Leukemia, Myeloid, Acute
Conditions
Keywords
GSK3745417, Acute myeloid leukemia, AML, high-risk myelodysplastic syndrome, HR-MDS
Brief summary
This is a Phase 1, open label, two-part study to determine recommended phase 2 dose (RP2D) and schedule of GSK3745417 administration in participants with relapsed/refractory AML or HR-MDS.
Interventions
DRUGGSK3745417
GSK3745417 will be administered
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants must be ≥18 years of age and ≤75 years of age at the time of signing the informed consent for dose escalation and \>18 years of age at the time of signing the informed consent for the dose expansion. * Participants must be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. * Participants must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Participants with AML/HR MDS are eligible for participation in Part 1 and Part 2 if they have: 1. A diagnosis of AML according to the World Health Organization 2016 criteria with relapsed or refractory disease and ineligible for or have exhausted standard therapeutic options. 2. Have high-risk or high/very high by Revised International Prognostic Scoring System (IPSS-R) for MDS (restricted to Part 1) that has relapsed after or been refractory to prior therapy with hypomethylating agent. * Participants with a prior history of stem cell transplant (autologous and/or allogeneic) are allowed if: No clinical signs or symptoms of graft versus host disease (other than Grade 1 GVHD (\<25% skin surface affected) and the participant is off all systemic immunosuppression. (Note: topical steroids for G1 skin GVHD are permitted on study) * Participants must agree to abide by the gender specific contraceptive requirements below: Female participants are eligible to participate if they are not either pregnant or breastfeeding, and at least one of the following conditions applies: 1. Is not a woman of childbearing potential (WOCBP), or 2. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), The effectiveness of the contraceptive method will be evaluated by the investigator in relationship to the first dose of study treatment.
Exclusion criteria
* Diagnosis of acute promyelocytic leukemia (APML or t(15;17) PML-RARA fusion). Patients with biphenotypic disease are excluded. * Active central nervous system (CNS) involvement or disorder; and well controlled with ongoing treatment * Participants with Immediate life-threatening, severe complications of leukemia (sepsis, hemorrhage). * Participants with extramedullary disease as the sole site of AML * Participants with active severe or uncontrolled infection, * Participants with active autoimmune disease that has required systemic disease modifying or immunosuppressive treatment within the last 2 years. * Participants with concurrent medical condition requiring the use of systemic immunosuppressive treatment within 28 days before the first dose of study treatment. * Participants with history of vasculitis at any time prior to study treatment. * Participant with a history of other malignancies less than 2 years prior to study entry, * Participants with QT interval corrected using Fridericia's formula (QTcF) \>450 millisecond (msec) for male participants, \>470 msec for female participants, or \>480 msec for participants with bundle branch block. * Participants with recent history of allergen desensitization therapy within 4 weeks of starting study treatment. * Participants with history or evidence of cardiovascular (CV) risk history of immune myocarditis or pericarditis. * Participants with prior STING therapy. * Participants with prior solid organ transplantation. * Participants with recent prior therapy defined as follows: any non-monoclonal anti-cancer therapy within 14 days or 5 half-lives, whichever is longer, prior to start of study treatment; prior therapy with biological agents (including monoclonal antibodies) within 28 days prior to start of study treatment; any radiotherapy or major surgery within 14 days prior to start of study treatment; currently receiving investigational therapy in a clinical trial * Participants with immune-related toxicity related to prior treatment that has not resolved to Grade ≤1 (except alopecia, hearing loss or Grade ≤2 neuropathy or endocrinopathy managed with replacement therapy).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | Up to 11.3 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. A TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. |
| Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | Up to 11.3 weeks | AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (version 5.0): Grade(G) 1=Mild, G2=Moderate, G3=Severe or medically significant but not immediately life-threatening, G4=Life-threatening consequences, G5=Death related AE. |
| Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | Up to 28 days | An AE is considered to be a DLT if it is considered by the investigator to be clinically relevant and attributed (definitely, probably, or possibly) to the study intervention and meets at least 1 of the criteria listed below. Criteria for DLT included Grade(G)3 or 4 Cytokine Release Syndrome (CRS); G3 or 4 tumor lysis syndrome (TLS) that cannot be managed/ is not resolved within 72 hours (h); Liver Toxicity included Alanine aminotransferase (ALT)\>=3\* upper limit of normal (ULN), plus bilirubin\>=2\* ULN (\>35 percent \[%\] direct) or plus international normalized ratio (INR)\>1.5 (Possible Hy's law); G\>=3 non-hematologic toxicity of any duration; G\>=3 immune-related toxicity that does not resolve to G\<=1 or Baseline within 8 days despite adequate immune suppressive therapy. Any other event which in the judgment of the investigator and GSK Medical Monitor is considered to be a DLT. |
| Part 1: Number of Participants With Withdrawals Due to AEs | Up to 11.3 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. |
| Part 2: Objective Response Rate (ORR) | Up to Day 84 | Overall response rate (ORR) defined as the percentage of participants with a complete remission (CR), CR with incomplete platelet recovery (CRp), incomplