined as any increase in proportional concentrations relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any increase is presented. |
| Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Up to 86.9 weeks | 12-lead ECGs were recorded with the participants in a supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. |
| Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Up to 86.9 weeks | DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.0. For SBP: Grade 0 (\<=120 millimeter of mercury \[mmHg\]), Grade 1 (121-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg). For DBP: Grade 0 (\<=80 mmHg), Grade 1 (81-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg). Higher grade indicates greater severity. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. An increase is defined as an increase in grade relative to Baseline grade. Number of participants with increase to Grade 3 from Baseline is presented. |
| Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Up to 86.9 weeks | Vital signs (pulse rate and temperature) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. The clinical concern ranges were: For pulse rate (low \<60 beats per minute \[bpm\] and high \>100 bpm); For body temperature (\<=35 degrees Celsius or \>=38 degrees Celsius). Participants were counted in the worst case category that their value changed to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged, or whose value became normal, were recorded in the To Normal or No Change category. Participants were counted twice if the participant had values that changed To Low and To High, so the percentages may not add to 100%. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. |
| Part 2: Objective Response Rate Lasting at Least 4 Months (ORR4) (CTCL Cohorts) | Up to 36.4 weeks | ORR4 for CTCL cohorts is defined as the percentage of participants that have achieved a CR or PR lasting at least 4 months per global response criteria and the modified severity weighted assessment tool (mSWAT). ORR4 and 95% exact confidence interval is presented. |
| Part 2: Objective Response Rate (ORR) (MDS Cohort) | Up to 36.4 weeks | ORR for MDS cohort is defined as the percentage of participants achieving Complete Response (CR), Marrow CR, CRp (as per CR but platelet count \<100 x 10\^9 cells/Liter\[L\]), CRi (as per CR but platelet count \<100 x 10\^9cells/L or neutrophil count \<1 x 10\^9 cells/L), or Partial Response (PR) per response criteria. Complete response is defined as bone marrow \<=5% myeloblasts with normal maturation of all cell lines, with hemoglobin concentration of \>=11 grams per deciliter (g/dL), absolute neutrophil count \>=1 x 10\^9 cells/L, platelet count \>=100x10\^9 cells/L and 0% blasts in the peripheral blood. Marrow CR is defined as Bone marrow \<=5% myeloblasts and decrease by \>=50% over pre-treatment. Objective response rate was determined by the investigator according to international myeloma working group (IMWG) response criteria. |
| Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Up to 86.9 weeks | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect. AELD is adverse events leading to permanent discontinuation of study treatment. |
| Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Up to 3 weeks | An event was considered DLT if it occurred within first 3weeks of treatment & met one of following criteria:unless it was clearly established that event is unrelated to treatment:Grade4 neutropenia persisting for \>=7 days/febrile neutropenia not responding to treatment within 24hours, Grade4 thrombocytopenia lasting more than 7day & not responding to transfusions/Grade3 thrombocytopenia associated with bleeding (\>10milliliter \[mL\]), Drug-related Grade 3/4 non-hematologic toxicity as described in National Cancer Institute-Common Terminology Criteria for Adverse Events(NCI-CTCAE)version 4.0, Drug-related Grade2 non-hematological toxicity, Grade2 Troponin T elevation(central laboratory\>Upper Limit of Normal\[ULN\]),measured on two separate occasions within 48 hours, Treatment delay of 14 days/greater due to unresolved drug-related toxicity,ALT\>=3xULN+bilirubin\>=2xULN(\>35% direct)/Alanine aminotransferase(ALT) between 3-5xULN with bilirubin\<2xULN but with hepatitis symptom/rash/ALT\>=5xULN. |
| Part 1: Number of Participants With Dose Reductions | Up to 86.9 weeks | Number of participants with dose reductions due to any reason is presented. |
| Part 1: Number of Participants With Any Dose Interruptions or Delays | Up to 86.9 weeks | Number of participants with any dose interruptions/ delays is presented. |
| Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Up to 86.9 weeks | Blood samples were collected for the analysis of following clinical chemistry parameters: glucose, prothrombin international normalized ratio (Pro. INR), albumin, amylase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, calcium, calcium ionized, cholesterol, creatinine, creatine kinase, lipase, potassium, magnesium, sodium, triglycerides, alkaline phosphatase (ALP). Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Higher grade indicates greater severity. An increase was defined as an increase relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented. |
| Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Up to 86.9 weeks | Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Higher grade indicates greater severity. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Accumulation Ratio (RO) of GSK525762 | Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. Accumulation ratio was calculated by taking ratio of AUC(0-24) in Week 2 Day 7 to AUC (0-24) in Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. |
| Part 2: Apparent Clearance (CL/F) of GSK525762 After Single Dose Administration | Week 1 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. |
| Part 2: Apparent Clearance (CL/F) of GSK525762 After Repeat Dose Administration | Week 3 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. |
| Part 2: Apparent Central Volume of Distribution (V1/F) of GSK525762 Following Single Dose Administration | Week 1 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. |
| Part 2: Apparent Central Volume of Distribution (V1/F) of GSK525762 Following Repeat Dose Administration | Week 3 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. |
| Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. |
| Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. AUC(0-tau) is AUC(0-24) for repeat dose. |
| Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. |
| Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. |
| Part 1: Trough Concentration (Ctau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Week 2 Day 7: Pre-dose on Days 4, 6 and 7 | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. |
| Part 1: Tmax of GSK3529246 (Active Metabolite) Following Single Dose Administration | Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. |
| Part 1: Tmax of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. |
| Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Single Dose Administration | Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. |
| Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. |
| Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite) | Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. RS was calculated by taking ratio of AUC(0-24) on Week 2 Day 7 to AUC(0-inf) on Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. |
| Part 1: Accumulation Ratio (RO) of GSK3529246 (Active Metabolite) | Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Accumulation ratio was calculated by taking ratio of AUC(0-24) in Week 2 Day 7 to AUC (0-24) in Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. |
| Part 2: Apparent Clearance (CL/F) of GSK3529246 (Active Metabolite) Following Single Dose Administration | Week 1 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. PK parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. |
| Part 2: Apparent Clearance (CL/F) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Week 3 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. Pharmacokinetic parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. |
| Part 2: Apparent Central Volume of Distribution (V1/F) of GSK3529246 (Active Metabolite) Following Single Dose Administration | Week 1 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. Pharmacokinetic parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. |
| Part 2: Apparent Central Volume of Distribution (V1/F) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Week 3 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. Pharmacokinetic parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach. |
| Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Baseline (pre-dose Week1 Day1) and Week 3, Week 7, Week 10, Week 16 and Week 24 | The effects of treatment on disease-related symptoms/quality of life was assessed using the Skindex-29 Questionnaire, which inquires about how often (Never, Rarely, Sometimes, Often, All the time) during the previous 4 weeks the participant experienced the effect described in each of 29 items divided into 3 domains: Emotional (10 items), Symptoms (7 items) and Functioning (12 items). Responses to each item are transformed to a linear scale of 100, varying from 0 (no effect) to 100 (effect experienced all the time). Skindex-29 scores were reported as three individual domain scale scores; a scale score is the mean of a participant's responses to items in a given domain. Each domain score ranges from 0 (no effect) to 100 (effect experienced all the time), higher score implies higher impact of skin disease. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is defined is post-dose visit value minus Baseline. |
| Part 2: Number of Participants With Dose Reductions | Up to 36.4 weeks | Number of participants with dose reductions due to any reason is presented. |
| Part 2: Number of Participants With Dose Interruptions/Delays | Up to 36.4 weeks | Number of participants with any dose interruptions or delays is presented. |
| Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Up to 36.4 weeks | Blood samples were collected for the analysis of following clinical chemistry parameters: glucose, Prothrombin international normalized ratio (Pro. INR), albumin, amylase, ALT, AST, bilirubin, calcium, calcium ionized, cholesterol, creatinine, creatine kinase, lipase, potassium, magnesium, sodium, Triglycerides, ALP. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Higher grade indicates greater severity. An increase was defined as an increase relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented. |
| Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Up to 36.4 weeks | Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Higher grade indicates greater severity. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented. |
| Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Up to 36.4 weeks | Urine samples were collected to assess glucose, ketones, occult blood, urine protein. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase was defined as any increase in proportional concentrations relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any increase is presented. |
| Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Up to 36.4 weeks | Vital signs (pulse rate and temperature) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. The clinical concern ranges were: For pulse rate (low \<60 beats per minute \[bpm\] and high \>100 bpm); For body temperature (\<=35 degrees Celsius or \>=38 degrees Celsius). Participants were counted in the worst case category that their value changed to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged, or whose value became normal, were recorded in the To Normal or No Change category. Participants were counted twice if the participant had values that changed To Low and To High, so the percentages may not add to 100%. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. |
| Part 2: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: DBP and SBP | Up to 36.4 weeks | DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.0. For SBP: Grade 0 (\<=120 millimeter of mercury \[mmHg\]), Grade 1 (121-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg). For DBP: Grade 0 (\<=80 mmHg), Grade 1 (81-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg). Higher grade indicates greater severity. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. An increase is defined as an increase in grade relative to Baseline grade. Number of participants with increase to Grade 3 from Baseline is presented. |
| Part 2: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Up to 36.4 weeks | 12-lead ECGs were recorded with the participants in a supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. |
| Part 2: Progression Free Survival (PFS) | Up to 36.4 weeks | PFS defined as interval of time(in months) between date of first dose & earlier of date of disease progression & date of death due to any cause.Progression is participants(pt's)with MDS & with \<5% blasts:\>=50% increase in blasts to\>5% blasts/pt's with 5-10% blasts:\>=50% increase to \>10% blasts, for pt's with 10-20% blasts:\>=50% increase to \>20% blasts,for pt's with 20%-30% blasts:\>=50% increase to \>30% blasts, for CTCL progression is \>=25% increase in skin disease from Baseline/new tumors (T3\[1 or more tumors(\>=1cm diameter\]) in pt's with T1(Limited patches,papules&/or plaques covering \<10% of the skin surface;may further stratify into T1a \[patch only\] versus T1b \[plaque+-patch\]),T2(Patches,papules/plaques covering \>=10% of skin surface;may further stratify into T2a\[patch only\]versus T2b \[plaque+-patch\]) orT4(Confluence of erythema covering \>=80% body surface area) only skin disease/loss of response in those with CR/PR, increase of skin score of \> sum of nadir +50% Baseline score. |
| Part 2: Duration of Response (DOR) | Up to 36.4 weeks | Duration of response is defined as the time from the first documented evidence response (CR or PR lasting 4 months for CTCL; and CR, marrow CR, CRp, Cri or PR for MDS) until the first documented disease progression or death due to any cause. Median and inter-quartile range (first quartile and third quartile) of duration of response are presented. |
| Part 2: Overall Survival (OS) | Up to 36.4 weeks | OS is defined as the interval of time (in months) between the date of first dose and the date of death due to any cause. Median and inter-quartile range (first quartile and third quartile) of overall survival are presented. |
| Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs | Up to 36.4 weeks | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect. AELD is adverse events leading to permanent discontinuation of study treatment. |
| Part 1: Overall Response Rate (ORR)- Investigator Assessment | Up to 86.9 weeks | ORR is defined as the percentage of participants achieving stringent complete response (sCR), very good partial response (VGPR), partial response (PR) or minimal response (MR) for multiple myeloma (MM); CR or PR for Non-Hodgkin's Lymphoma (NHL); CR, CRp, CRi or PR for Acute Myeloid Leukemia (AML); CR, MR or PR for Myelodysplastic Syndrome (MDS) using the International Working Group (IWG) response criteria and IWG response criteria in myelodysplasia. |
| Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. |
| Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. AUC(0-24) represents AUC(0-tau) for repeat dose. |
| Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. |
| Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. |
| Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | Week 2 Day 7: Pre-dose on Days 4, 6 and 7 | Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. |
| Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. |
| Part 1: Tmax of GSK525762 Following Repeat Dose Administration | Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. |
| Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. |
| Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. |
| Part 1: Time Invariance (RS) of GSK525762 | Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose | Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. RS was calculated by taking ratio of AUC(0-24) on Week 2 Day 7 to AUC(0-inf) on Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Time to Progression (TTP) for Participants With MM | Up to 36.4 weeks | Time to Progression was planned to be analyzed. |
| Part 1: Overall Survival (OS) | Up to 86.9 weeks | Overall survival (defined as the interval of time in months between the date of first dose and the date of death due to any cause) was planned to be analyzed. |
| Part 2: Number of Participants With Dose /Exposure Markers Related Change in Molecular Markers in Tumor Tissue and/or Peripheral Blood Samples | Up to 36.4 weeks | Number of participants with dose /exposure markers related change in molecular markers (e.g. gene transcription and/or expression of proteins regulated by Bromodomain proteins) in tumor tissue and/or peripheral blood samples were planned to be analyzed. |
| Part 2: Plasma Concentrations of GSK525762 in Relationship With Safety and Efficacy Parameters Derived From Pharmacokinetic/Pharmacodynamic (PK/PD) Model | Up to 36.4 weeks | Plasma concentrations of GSK525762 in relationship with safety and efficacy parameters derived from PK/PD model was planned to be analyzed. |
| Part 1: Number of Participants With Dose /Exposure Markers Related Change in Molecular Markers in Tumor Tissue and/or Peripheral Blood Samples | Up to 86.9 weeks | Number of participants with dose /exposure markers related change in molecular markers (e.g. gene transcription and/or expression of proteins regulated by Bromodomain \[BRD\] proteins) in tumor tissue and/or peripheral blood samples were planned to be analyzed. |
| Part 1: Changes in Cardiac QT Duration Corrected for Heart Rate by Fridericia's Formula (QTcF) and Other Safety Parameters in Relation to GSK525762 PK Concentrations | Up to 86.9 weeks | Changes in QTcF and other safety parameters in relation to GSK525762 PK concentrations was planned to be analyzed. |
Countries
Australia, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
This was an open-label repeat dose, multicenter study to investigate the safety, pharmacokinetics (PK), pharmacodynamics and clinical activity of GSK525762 in participants with relapsed, refractory hematologic malignancies. The study was conducted in 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion)
Pre-assignment details
A total of 111 participants were enrolled (87 participants in Part 1 and 24 participants in Part 2) across the study centers in Australia, Spain, Great Britain, South Korea and United State of America (USA).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: GSK525762 5 mg QD Participants were administered once daily oral dose of 5 milligrams (mg) GSK525762. | 1 |
| Part 1: GSK525762 10 mg QD Participants were administered once daily oral dose of 10 mg GSK525762. | 1 |
| Part 1: GSK525762 20 mg QD Participants were administered once daily oral dose of 20 mg GSK525762. | 1 |
| Part 1: GSK525762 30 mg QD MM Participants with multiple myeloma (MM) were administered once daily oral dose of 30 mg GSK525762. | 5 |
| Part 1: GSK525762 40 mg QD Participants were administered once daily oral dose of 40 mg GSK525762. | 1 |
| Part 1: GSK525762 40 mg QD MM Participants with MM were administered once daily oral dose of 40 mg GSK525762. | 4 |
| Part 1: GSK525762 60 mg QD AML Participants with Acute Myeloid Leukemia (AML) were administered once daily oral dose of 60 mg GSK525762. | 8 |
| Part 1: GSK525762 60 mg QD NHL Participants with Non-Hodgkin's Lymphoma (NHL) were administered once daily oral dose of 60 mg GSK525762. | 18 |
| Part 1: GSK525762 60 mg QD MM Participants with MM were administered once daily oral dose of 60 mg GSK525762. | 3 |
| Part 1: GSK525762 75 mg QD AML Participants with AML were administered once daily oral dose of 75 mg GSK525762. | 8 |
| Part 1: GSK525762 80 mg QD Participants were administered once daily oral dose of 80 mg GSK525762. | 1 |
| Part 1: GSK525762 80 mg QD AML Participants with AML were administered once daily oral dose of 80 mg GSK525762. | 7 |
| Part 1: GSK525762 80 mg QD NHL Participants with NHL were administered once daily oral dose of 80 mg GSK525762. | 7 |
| Part 1: GSK525762 100 mg QD AML Participants with AML were administered once daily oral dose of 100 mg GSK525762. | 16 |
| Part 1: GSK525762 120 mg QD AML Participants with AML were administered once daily oral dose of 120 mg GSK525762. | 6 |
| Part 2: GSK525762 60 mg QD CTCL Participants Cutaneous T cell lymphoma (CTCL) were administered once daily oral dose of 60 mg GSK525762. | 7 |
| Part 2: GSK525762 75 mg QD MDS Participants with Myelodysplastic Syndrome (MDS) were administered once daily oral dose of 75 mg GSK525762. | 16 |
| Part 2: GSK525762 80 mg QD CTCL Participants CTCL were administered once daily oral dose of 80 mg GSK525762 | 1 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 (Up to 86.9 Weeks) | Investigator discretion | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part 1 (Up to 86.9 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1 (Up to 86.9 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 (Up to 36.4 Weeks) | Study closed/terminated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 3 | 1 |
| Part 2 (Up to 36.4 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1: GSK525762 10 mg QD | Part 1: GSK525762 20 mg QD | Part 1: GSK525762 30 mg QD MM | Part 1: GSK525762 40 mg QD | Part 1: GSK525762 40 mg QD MM | Part 1: GSK525762 60 mg QD AML | Part 1: GSK525762 60 mg QD NHL | Part 1: GSK525762 60 mg QD MM | Part 1: GSK525762 75 mg QD AML | Part 1: GSK525762 5 mg QD | Part 1: GSK525762 80 mg QD | Part 1: GSK525762 80 mg QD AML | Part 1: GSK525762 80 mg QD NHL | Part 1: GSK525762 100 mg QD AML | Part 1: GSK525762 120 mg QD AML | Part 2: GSK525762 60 mg QD CTCL | Part 2: GSK525762 75 mg QD MDS | Part 2: GSK525762 80 mg QD CTCL | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-64 years | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 3 Participants | 3 Participants | 11 Participants | 3 Participants | 3 Participants | 1 Participants | 0 Participants | 3 Participants | 4 Participants | 7 Participants | 4 Participants | 4 Participants | 1 Participants | 0 Participants | 51 Participants |
| Age, Customized 65-74 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 5 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 9 Participants | 1 Participants | 36 Participants |
| Age, Customized >74 years | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 6 Participants | 1 Participants | 1 Participants | 6 Participants | 0 Participants | 24 Participants |
| Race/Ethnicity, Customized Asian and native hawaiian or other pacific islander | NA Participants | NA Participants | 0 Participants | NA Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants | NA Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants | NA Participants |
| Race/Ethnicity, Customized Black or African american | NA Participants | NA Participants | 0 Participants | NA Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | NA Participants | NA Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | NA Participants | NA Participants |
| Race/Ethnicity, Customized Japanese Heritage(H)/eastAsian (H)/Southeast Asian (H) | NA Participants | NA Participants | 2 Participants | NA Participants | 0 Participants | 0 Participants | 5 Participants | 1 Participants | 0 Participants | NA Participants | NA Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | NA Participants | NA Participants |
| Race/Ethnicity, Customized Missing | NA Participants | NA Participants | 0 Participants | NA Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants | NA Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | NA Participants | NA Participants |
| Race/Ethnicity, Customized Native hawaiian or other pacific islander | NA Participants | NA Participants | 0 Participants | NA Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants | NA Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | NA Participants | NA Participants |
| Race/Ethnicity, Customized White | NA Participants | NA Participants | 3 Participants | NA Participants | 4 Participants | 6 Participants | 12 Participants | 1 Participants | 8 Participants | NA Participants | NA Participants | 5 Participants | 5 Participants | 14 Participants | 6 Participants | 5 Participants | 15 Participants | NA Participants | NA Participants |
| Sex: Female, Male Female | NA Participants | NA Participants | 2 Participants | NA Participants | 2 Participants | 1 Participants | 5 Participants | 1 Participants | 7 Participants | NA Participants | NA Participants | 4 Participants | 2 Participants | 6 Participants | 1 Participants | 5 Participants | 6 Participants | NA Participants | NA Participants |
| Sex: Female, Male Male | NA Participants | NA Participants | 3 Participants | NA Participants | 2 Participants | 7 Participants | 13 Participants | 2 Participants | 1 Participants | NA Participants | NA Participants | 3 Participants | 5 Participants | 10 Participants | 5 Participants | 2 Participants | 10 Participants | NA Participants | NA Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 0 / 1 | 1 / 1 | 4 / 5 | 0 / 1 | 3 / 4 | 7 / 8 | 12 / 18 | 2 / 3 | 8 / 8 | 1 / 1 | 7 / 7 | 6 / 7 | 15 / 16 | 6 / 6 | 1 / 7 | 13 / 16 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 1 | 5 / 5 | 1 / 1 | 4 / 4 | 8 / 8 | 18 / 18 | 3 / 3 | 8 / 8 | 1 / 1 | 7 / 7 | 7 / 7 | 16 / 16 | 6 / 6 | 7 / 7 | 16 / 16 | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 | 0 / 1 | 4 / 5 | 0 / 1 | 3 / 4 | 6 / 8 | 12 / 18 | 2 / 3 | 8 / 8 | 1 / 1 | 6 / 7 | 7 / 7 | 14 / 16 | 6 / 6 | 5 / 7 | 12 / 16 | 1 / 1 |
Outcome results
Primary
Part 1: Number of Participants With Any Dose Interruptions or Delays
Number of participants with any dose interruptions/ delays is presented.
Time frame: Up to 86.9 weeks
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Any Dose Interruptions or Delays | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Any Dose Interruptions or Delays | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Any Dose Interruptions or Delays | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Any Dose Interruptions or Delays | 3 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Any Dose Interruptions or Delays | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Any Dose Interruptions or Delays | 3 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Any Dose Interruptions or Delays | 5 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Any Dose Interruptions or Delays | 15 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Any Dose Interruptions or Delays | 2 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Any Dose Interruptions or Delays | 7 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Any Dose Interruptions or Delays | 1 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Any Dose Interruptions or Delays | 6 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Any Dose Interruptions or Delays | 7 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Any Dose Interruptions or Delays | 13 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Any Dose Interruptions or Delays | 6 Participants |
Primary
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
An event was considered DLT if it occurred within first 3weeks of treatment & met one of following criteria:unless it was clearly established that event is unrelated to treatment:Grade4 neutropenia persisting for \>=7 days/febrile neutropenia not responding to treatment within 24hours, Grade4 thrombocytopenia lasting more than 7day & not responding to transfusions/Grade3 thrombocytopenia associated with bleeding (\>10milliliter \[mL\]), Drug-related Grade 3/4 non-hematologic toxicity as described in National Cancer Institute-Common Terminology Criteria for Adverse Events(NCI-CTCAE)version 4.0, Drug-related Grade2 non-hematological toxicity, Grade2 Troponin T elevation(central laboratory\>Upper Limit of Normal\[ULN\]),measured on two separate occasions within 48 hours, Treatment delay of 14 days/greater due to unresolved drug-related toxicity,ALT\>=3xULN+bilirubin\>=2xULN(\>35% direct)/Alanine aminotransferase(ALT) between 3-5xULN with bilirubin\<2xULN but with hepatitis symptom/rash/ALT\>=5xULN.
Time frame: Up to 3 weeks
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
Primary
Part 1: Number of Participants With Dose Reductions
Number of participants with dose reductions due to any reason is presented.
Time frame: Up to 86.9 weeks
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Dose Reductions | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Dose Reductions | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Dose Reductions | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Dose Reductions | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Dose Reductions | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Dose Reductions | 1 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Dose Reductions | 0 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Dose Reductions | 8 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Dose Reductions | 0 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Dose Reductions | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Dose Reductions | 0 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Dose Reductions | 0 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Dose Reductions | 5 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Dose Reductions | 3 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Dose Reductions | 1 Participants |
Primary
Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters
Blood samples were collected for the analysis of following clinical chemistry parameters: glucose, prothrombin international normalized ratio (Pro. INR), albumin, amylase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, calcium, calcium ionized, cholesterol, creatinine, creatine kinase, lipase, potassium, magnesium, sodium, triglycerides, alkaline phosphatase (ALP). Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Higher grade indicates greater severity. An increase was defined as an increase relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented.
Time frame: Up to 86.9 weeks
Population: All Treated Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 3 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 2 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 3 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 2 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 3 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 0 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 5 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 3 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 3 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 0 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 0 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 16 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 10 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 7 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 4 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 5 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 5 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 8 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 2 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 5 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 5 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 4 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 4 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 0 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 0 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 2 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 2 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 3 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 5 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 8 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 3 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 7 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 5 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 3 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 0 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 2 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 5 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 3 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 2 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 2 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 5 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 4 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 4 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 2 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 5 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 5 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 2 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 4 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 5 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 8 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 3 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 12 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 3 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 0 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 4 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 7 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 8 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 8 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 9 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 15 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 6 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=0,1,1,5,1,3,4,16,3,4,0,6,5,11,4 | 3 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium,n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=1,1,1,4,1,4,7,17,3,8,1,7,7,15,6 | 2 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 2 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=1,1,1,5,1,4,7,18,3,8,1,7,6,16,6 | 3 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=1,1,1,5,1,4,8,18,3,8,1,7,7,15,6 | 0 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=1,1,1,5,1,4,6,18,3,8,1,7,6,15,6 | 1 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,5 | 0 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=1,1,1,2,1,4,8,18,3,7,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=1,1,1,5,1,4,8,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol,n=1,1,1,4,1,4,3,17,3,6,1,7,6,10,3 | 0 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 5 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
Primary
Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Higher grade indicates greater severity. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented.
Time frame: Up to 86.9 weeks
Population: All Treated Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 4 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 3 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 3 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 3 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 4 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 1 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 13 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 11 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 6 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 17 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 9 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 2 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 2 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 5 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 5 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 1 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 5 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 2 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 6 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 5 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 3 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 7 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 6 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 4 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 9 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 11 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 9 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 10 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 3 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 2 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,6 | 5 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes, n=1,1,1,5,1,4,7,18,3,8,1,7,7,16,6 | 3 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils, n=1,1,0,5,1,4,7,18,3,8,1,7,7,15,5 | 1 Participants |
Primary
Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.0. For SBP: Grade 0 (\<=120 millimeter of mercury \[mmHg\]), Grade 1 (121-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg). For DBP: Grade 0 (\<=80 mmHg), Grade 1 (81-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg). Higher grade indicates greater severity. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. An increase is defined as an increase in grade relative to Baseline grade. Number of participants with increase to Grade 3 from Baseline is presented.
Time frame: Up to 86.9 weeks
Population: All Treated Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 1 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 1 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 1 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 0 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 1 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 1 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 4 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 1 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 1 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 4 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 4 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | 0 Participants |
Primary
Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect. AELD is adverse events leading to permanent discontinuation of study treatment.
Time frame: Up to 86.9 weeks
Population: All Treated Population consists of all participants that received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 5 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 4 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 3 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 4 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 1 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 3 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 8 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 6 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 12 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 18 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 3 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 3 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 2 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 0 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 8 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 8 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 2 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 0 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 3 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 6 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 7 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 7 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 7 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 1 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 16 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 8 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 14 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | SAEs | 6 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | AELD | 2 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) and AE Leading to Discontinuation (AELD) | Non-serious AEs | 6 Participants |
Primary
Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading)
12-lead ECGs were recorded with the participants in a supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time frame: Up to 86.9 weeks
Population: All Treated Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 4 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 3 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 1 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 1 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 6 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 1 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 17 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 0 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 3 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 5 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 3 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 1 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 7 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 0 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 5 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 2 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 4 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 12 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 5 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 1 Participants |
Primary
Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were collected to assess glucose, ketones, occult blood, urine protein, and monoclonal protein (monoclonal pro). The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase was defined as any increase in proportional concentrations relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any increase is presented.
Time frame: Up to 86.9 weeks
Population: All Treated Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 3 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 2 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 2 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 2 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Monoclonal pro, n=0,0,0,0,0,1,0,0,2,0,0,0,0,0,0 | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 0 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 1 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 0 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 1 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 3 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 0 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 5 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 1 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 4 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Monoclonal pro, n=0,0,0,0,0,1,0,0,2,0,0,0,0,0,0 | 0 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 0 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 0 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 3 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 0 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 2 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 3 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 3 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 2 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 1 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 0 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 4 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 1 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 0 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 0 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 2 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 2 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 3 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 3 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 4 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 2 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 3 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=1,1,1,4,1,4,2,12,1,5,0,3,4,7,1 | 1 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=1,1,1,4,1,4,4,13,3,5,1,6,5,11,2 | 1 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=1,1,1,4,1,4,4,15, 3,5,0,3,5,8,1 | 1 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=1,1,1,4,1,4,5,14,3,7,1,6,5,11,2 | 1 Participants |
Primary
Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature
Vital signs (pulse rate and temperature) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. The clinical concern ranges were: For pulse rate (low \<60 beats per minute \[bpm\] and high \>100 bpm); For body temperature (\<=35 degrees Celsius or \>=38 degrees Celsius). Participants were counted in the worst case category that their value changed to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged, or whose value became normal, were recorded in the To Normal or No Change category. Participants were counted twice if the participant had values that changed To Low and To High, so the percentages may not add to 100%. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date.
Time frame: Up to 86.9 weeks
Population: All Treated Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 4 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 3 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 1 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 2 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 1 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 40 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 2 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 2 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 1 Participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 2 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 2 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 4 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 3 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 2 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 4 Participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 10 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 3 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 15 Participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 8 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 2 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 3 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 0 Participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 1 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 5 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 7 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 1 Participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 3 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 1 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 80 mg QD | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 1 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 1 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 1 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 6 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 6 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 1 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 1 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 6 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 0 Participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 6 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 8 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 8 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 1 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 1 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 8 Participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 7 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 6 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 4 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High, | 0 Participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 2 Participants |
Primary
Part 2: Objective Response Rate Lasting at Least 4 Months (ORR4) (CTCL Cohorts)
ORR4 for CTCL cohorts is defined as the percentage of participants that have achieved a CR or PR lasting at least 4 months per global response criteria and the modified severity weighted assessment tool (mSWAT). ORR4 and 95% exact confidence interval is presented.
Time frame: Up to 36.4 weeks
Population: All Treated Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Objective Response Rate Lasting at Least 4 Months (ORR4) (CTCL Cohorts) | 0 Percentage of participants |
| Part 1: GSK525762 10 mg QD | Part 2: Objective Response Rate Lasting at Least 4 Months (ORR4) (CTCL Cohorts) | 0 Percentage of participants |
Primary
Part 2: Objective Response Rate (ORR) (MDS Cohort)
ORR for MDS cohort is defined as the percentage of participants achieving Complete Response (CR), Marrow CR, CRp (as per CR but platelet count \<100 x 10\^9 cells/Liter\[L\]), CRi (as per CR but platelet count \<100 x 10\^9cells/L or neutrophil count \<1 x 10\^9 cells/L), or Partial Response (PR) per response criteria. Complete response is defined as bone marrow \<=5% myeloblasts with normal maturation of all cell lines, with hemoglobin concentration of \>=11 grams per deciliter (g/dL), absolute neutrophil count \>=1 x 10\^9 cells/L, platelet count \>=100x10\^9 cells/L and 0% blasts in the peripheral blood. Marrow CR is defined as Bone marrow \<=5% myeloblasts and decrease by \>=50% over pre-treatment. Objective response rate was determined by the investigator according to international myeloma working group (IMWG) response criteria.
Time frame: Up to 36.4 weeks
Population: All Treated Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Objective Response Rate (ORR) (MDS Cohort) | 25 Percentage of participants |
Secondary
Part 1: Accumulation Ratio (RO) of GSK3529246 (Active Metabolite)
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Accumulation ratio was calculated by taking ratio of AUC(0-24) in Week 2 Day 7 to AUC (0-24) in Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.
Time frame: Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 30 mg QD MM | Part 1: Accumulation Ratio (RO) of GSK3529246 (Active Metabolite) | 1.18 Ratio | Geometric Coefficient of Variation 25.71 |
| Part 1: GSK525762 40 mg QD MM | Part 1: Accumulation Ratio (RO) of GSK3529246 (Active Metabolite) | 1.02 Ratio | — |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Accumulation Ratio (RO) of GSK3529246 (Active Metabolite) | 1.61 Ratio | Geometric Coefficient of Variation 31.61 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Accumulation Ratio (RO) of GSK3529246 (Active Metabolite) | 0.90 Ratio | — |
| Part 1: GSK525762 75 mg QD AML | Part 1: Accumulation Ratio (RO) of GSK3529246 (Active Metabolite) | 1.56 Ratio | Geometric Coefficient of Variation 26.04 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Accumulation Ratio (RO) of GSK3529246 (Active Metabolite) | 1.20 Ratio | Geometric Coefficient of Variation 11.5 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Accumulation Ratio (RO) of GSK3529246 (Active Metabolite) | 3.22 Ratio | Geometric Coefficient of Variation 59.05 |
Secondary
Part 1: Accumulation Ratio (RO) of GSK525762
Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. Accumulation ratio was calculated by taking ratio of AUC(0-24) in Week 2 Day 7 to AUC (0-24) in Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Accumulation Ratio (RO) of GSK525762 | 1.04 Ratio | — |
| Part 1: GSK525762 10 mg QD | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.64 Ratio | — |
| Part 1: GSK525762 20 mg QD | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.64 Ratio | — |
| Part 1: GSK525762 30 mg QD MM | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.74 Ratio | Geometric Coefficient of Variation 36.67 |
| Part 1: GSK525762 40 mg QD | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.75 Ratio | — |
| Part 1: GSK525762 40 mg QD MM | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.68 Ratio | Geometric Coefficient of Variation 17.66 |
| Part 1: GSK525762 60 mg QD AML | Part 1: Accumulation Ratio (RO) of GSK525762 | 1.06 Ratio | Geometric Coefficient of Variation 13.47 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.67 Ratio | Geometric Coefficient of Variation 29.24 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.33 Ratio | Geometric Coefficient of Variation 47.64 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.81 Ratio | Geometric Coefficient of Variation 45.7 |
| Part 1: GSK525762 80 mg QD | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.87 Ratio | — |
| Part 1: GSK525762 80 mg QD AML | Part 1: Accumulation Ratio (RO) of GSK525762 | 1.01 Ratio | Geometric Coefficient of Variation 33.69 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.75 Ratio | Geometric Coefficient of Variation 20.27 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.81 Ratio | Geometric Coefficient of Variation 82.45 |
| Part 1: GSK525762 120 mg QD AML | Part 1: Accumulation Ratio (RO) of GSK525762 | 0.71 Ratio | Geometric Coefficient of Variation 24.96 |
Secondary
Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population consisted of all participants in the All Treated Population for whom a PK sample was obtained and analyzed. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 460.48 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 5 mg QD | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 466.81 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 10 mg QD | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 1092.28 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 10 mg QD | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 1024.49 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 20 mg QD | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 3054.11 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 20 mg QD | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 2881.41 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 30 mg QD MM | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 2146.54 Hours*nanograms per milliliter | Geometric Coefficient of Variation 31.68 |
| Part 1: GSK525762 30 mg QD MM | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 2217.32 Hours*nanograms per milliliter | Geometric Coefficient of Variation 32.55 |
| Part 1: GSK525762 40 mg QD | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 3465.49 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 40 mg QD | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 3317.10 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 40 mg QD MM | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 2510.55 Hours*nanograms per milliliter | Geometric Coefficient of Variation 71.29 |
| Part 1: GSK525762 40 mg QD MM | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 2546.49 Hours*nanograms per milliliter | Geometric Coefficient of Variation 72.05 |
| Part 1: GSK525762 60 mg QD AML | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 6424.74 Hours*nanograms per milliliter | Geometric Coefficient of Variation 22.42 |
| Part 1: GSK525762 60 mg QD AML | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 6951.06 Hours*nanograms per milliliter | Geometric Coefficient of Variation 25.12 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 6214.97 Hours*nanograms per milliliter | Geometric Coefficient of Variation 60.67 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 5918.90 Hours*nanograms per milliliter | Geometric Coefficient of Variation 52.85 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 3695.32 Hours*nanograms per milliliter | Geometric Coefficient of Variation 62.01 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 3874.05 Hours*nanograms per milliliter | Geometric Coefficient of Variation 63.27 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 7980.72 Hours*nanograms per milliliter | Geometric Coefficient of Variation 45.28 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 8248.45 Hours*nanograms per milliliter | Geometric Coefficient of Variation 47.87 |
| Part 1: GSK525762 80 mg QD | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 6032.36 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 80 mg QD | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 5944.52 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 80 mg QD AML | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 8394.69 Hours*nanograms per milliliter | Geometric Coefficient of Variation 34.31 |
| Part 1: GSK525762 80 mg QD AML | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 9734.83 Hours*nanograms per milliliter | Geometric Coefficient of Variation 29.6 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 5114.61 Hours*nanograms per milliliter | Geometric Coefficient of Variation 44.76 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 5017.96 Hours*nanograms per milliliter | Geometric Coefficient of Variation 44.17 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 13520.57 Hours*nanograms per milliliter | Geometric Coefficient of Variation 46.29 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 14635.17 Hours*nanograms per milliliter | Geometric Coefficient of Variation 52.35 |
| Part 1: GSK525762 120 mg QD AML | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-24), n=1,1,1,5,1,4,8,18,3,8,1,6,7,16, 6 | 13688.54 Hours*nanograms per milliliter | Geometric Coefficient of Variation 43.8 |
| Part 1: GSK525762 120 mg QD AML | Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours(AUC[0-24]) and AUC Extrapolated to Infinity (AUC[0-inf]) of GSK525762 Following Single Dose Administration | AUC(0-inf), n=1,1,1,5,1,4,7,17,3,8,1,5,7,16,5 | 17021.44 Hours*nanograms per milliliter | Geometric Coefficient of Variation 35.37 |
Secondary
Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration
Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. AUC(0-24) represents AUC(0-tau) for repeat dose.
Time frame: Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 476.71 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 5 mg QD | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 476.71 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 10 mg QD | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 656.93 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 10 mg QD | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 656.93 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 20 mg QD | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 1855.07 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 20 mg QD | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 1855.07 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 30 mg QD MM | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 1908.18 Hours*nanograms per milliliter | Geometric Coefficient of Variation 27.53 |
| Part 1: GSK525762 30 mg QD MM | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 1908.18 Hours*nanograms per milliliter | Geometric Coefficient of Variation 27.53 |
| Part 1: GSK525762 40 mg QD | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 2490.25 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 40 mg QD | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 2490.25 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 40 mg QD MM | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 1702.37 Hours*nanograms per milliliter | Geometric Coefficient of Variation 58.17 |
| Part 1: GSK525762 40 mg QD MM | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 1702.37 Hours*nanograms per milliliter | Geometric Coefficient of Variation 58.17 |
| Part 1: GSK525762 60 mg QD AML | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 6271.43 Hours*nanograms per milliliter | Geometric Coefficient of Variation 38.76 |
| Part 1: GSK525762 60 mg QD AML | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 6271.43 Hours*nanograms per milliliter | Geometric Coefficient of Variation 38.76 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 3576.49 Hours*nanograms per milliliter | Geometric Coefficient of Variation 30.59 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 3576.49 Hours*nanograms per milliliter | Geometric Coefficient of Variation 30.59 |
| Part 1: GSK525762 60 mg QD MM | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 931.02 Hours*nanograms per milliliter | Geometric Coefficient of Variation 53.64 |
| Part 1: GSK525762 60 mg QD MM | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 931.02 Hours*nanograms per milliliter | Geometric Coefficient of Variation 53.64 |
| Part 1: GSK525762 75 mg QD AML | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 5883.76 Hours*nanograms per milliliter | Geometric Coefficient of Variation 48.48 |
| Part 1: GSK525762 75 mg QD AML | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 5883.76 Hours*nanograms per milliliter | Geometric Coefficient of Variation 48.48 |
| Part 1: GSK525762 80 mg QD | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 5188.25 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 80 mg QD | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 5188.25 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 80 mg QD AML | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 6892.57 Hours*nanograms per milliliter | Geometric Coefficient of Variation 71.96 |
| Part 1: GSK525762 80 mg QD AML | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 6892.57 Hours*nanograms per milliliter | Geometric Coefficient of Variation 71.96 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 2994.24 Hours*nanograms per milliliter | Geometric Coefficient of Variation 37.27 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 2994.24 Hours*nanograms per milliliter | Geometric Coefficient of Variation 37.27 |
| Part 1: GSK525762 100 mg QD AML | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 9440.98 Hours*nanograms per milliliter | Geometric Coefficient of Variation 84.11 |
| Part 1: GSK525762 100 mg QD AML | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 9440.98 Hours*nanograms per milliliter | Geometric Coefficient of Variation 84.11 |
| Part 1: GSK525762 120 mg QD AML | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-24) | 5296.46 Hours*nanograms per milliliter | Geometric Coefficient of Variation 8.89 |
| Part 1: GSK525762 120 mg QD AML | Part 1: AUC(0-24) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK525762 Following Repeat Dose Administration | AUC(0-tau) | 5296.46 Hours*nanograms per milliliter | Geometric Coefficient of Variation 8.89 |
Secondary
Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration
Plasma samples for PK analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.
Time frame: Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK525762 30 mg QD MM | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-inf), n=0,0,0,5,0,1,0,10, 2,7,0,0,6,7,0 | 1691.75 Hours*nanograms per milliliter | Geometric Coefficient of Variation 28.96 |
| Part 1: GSK525762 30 mg QD MM | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-24), n=0,0,0,5,0,1,0,15, 2,8,0,0,6,15,0 | 1368.11 Hours*nanograms per milliliter | Geometric Coefficient of Variation 31.39 |
| Part 1: GSK525762 40 mg QD MM | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-24), n=0,0,0,5,0,1,0,15, 2,8,0,0,6,15,0 | 1891.48 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 40 mg QD MM | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-inf), n=0,0,0,5,0,1,0,10, 2,7,0,0,6,7,0 | 2013.33 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 60 mg QD NHL | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-24), n=0,0,0,5,0,1,0,15, 2,8,0,0,6,15,0 | 3048.33 Hours*nanograms per milliliter | Geometric Coefficient of Variation 22.85 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-inf), n=0,0,0,5,0,1,0,10, 2,7,0,0,6,7,0 | 3684.96 Hours*nanograms per milliliter | Geometric Coefficient of Variation 28.5 |
| Part 1: GSK525762 60 mg QD MM | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-24), n=0,0,0,5,0,1,0,15, 2,8,0,0,6,15,0 | 3297.95 Hours*nanograms per milliliter | Geometric Coefficient of Variation 68.31 |
| Part 1: GSK525762 60 mg QD MM | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-inf), n=0,0,0,5,0,1,0,10, 2,7,0,0,6,7,0 | 4499.65 Hours*nanograms per milliliter | Geometric Coefficient of Variation 72.79 |
| Part 1: GSK525762 75 mg QD AML | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-inf), n=0,0,0,5,0,1,0,10, 2,7,0,0,6,7,0 | 4003.48 Hours*nanograms per milliliter | Geometric Coefficient of Variation 42.09 |
| Part 1: GSK525762 75 mg QD AML | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-24), n=0,0,0,5,0,1,0,15, 2,8,0,0,6,15,0 | 3174.42 Hours*nanograms per milliliter | Geometric Coefficient of Variation 40.63 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-24), n=0,0,0,5,0,1,0,15, 2,8,0,0,6,15,0 | 3432.89 Hours*nanograms per milliliter | Geometric Coefficient of Variation 39.76 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-inf), n=0,0,0,5,0,1,0,10, 2,7,0,0,6,7,0 | 3908.15 Hours*nanograms per milliliter | Geometric Coefficient of Variation 41.2 |
| Part 1: GSK525762 100 mg QD AML | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-24), n=0,0,0,5,0,1,0,15, 2,8,0,0,6,15,0 | 2901.79 Hours*nanograms per milliliter | Geometric Coefficient of Variation 52.33 |
| Part 1: GSK525762 100 mg QD AML | Part 1: AUC(0-24) and AUC[0-inf] of GSK3529246 (Active Metabolite) Following Single Dose Administration | AUC(0-inf), n=0,0,0,5,0,1,0,10, 2,7,0,0,6,7,0 | 4714.85 Hours*nanograms per milliliter | Geometric Coefficient of Variation 48.39 |
Secondary
Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762. AUC(0-tau) is AUC(0-24) for repeat dose.
Time frame: Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK525762 30 mg QD MM | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-24) | 1517.96 Hours*nanograms per milliliter | Geometric Coefficient of Variation 33.88 |
| Part 1: GSK525762 30 mg QD MM | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-tau) | 1517.96 Hours*nanograms per milliliter | Geometric Coefficient of Variation 33.88 |
| Part 1: GSK525762 40 mg QD MM | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-24) | 1922.77 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 40 mg QD MM | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-tau) | 1922.77 Hours*nanograms per milliliter | — |
| Part 1: GSK525762 60 mg QD NHL | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-24) | 4870.28 Hours*nanograms per milliliter | Geometric Coefficient of Variation 46.15 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-tau) | 4870.28 Hours*nanograms per milliliter | Geometric Coefficient of Variation 46.15 |
| Part 1: GSK525762 60 mg QD MM | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-tau) | 3838.35 Hours*nanograms per milliliter | Geometric Coefficient of Variation 37.18 |
| Part 1: GSK525762 60 mg QD MM | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-24) | 3838.35 Hours*nanograms per milliliter | Geometric Coefficient of Variation 37.18 |
| Part 1: GSK525762 75 mg QD AML | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-24) | 5312.66 Hours*nanograms per milliliter | Geometric Coefficient of Variation 45.3 |
| Part 1: GSK525762 75 mg QD AML | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-tau) | 5312.66 Hours*nanograms per milliliter | Geometric Coefficient of Variation 45.3 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-24) | 3379.85 Hours*nanograms per milliliter | Geometric Coefficient of Variation 44.24 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-tau) | 3379.85 Hours*nanograms per milliliter | Geometric Coefficient of Variation 44.24 |
| Part 1: GSK525762 100 mg QD AML | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-tau) | 8534.92 Hours*nanograms per milliliter | Geometric Coefficient of Variation 43.93 |
| Part 1: GSK525762 100 mg QD AML | Part 1: AUC(0-24) and AUC(0-tau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | AUC(0-24) | 8534.92 Hours*nanograms per milliliter | Geometric Coefficient of Variation 43.93 |
Secondary
Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.
Time frame: Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK525762 30 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmax | 121.83 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 26.75 |
| Part 1: GSK525762 30 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmin | 27.14 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28.38 |
| Part 1: GSK525762 40 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmax | 282.72 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 40 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmin | 15.18 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmax | 453.89 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34.07 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmin | 66.49 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 81.56 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmax | 500.61 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22.83 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmin | 40.88 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.39 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmax | 445.47 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52.02 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmin | 73.60 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 88.34 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmax | 370.67 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.23 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmin | 38.71 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56.34 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmax | 557.92 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.81 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | Cmin | 116.62 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74.25 |
Secondary
Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.
Time frame: Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK525762 30 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmax, n=0,0,0,5,0,1, 0,15,3,8,0,0,7,16,0 | 109.45 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.38 |
| Part 1: GSK525762 30 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmin, n=0,0,0,2,0,1, 0,14,3,7,0,0,6,13,0 | 2.47 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 4.29 |
| Part 1: GSK525762 40 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmax, n=0,0,0,5,0,1, 0,15,3,8,0,0,7,16,0 | 246.12 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 40 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmin, n=0,0,0,2,0,1, 0,14,3,7,0,0,6,13,0 | 66.39 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmax, n=0,0,0,5,0,1, 0,15,3,8,0,0,7,16,0 | 239.98 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 26.75 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmin, n=0,0,0,2,0,1, 0,14,3,7,0,0,6,13,0 | 18.17 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 116.63 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmin, n=0,0,0,2,0,1, 0,14,3,7,0,0,6,13,0 | 10.83 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 161.52 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmax, n=0,0,0,5,0,1, 0,15,3,8,0,0,7,16,0 | 361.30 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 54.77 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmax, n=0,0,0,5,0,1, 0,15,3,8,0,0,7,16,0 | 251.73 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49.71 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmin, n=0,0,0,2,0,1, 0,14,3,7,0,0,6,13,0 | 18.45 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 71.98 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmax, n=0,0,0,5,0,1, 0,15,3,8,0,0,7,16,0 | 325.42 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47.17 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmin, n=0,0,0,2,0,1, 0,14,3,7,0,0,6,13,0 | 12.66 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 108.08 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmin, n=0,0,0,2,0,1, 0,14,3,7,0,0,6,13,0 | 14.17 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 99.02 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Cmax and Cmin of GSK3529246 (Active Metabolite) Following Single Dose Administration | Cmax, n=0,0,0,5,0,1, 0,15,3,8,0,0,7,16,0 | 201.02 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56.94 |
Secondary
Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration
Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 102.86 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 5 mg QD | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 1.47 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 10 mg QD | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 118.59 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 10 mg QD | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 5.03 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 20 mg QD | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 550.01 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 20 mg QD | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 3.92 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 30 mg QD MM | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 387.66 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52.41 |
| Part 1: GSK525762 30 mg QD MM | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 7.72 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 103.48 |
| Part 1: GSK525762 40 mg QD | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 8.66 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 40 mg QD | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 557.60 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 40 mg QD MM | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 2.36 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 84.21 |
| Part 1: GSK525762 40 mg QD MM | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 566.59 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57.75 |
| Part 1: GSK525762 60 mg QD AML | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 1070.32 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 37.26 |
| Part 1: GSK525762 60 mg QD AML | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 57.75 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 82.69 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 1179.42 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28.1 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 7.03 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51.1 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 512.78 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48.37 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 1.63 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 141.42 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 14.00 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 112.58 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 1384.46 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.35 |
| Part 1: GSK525762 80 mg QD | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 1752.86 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 80 mg QD | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 21.02 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 80 mg QD AML | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 50.89 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 123.69 |
| Part 1: GSK525762 80 mg QD AML | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 1314.21 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 58.58 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 4.64 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 73.29 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 725.29 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 46.79 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 1587.25 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50.83 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 55.63 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 163.06 |
| Part 1: GSK525762 120 mg QD AML | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmin | 14.96 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 64.95 |
| Part 1: GSK525762 120 mg QD AML | Part 1: Cmax and Cmin of GSK525762 Following Repeat Dose Administration | Cmax | 921.35 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52.16 |
Secondary
Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration
Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 1.11 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 5 mg QD | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 90.56 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 10 mg QD | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 116.69 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 10 mg QD | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 27.86 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 20 mg QD | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 20.62 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 20 mg QD | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 559.14 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 30 mg QD MM | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 442.77 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.83 |
| Part 1: GSK525762 30 mg QD MM | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 7.55 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 73.07 |
| Part 1: GSK525762 40 mg QD | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 513.03 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 40 mg QD | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 21.20 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 40 mg QD MM | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 13.25 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 71.79 |
| Part 1: GSK525762 40 mg QD MM | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 660.79 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 71.94 |
| Part 1: GSK525762 60 mg QD AML | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 107.30 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 68.4 |
| Part 1: GSK525762 60 mg QD AML | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 853.03 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.1 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 1158.66 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28.58 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 50.49 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 139.83 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 813.87 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.91 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 29.39 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47.67 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 37.92 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 80.33 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 1728.80 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.37 |
| Part 1: GSK525762 80 mg QD | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 1248.10 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 80 mg QD | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 129.76 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 80 mg QD AML | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 71.43 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 112.42 |
| Part 1: GSK525762 80 mg QD AML | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 1444.42 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 29.92 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 1073.51 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 38.46 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 27.89 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 115.67 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 2335.99 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23.05 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 89.96 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 112.8 |
| Part 1: GSK525762 120 mg QD AML | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmin | 138.75 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 111.14 |
| Part 1: GSK525762 120 mg QD AML | Part 1: Maximum Observed Concentration (Cmax) and Minimum Plasma Concentration (Cmin) of GSK525762 Following Single Dose Administration | Cmax | 1793.39 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 42.16 |
Secondary
Part 1: Overall Response Rate (ORR)- Investigator Assessment
ORR is defined as the percentage of participants achieving stringent complete response (sCR), very good partial response (VGPR), partial response (PR) or minimal response (MR) for multiple myeloma (MM); CR or PR for Non-Hodgkin's Lymphoma (NHL); CR, CRp, CRi or PR for Acute Myeloid Leukemia (AML); CR, MR or PR for Myelodysplastic Syndrome (MDS) using the International Working Group (IWG) response criteria and IWG response criteria in myelodysplasia.
Time frame: Up to 86.9 weeks
Population: All Treated Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 0 Percentage of participants |
| Part 1: GSK525762 10 mg QD | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 0 Percentage of participants |
| Part 1: GSK525762 20 mg QD | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 0 Percentage of participants |
| Part 1: GSK525762 30 mg QD MM | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 0 Percentage of participants |
| Part 1: GSK525762 40 mg QD | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 0 Percentage of participants |
| Part 1: GSK525762 40 mg QD MM | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 0 Percentage of participants |
| Part 1: GSK525762 60 mg QD AML | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 25 Percentage of participants |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 6 Percentage of participants |
| Part 1: GSK525762 60 mg QD MM | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 0 Percentage of participants |
| Part 1: GSK525762 75 mg QD AML | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 0 Percentage of participants |
| Part 1: GSK525762 80 mg QD | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 0 Percentage of participants |
| Part 1: GSK525762 80 mg QD AML | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 14 Percentage of participants |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 29 Percentage of participants |
| Part 1: GSK525762 100 mg QD AML | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 13 Percentage of participants |
| Part 1: GSK525762 120 mg QD AML | Part 1: Overall Response Rate (ORR)- Investigator Assessment | 17 Percentage of participants |
Secondary
Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Repeat Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.
Time frame: Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GSK525762 30 mg QD MM | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 8.24 Hour |
| Part 1: GSK525762 40 mg QD MM | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 6.19 Hour |
| Part 1: GSK525762 60 mg QD NHL | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 7.97 Hour |
| Part 1: GSK525762 60 mg QD MM | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 7.39 Hour |
| Part 1: GSK525762 75 mg QD AML | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 8.00 Hour |
| Part 1: GSK525762 80 mg QD NHL | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 6.72 Hour |
| Part 1: GSK525762 100 mg QD AML | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 11.77 Hour |
Secondary
Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Single Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.
Time frame: Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GSK525762 30 mg QD MM | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Single Dose Administration | 9.90 Hour |
| Part 1: GSK525762 40 mg QD MM | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Single Dose Administration | 5.83 Hour |
| Part 1: GSK525762 60 mg QD NHL | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Single Dose Administration | 8.66 Hour |
| Part 1: GSK525762 60 mg QD MM | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Single Dose Administration | 12.72 Hour |
| Part 1: GSK525762 75 mg QD AML | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Single Dose Administration | 8.31 Hour |
| Part 1: GSK525762 80 mg QD NHL | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Single Dose Administration | 7.16 Hour |
| Part 1: GSK525762 100 mg QD AML | Part 1: T1/2 of GSK3529246 (Active Metabolite) Following Single Dose Administration | 9.23 Hour |
Secondary
Part 1: T1/2 of GSK525762 Following Repeat Dose Administration
Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 3.68 Hour |
| Part 1: GSK525762 10 mg QD | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 5.64 Hour |
| Part 1: GSK525762 20 mg QD | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 4.70 Hour |
| Part 1: GSK525762 30 mg QD MM | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 4.15 Hour |
| Part 1: GSK525762 40 mg QD | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 4.39 Hour |
| Part 1: GSK525762 40 mg QD MM | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 4.39 Hour |
| Part 1: GSK525762 60 mg QD AML | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 6.48 Hour |
| Part 1: GSK525762 60 mg QD NHL | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 3.51 Hour |
| Part 1: GSK525762 60 mg QD MM | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 1.96 Hour |
| Part 1: GSK525762 75 mg QD AML | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 3.97 Hour |
| Part 1: GSK525762 80 mg QD | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 2.54 Hour |
| Part 1: GSK525762 80 mg QD AML | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 4.98 Hour |
| Part 1: GSK525762 80 mg QD NHL | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 3.22 Hour |
| Part 1: GSK525762 100 mg QD AML | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 5.51 Hour |
| Part 1: GSK525762 120 mg QD AML | Part 1: T1/2 of GSK525762 Following Repeat Dose Administration | 4.09 Hour |
Secondary
Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration
Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 4.01 Hour |
| Part 1: GSK525762 10 mg QD | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 5.75 Hour |
| Part 1: GSK525762 20 mg QD | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 6.27 Hour |
| Part 1: GSK525762 30 mg QD MM | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 4.55 Hour |
| Part 1: GSK525762 40 mg QD | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 5.10 Hour |
| Part 1: GSK525762 40 mg QD MM | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 4.07 Hour |
| Part 1: GSK525762 60 mg QD AML | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 6.48 Hour |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 3.96 Hour |
| Part 1: GSK525762 60 mg QD MM | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 5.55 Hour |
| Part 1: GSK525762 75 mg QD AML | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 4.57 Hour |
| Part 1: GSK525762 80 mg QD | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 4.15 Hour |
| Part 1: GSK525762 80 mg QD AML | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 4.75 Hour |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 4.06 Hour |
| Part 1: GSK525762 100 mg QD AML | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 5.66 Hour |
| Part 1: GSK525762 120 mg QD AML | Part 1: Terminal Half Life (T1/2) of GSK525762 Following Single Dose Administration | 6.53 Hour |
Secondary
Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite)
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. RS was calculated by taking ratio of AUC(0-24) on Week 2 Day 7 to AUC(0-inf) on Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.
Time frame: Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 30 mg QD MM | Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite) | 0.92 Ratio | Geometric Coefficient of Variation 25.58 |
| Part 1: GSK525762 40 mg QD MM | Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite) | 0.96 Ratio | — |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite) | 1.18 Ratio | Geometric Coefficient of Variation 32.33 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite) | 0.63 Ratio | — |
| Part 1: GSK525762 75 mg QD AML | Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite) | 1.20 Ratio | Geometric Coefficient of Variation 13.74 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite) | 1.06 Ratio | Geometric Coefficient of Variation 9.48 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Time Invariance (RS) of GSK3529246 (Active Metabolite) | 1.87 Ratio | Geometric Coefficient of Variation 57.15 |
Secondary
Part 1: Time Invariance (RS) of GSK525762
Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. RS was calculated by taking ratio of AUC(0-24) on Week 2 Day 7 to AUC(0-inf) on Week 1 Day 1. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Week 1 Day 1: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose; Week 2 Day 7: pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Time Invariance (RS) of GSK525762 | 1.02 Ratio | — |
| Part 1: GSK525762 10 mg QD | Part 1: Time Invariance (RS) of GSK525762 | 0.60 Ratio | — |
| Part 1: GSK525762 20 mg QD | Part 1: Time Invariance (RS) of GSK525762 | 0.61 Ratio | — |
| Part 1: GSK525762 30 mg QD MM | Part 1: Time Invariance (RS) of GSK525762 | 0.71 Ratio | Geometric Coefficient of Variation 35.82 |
| Part 1: GSK525762 40 mg QD | Part 1: Time Invariance (RS) of GSK525762 | 0.72 Ratio | — |
| Part 1: GSK525762 40 mg QD MM | Part 1: Time Invariance (RS) of GSK525762 | 0.67 Ratio | Geometric Coefficient of Variation 18.6 |
| Part 1: GSK525762 60 mg QD AML | Part 1: Time Invariance (RS) of GSK525762 | 0.98 Ratio | Geometric Coefficient of Variation 11.73 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Time Invariance (RS) of GSK525762 | 0.65 Ratio | Geometric Coefficient of Variation 31.37 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Time Invariance (RS) of GSK525762 | 0.32 Ratio | Geometric Coefficient of Variation 53.56 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Time Invariance (RS) of GSK525762 | 0.78 Ratio | Geometric Coefficient of Variation 46.56 |
| Part 1: GSK525762 80 mg QD | Part 1: Time Invariance (RS) of GSK525762 | 0.86 Ratio | — |
| Part 1: GSK525762 80 mg QD AML | Part 1: Time Invariance (RS) of GSK525762 | 0.91 Ratio | Geometric Coefficient of Variation 36.22 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Time Invariance (RS) of GSK525762 | 0.74 Ratio | Geometric Coefficient of Variation 19.36 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Time Invariance (RS) of GSK525762 | 0.76 Ratio | Geometric Coefficient of Variation 84.74 |
| Part 1: GSK525762 120 mg QD AML | Part 1: Time Invariance (RS) of GSK525762 | 0.54 Ratio | — |
Secondary
Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration
Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 0.62 Hour |
| Part 1: GSK525762 10 mg QD | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 2.00 Hour |
| Part 1: GSK525762 20 mg QD | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 1.00 Hour |
| Part 1: GSK525762 30 mg QD MM | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 1.00 Hour |
| Part 1: GSK525762 40 mg QD | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 1.00 Hour |
| Part 1: GSK525762 40 mg QD MM | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 0.78 Hour |
| Part 1: GSK525762 60 mg QD AML | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 1.56 Hour |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 1.00 Hour |
| Part 1: GSK525762 60 mg QD MM | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 1.00 Hour |
| Part 1: GSK525762 75 mg QD AML | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 0.86 Hour |
| Part 1: GSK525762 80 mg QD | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 1.28 Hour |
| Part 1: GSK525762 80 mg QD AML | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 1.03 Hour |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 1.00 Hour |
| Part 1: GSK525762 100 mg QD AML | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 0.92 Hour |
| Part 1: GSK525762 120 mg QD AML | Part 1: Time of Maximum Concentration (Tmax) of GSK525762 Following Single Dose Administration | 1.58 Hour |
Secondary
Part 1: Tmax of GSK3529246 (Active Metabolite) Following Repeat Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.
Time frame: Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GSK525762 30 mg QD MM | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 2.48 Hour |
| Part 1: GSK525762 40 mg QD MM | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 0.60 Hour |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 1.03 Hour |
| Part 1: GSK525762 60 mg QD MM | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 1.00 Hour |
| Part 1: GSK525762 75 mg QD AML | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 2.05 Hour |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 2.02 Hour |
| Part 1: GSK525762 100 mg QD AML | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 4.00 Hour |
Secondary
Part 1: Tmax of GSK3529246 (Active Metabolite) Following Single Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. Pharmacokinetic parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.
Time frame: Week 1 Day 1: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GSK525762 30 mg QD MM | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Single Dose Administration | 1.92 Hour |
| Part 1: GSK525762 40 mg QD MM | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Single Dose Administration | 0.58 Hour |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Single Dose Administration | 2.10 Hour |
| Part 1: GSK525762 60 mg QD MM | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Single Dose Administration | 4.00 Hour |
| Part 1: GSK525762 75 mg QD AML | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Single Dose Administration | 3.15 Hour |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Single Dose Administration | 2.08 Hour |
| Part 1: GSK525762 100 mg QD AML | Part 1: Tmax of GSK3529246 (Active Metabolite) Following Single Dose Administration | 4.03 Hour |
Secondary
Part 1: Tmax of GSK525762 Following Repeat Dose Administration
Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Week 2 Day 7: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post-dose
Population: PK Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 0.67 Hour |
| Part 1: GSK525762 10 mg QD | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 0.00 Hour |
| Part 1: GSK525762 20 mg QD | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 0.83 Hour |
| Part 1: GSK525762 30 mg QD MM | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 1.26 Hour |
| Part 1: GSK525762 40 mg QD | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 0.50 Hour |
| Part 1: GSK525762 40 mg QD MM | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 0.78 Hour |
| Part 1: GSK525762 60 mg QD AML | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 0.58 Hour |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 0.50 Hour |
| Part 1: GSK525762 60 mg QD MM | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 0.63 Hour |
| Part 1: GSK525762 75 mg QD AML | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 0.60 Hour |
| Part 1: GSK525762 80 mg QD | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 0.50 Hour |
| Part 1: GSK525762 80 mg QD AML | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 0.98 Hour |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 1.06 Hour |
| Part 1: GSK525762 100 mg QD AML | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 2.00 Hour |
| Part 1: GSK525762 120 mg QD AML | Part 1: Tmax of GSK525762 Following Repeat Dose Administration | 2.33 Hour |
Secondary
Part 1: Trough Concentration (Ctau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis. GSK3529246 is a metabolite of GSK525762.
Time frame: Week 2 Day 7: Pre-dose on Days 4, 6 and 7
Population: PK Population. Only those participants with data available at the specified data points were analyzed. Plasma samples were not collected for analysis of GSK3529246 (active metabolite) for cohort GSK525762 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD AML, 80 mg QD, 80 mg QD AML, 120 mg QD AML.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 30 mg QD MM | Part 1: Trough Concentration (Ctau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 22.48 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36.13 |
| Part 1: GSK525762 40 mg QD MM | Part 1: Trough Concentration (Ctau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 13.26 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Trough Concentration (Ctau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 64.57 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 77.46 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Trough Concentration (Ctau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 40.42 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 43.96 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Trough Concentration (Ctau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 76.23 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 62.65 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Trough Concentration (Ctau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 28.29 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 94.01 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Trough Concentration (Ctau) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 178.76 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 69.25 |
Secondary
Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration
Plasma samples for PK analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Week 2 Day 7: Pre-dose on Days 4, 6 and 7
Population: PK Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 0.91 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 10 mg QD | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 3.90 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 20 mg QD | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 3.76 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 30 mg QD MM | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 4.88 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 78.94 |
| Part 1: GSK525762 40 mg QD | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 8.12 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 40 mg QD MM | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 2.26 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 114.63 |
| Part 1: GSK525762 60 mg QD AML | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 32.85 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 88.47 |
| Part 1: GSK525762 60 mg QD NHL | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 5.99 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41.92 |
| Part 1: GSK525762 60 mg QD MM | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 0.03 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 128.56 |
| Part 1: GSK525762 75 mg QD AML | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 13.21 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 102.35 |
| Part 1: GSK525762 80 mg QD | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 2.08 Nanograms per milliliter (ng/mL) | — |
| Part 1: GSK525762 80 mg QD AML | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 15.77 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 123.78 |
| Part 1: GSK525762 80 mg QD NHL | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 2.25 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 92.05 |
| Part 1: GSK525762 100 mg QD AML | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 42.18 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 139.74 |
| Part 1: GSK525762 120 mg QD AML | Part 1: Trough Concentration (Ctau) of GSK525762 Following Repeat Dose Administration | 14.34 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 68.62 |
Secondary
Part 2: Apparent Central Volume of Distribution (V1/F) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. Pharmacokinetic parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach.
Time frame: Week 3 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose
Population: PK Population. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to N=0 for 80 mg QD arm within this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Apparent Central Volume of Distribution (V1/F) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 80.0 Liters | Standard Deviation 37.1 |
| Part 1: GSK525762 10 mg QD | Part 2: Apparent Central Volume of Distribution (V1/F) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 63.4 Liters | Standard Deviation 30.6 |
Secondary
Part 2: Apparent Central Volume of Distribution (V1/F) of GSK3529246 (Active Metabolite) Following Single Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. Pharmacokinetic parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach.
Time frame: Week 1 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose
Population: PK Population. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to N of 75 mg arm within this outcome measure is greater than overall N for 75 mg QD MDS \& N=0 for 80 mg QD CTCL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Apparent Central Volume of Distribution (V1/F) of GSK3529246 (Active Metabolite) Following Single Dose Administration | 80.0 Liters | Standard Deviation 37.1 |
| Part 1: GSK525762 10 mg QD | Part 2: Apparent Central Volume of Distribution (V1/F) of GSK3529246 (Active Metabolite) Following Single Dose Administration | 71.5 Liters | Standard Deviation 28.4 |
Secondary
Part 2: Apparent Central Volume of Distribution (V1/F) of GSK525762 Following Repeat Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach.
Time frame: Week 3 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose
Population: PK Population. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to N=0 for 80 mg QD arm within this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Apparent Central Volume of Distribution (V1/F) of GSK525762 Following Repeat Dose Administration | 51.5 Liters | Standard Deviation 19.5 |
| Part 1: GSK525762 10 mg QD | Part 2: Apparent Central Volume of Distribution (V1/F) of GSK525762 Following Repeat Dose Administration | 45.8 Liters | Standard Deviation 9.92 |
Secondary
Part 2: Apparent Central Volume of Distribution (V1/F) of GSK525762 Following Single Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach.
Time frame: Week 1 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose
Population: PK Population. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to N of 75 mg arm within this outcome measure is greater than overall N for 75 mg QD MDS \& N=0 for 80 mg QC CTCL arm for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Apparent Central Volume of Distribution (V1/F) of GSK525762 Following Single Dose Administration | 51.5 Liters | Standard Deviation 19.5 |
| Part 1: GSK525762 10 mg QD | Part 2: Apparent Central Volume of Distribution (V1/F) of GSK525762 Following Single Dose Administration | 47.9 Liters | Standard Deviation 8.01 |
Secondary
Part 2: Apparent Clearance (CL/F) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. Pharmacokinetic parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach.
Time frame: Week 3 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose
Population: PK Population. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to N=0 for 80 mg QD arm within this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Apparent Clearance (CL/F) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 15.9 Liters per hour | Standard Deviation 7.26 |
| Part 1: GSK525762 10 mg QD | Part 2: Apparent Clearance (CL/F) of GSK3529246 (Active Metabolite) Following Repeat Dose Administration | 14.6 Liters per hour | Standard Deviation 8.07 |
Secondary
Part 2: Apparent Clearance (CL/F) of GSK3529246 (Active Metabolite) Following Single Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK3529246 (active metabolite) were collected at the indicated time points. GSK3529246 is a metabolite of GSK525762. PK parameters were calculated by empirical Bayes estimates. GSK3529246 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach.
Time frame: Week 1 Day 1: pre-dose and at 0.5 - 2 hours, 4 - 8 hours post-dose
Population: PK Population. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to N of 75 mg arm within this outcome measure is greater than overall N for 75 mg QD MDS \& N=0 for 80 mg QC CTCL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Apparent Clearance (CL/F) of GSK3529246 (Active Metabolite) Following Single Dose Administration | 16.5 Liters per hour | Standard Deviation 7.71 |
| Part 1: GSK525762 10 mg QD | Part 2: Apparent Clearance (CL/F) of GSK3529246 (Active Metabolite) Following Single Dose Administration | 15.8 Liters per hour | Standard Deviation 6.97 |
Secondary
Part 2: Apparent Clearance (CL/F) of GSK525762 After Repeat Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach.
Time frame: Week 3 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose
Population: PK Population. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to N=0 for 80 mg QD arm within this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Apparent Clearance (CL/F) of GSK525762 After Repeat Dose Administration | 11.80 Liters per hour | Standard Deviation 3.39 |
| Part 1: GSK525762 10 mg QD | Part 2: Apparent Clearance (CL/F) of GSK525762 After Repeat Dose Administration | 9.33 Liters per hour | Standard Deviation 4.01 |
Secondary
Part 2: Apparent Clearance (CL/F) of GSK525762 After Single Dose Administration
Plasma samples for pharmacokinetic (PK) analysis of GSK525762 were collected at the indicated time points. PK parameters were calculated by empirical Bayes estimates. GSK525762 plasma concentration-time data was analyzed by Population PK methods using a non-linear mixed-effects modelling approach.
Time frame: Week 1 Day 1: pre-dose and at 0.5 - 2 hour, 4 - 8 hours post-dose
Population: PK Population. Given only one participant at 80 mg for single dose data, population PK analysis of combined data from 75 mg QD and 80 mg QD CTCL was more appropriate. Hence the single participant of 80 mg QD arm was included in 75 mg QD MDS arm which leads to N of 75 mg arm within this outcome measure is greater than overall N for 75 mg QD MDS \& N=0 for 80 mg QC CTCL arm for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Apparent Clearance (CL/F) of GSK525762 After Single Dose Administration | 11.80 Liters per hour | Standard Deviation 3.39 |
| Part 1: GSK525762 10 mg QD | Part 2: Apparent Clearance (CL/F) of GSK525762 After Single Dose Administration | 7.98 Liters per hour | Standard Deviation 3.32 |
Secondary
Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort
The effects of treatment on disease-related symptoms/quality of life was assessed using the Skindex-29 Questionnaire, which inquires about how often (Never, Rarely, Sometimes, Often, All the time) during the previous 4 weeks the participant experienced the effect described in each of 29 items divided into 3 domains: Emotional (10 items), Symptoms (7 items) and Functioning (12 items). Responses to each item are transformed to a linear scale of 100, varying from 0 (no effect) to 100 (effect experienced all the time). Skindex-29 scores were reported as three individual domain scale scores; a scale score is the mean of a participant's responses to items in a given domain. Each domain score ranges from 0 (no effect) to 100 (effect experienced all the time), higher score implies higher impact of skin disease. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is defined is post-dose visit value minus Baseline.
Time frame: Baseline (pre-dose Week1 Day1) and Week 3, Week 7, Week 10, Week 16 and Week 24
Population: All Treated Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Symptoms score, Week 24, n=2,0 | -14.29 Scores on a scale | Standard Deviation 10.102 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Symptoms score, Week 10, n=3,0 | -29.76 Scores on a scale | Standard Deviation 20.927 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Symptoms score, Week 16, n=3,0 | -8.33 Scores on a scale | Standard Deviation 19.67 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Emotional score, Week 3, n=6,1 | -5.83 Scores on a scale | Standard Deviation 15.221 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Emotional score, Week 7, n=5,0 | -19.50 Scores on a scale | Standard Deviation 22.735 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Emotional score, Week 10, n=3,0 | -44.17 Scores on a scale | Standard Deviation 26.497 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Emotional score, Week 16, n=3,0 | -10.00 Scores on a scale | Standard Deviation 10.897 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Emotional score, Week 24, n=2,0 | -18.75 Scores on a scale | Standard Deviation 1.768 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Functioning score, Week 3, n=6,1 | -1.42 Scores on a scale | Standard Deviation 7.742 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Functioning score, Week 7, n=5,0 | -13.37 Scores on a scale | Standard Deviation 23 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Functioning score, Week 10, n=3,0 | -35.67 Scores on a scale | Standard Deviation 27.82 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Functioning score, Week 16, n=3,0 | -13.45 Scores on a scale | Standard Deviation 9.788 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Functioning score, Week 24, n=2,0 | -18.84 Scores on a scale | Standard Deviation 11.919 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Symptoms score, Week 3, n=6,1 | 6.55 Scores on a scale | Standard Deviation 24.055 |
| Part 1: GSK525762 5 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Symptoms score, Week 7, n=5,0 | -2.14 Scores on a scale | Standard Deviation 18.489 |
| Part 1: GSK525762 10 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Emotional score, Week 3, n=6,1 | 9.17 Scores on a scale | — |
| Part 1: GSK525762 10 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Symptoms score, Week 3, n=6,1 | 12.50 Scores on a scale | — |
| Part 1: GSK525762 10 mg QD | Part 2: Change From Baseline in Skindex-29 Domain Scores (Emotional, Functioning and Symptoms Score) for CTCL Cohort | Functioning score, Week 3, n=6,1 | 30.87 Scores on a scale | — |
Secondary
Part 2: Duration of Response (DOR)
Duration of response is defined as the time from the first documented evidence response (CR or PR lasting 4 months for CTCL; and CR, marrow CR, CRp, Cri or PR for MDS) until the first documented disease progression or death due to any cause. Median and inter-quartile range (first quartile and third quartile) of duration of response are presented.
Time frame: Up to 36.4 weeks
Population: All treated Population. Only those participants with data available at the specified data points were analyzed. Participants with incomplete response rates were excluded from the analysis hence N=0 for 60 mg QD and 80 mg QD CTCL arms.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GSK525762 10 mg QD | Part 2: Duration of Response (DOR) | 3.29 Months |
Secondary
Part 2: Number of Participants With Dose Interruptions/Delays
Number of participants with any dose interruptions or delays is presented.
Time frame: Up to 36.4 weeks
Population: All Treated Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Dose Interruptions/Delays | 7 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Dose Interruptions/Delays | 13 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Dose Interruptions/Delays | 1 Participants |
Secondary
Part 2: Number of Participants With Dose Reductions
Number of participants with dose reductions due to any reason is presented.
Time frame: Up to 36.4 weeks
Population: All Treated Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Dose Reductions | 6 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Dose Reductions | 7 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Dose Reductions | 0 Participants |
Secondary
Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters
Blood samples were collected for the analysis of following clinical chemistry parameters: glucose, Prothrombin international normalized ratio (Pro. INR), albumin, amylase, ALT, AST, bilirubin, calcium, calcium ionized, cholesterol, creatinine, creatine kinase, lipase, potassium, magnesium, sodium, Triglycerides, ALP. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Higher grade indicates greater severity. An increase was defined as an increase relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented.
Time frame: Up to 36.4 weeks
Population: All Treated Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=7,16,1 | 6 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=7,13,1 | 2 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=7,16,1 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=7,16,1 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=7,16,1 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=7,16,1 | 2 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=7,16,1 | 2 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=5,11,1 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol, n=7,15,1 | 2 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=7,15,1 | 7 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=7,16,1 | 4 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=7,15,1 | 3 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=7,16,1 | 4 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium, n=7,16,1 | 2 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=7,15,1 | 3 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=4,13,0 | 2 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=7,16,1 | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=7,16,1 | 3 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=7,15,1 | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=7,16,1 | 4 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=7,16,1 | 14 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Pro.INR, n=4,13,0 | 5 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=7,16,1 | 9 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=7,15,1 | 6 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=7,16,1 | 10 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=7,16,1 | 2 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=7,16,1 | 9 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol, n=7,15,1 | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=5,11,1 | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=7,16,1 | 4 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=7,13,1 | 2 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=7,16,1 | 8 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium, n=7,16,1 | 7 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=7,16,1 | 6 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=7,15,1 | 6 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=7,16,1 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Albumin, n=7,16,1 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Lipase, n=7,13,1 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | AST, n=7,15,1 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALP, n=7,16,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Potassium, n=7,16,1 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Amylase, n=7,15,1 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Triglycerides, n=7,15,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Magnesium, n=7,16,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | ALT, n=7,16,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Cholesterol, n=7,15,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium Ionized, n=7,16,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Glucose, n=7,16,1 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase, n=5,11,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Calcium, n=7,16,1 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Sodium, n=7,16,1 | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Creatinine, n=7,16,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters | Bilirubin, n=7,16,1 | 0 Participants |
Secondary
Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Higher grade indicates greater severity. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any grade increase is presented.
Time frame: Up to 36.4 weeks
Population: All Treated Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets | 5 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils | 2 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin | 4 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes | 4 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils | 7 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin | 8 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes | 8 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets | 9 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes | 6 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Leukocytes | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Platelets | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Hemoglobin | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Neutrophils | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Grade Change From Baseline in Hematology Parameters | Lymphocytes | 1 Participants |
Secondary
Part 2: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: DBP and SBP
DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.0. For SBP: Grade 0 (\<=120 millimeter of mercury \[mmHg\]), Grade 1 (121-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg). For DBP: Grade 0 (\<=80 mmHg), Grade 1 (81-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg). Higher grade indicates greater severity. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. An increase is defined as an increase in grade relative to Baseline grade. Number of participants with increase to Grade 3 from Baseline is presented.
Time frame: Up to 36.4 weeks
Population: All Treated Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: DBP and SBP | DBP | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: DBP and SBP | SBP | 3 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: DBP and SBP | DBP | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: DBP and SBP | SBP | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: DBP and SBP | DBP | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Increase to Grade 3 From Baseline in Vital Signs: DBP and SBP | SBP | 1 Participants |
Secondary
Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect. AELD is adverse events leading to permanent discontinuation of study treatment.
Time frame: Up to 36.4 weeks
Population: All Treated Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs | AELD | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs | SAEs | 5 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs | Non-serious AEs | 7 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs | AELD | 9 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs | Non-serious AEs | 16 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs | SAEs | 12 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs | SAEs | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs | Non-serious AEs | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Non-serious AEs and SAEs and AELDs | AELD | 0 Participants |
Secondary
Part 2: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading)
12-lead ECGs were recorded with the participants in a supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time frame: Up to 36.4 weeks
Population: All Treated Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 6 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 11 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Clinically significant | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst-case Post-Baseline Abnormal Electrocardiogram (ECG) Findings (Investigator Reading) | Abnormal-Not Clinically significant | 1 Participants |
Secondary
Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were collected to assess glucose, ketones, occult blood, urine protein. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Any increase was defined as any increase in proportional concentrations relative to Baseline. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post Baseline with any increase is presented.
Time frame: Up to 36.4 weeks
Population: All Treated Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=7,8,1 | 2 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=5,12,1 | 4 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=6,11,1 | 0 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=7,12,1 | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=7,8,1 | 2 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=7,12,1 | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=5,12,1 | 3 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=6,11,1 | 7 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Protein, n=6,11,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Glucose, n=5,12,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Ketones, n=7,12,1 | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method | Occult blood, n=7,8,1 | 0 Participants |
Secondary
Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature
Vital signs (pulse rate and temperature) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. The clinical concern ranges were: For pulse rate (low \<60 beats per minute \[bpm\] and high \>100 bpm); For body temperature (\<=35 degrees Celsius or \>=38 degrees Celsius). Participants were counted in the worst case category that their value changed to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged, or whose value became normal, were recorded in the To Normal or No Change category. Participants were counted twice if the participant had values that changed To Low and To High, so the percentages may not add to 100%. Baseline was the most recent, non-missing value prior to or on the first study treatment dose date.
Time frame: Up to 36.4 weeks
Population: All Treated Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 2 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 3 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 3 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 1 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 5 Participants |
| Part 1: GSK525762 5 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High | 1 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High | 3 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 13 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 9 Participants |
| Part 1: GSK525762 10 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 7 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Normal or No change | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse Rate, To High | 1 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To High | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Low | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Pulse rate, To Low | 0 Participants |
| Part 1: GSK525762 20 mg QD | Part 2: Number of Participants With Worst Case Vital Signs Results Relative to Baseline: Pulse Rate and Body Temperature | Temperature, To Normal or No Change | 1 Participants |
Secondary
Part 2: Overall Survival (OS)
OS is defined as the interval of time (in months) between the date of first dose and the date of death due to any cause. Median and inter-quartile range (first quartile and third quartile) of overall survival are presented.
Time frame: Up to 36.4 weeks
Population: All Treated Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Overall Survival (OS) | NA Months |
| Part 1: GSK525762 10 mg QD | Part 2: Overall Survival (OS) | 5.85 Months |
| Part 1: GSK525762 20 mg QD | Part 2: Overall Survival (OS) | NA Months |
Secondary
Part 2: Progression Free Survival (PFS)
PFS defined as interval of time(in months) between date of first dose & earlier of date of disease progression & date of death due to any cause.Progression is participants(pt's)with MDS & with \<5% blasts:\>=50% increase in blasts to\>5% blasts/pt's with 5-10% blasts:\>=50% increase to \>10% blasts, for pt's with 10-20% blasts:\>=50% increase to \>20% blasts,for pt's with 20%-30% blasts:\>=50% increase to \>30% blasts, for CTCL progression is \>=25% increase in skin disease from Baseline/new tumors (T3\[1 or more tumors(\>=1cm diameter\]) in pt's with T1(Limited patches,papules&/or plaques covering \<10% of the skin surface;may further stratify into T1a \[patch only\] versus T1b \[plaque+-patch\]),T2(Patches,papules/plaques covering \>=10% of skin surface;may further stratify into T2a\[patch only\]versus T2b \[plaque+-patch\]) orT4(Confluence of erythema covering \>=80% body surface area) only skin disease/loss of response in those with CR/PR, increase of skin score of \> sum of nadir +50% Baseline score.
Time frame: Up to 36.4 weeks
Population: All Treated Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: GSK525762 5 mg QD | Part 2: Progression Free Survival (PFS) | 8.15 Months |
| Part 1: GSK525762 10 mg QD | Part 2: Progression Free Survival (PFS) | 2.00 Months |
| Part 1: GSK525762 20 mg QD | Part 2: Progression Free Survival (PFS) | NA Months |
Other Pre-specified
Part 1: Changes in Cardiac QT Duration Corrected for Heart Rate by Fridericia's Formula (QTcF) and Other Safety Parameters in Relation to GSK525762 PK Concentrations
Changes in QTcF and other safety parameters in relation to GSK525762 PK concentrations was planned to be analyzed.
Time frame: Up to 86.9 weeks
Population: All Treated Population. This was an other pre-specified outcome measure. Data was not analyzed and reported.
Other Pre-specified
Part 1: Number of Participants With Dose /Exposure Markers Related Change in Molecular Markers in Tumor Tissue and/or Peripheral Blood Samples
Number of participants with dose /exposure markers related change in molecular markers (e.g. gene transcription and/or expression of proteins regulated by Bromodomain \[BRD\] proteins) in tumor tissue and/or peripheral blood samples were planned to be analyzed.
Time frame: Up to 86.9 weeks
Population: All Treated Population. This was an other pre-specified outcome measure. Data was not analyzed and reported.
Other Pre-specified
Part 1: Overall Survival (OS)
Overall survival (defined as the interval of time in months between the date of first dose and the date of death due to any cause) was planned to be analyzed.
Time frame: Up to 86.9 weeks
Population: All Treated Population. This was an other pre-specified outcome measure. Data was not analyzed and reported.
Other Pre-specified
Part 2: Number of Participants With Dose /Exposure Markers Related Change in Molecular Markers in Tumor Tissue and/or Peripheral Blood Samples
Number of participants with dose /exposure markers related change in molecular markers (e.g. gene transcription and/or expression of proteins regulated by Bromodomain proteins) in tumor tissue and/or peripheral blood samples were planned to be analyzed.
Time frame: Up to 36.4 weeks
Population: All Treated Population. This was an other pre-specified outcome measure. Data was not analyzed and reported.
Other Pre-specified
Part 2: Plasma Concentrations of GSK525762 in Relationship With Safety and Efficacy Parameters Derived From Pharmacokinetic/Pharmacodynamic (PK/PD) Model
Plasma concentrations of GSK525762 in relationship with safety and efficacy parameters derived from PK/PD model was planned to be analyzed.
Time frame: Up to 36.4 weeks
Population: PK Population. This was an other pre-specified outcome measure. Data was not analyzed and reported.
Other Pre-specified
Part 2: Time to Progression (TTP) for Participants With MM
Time to Progression was planned to be analyzed.
Time frame: Up to 36.4 weeks
Population: All Treated Population. This was an other pre-specified outcome measure. Data was not analyzed and reported.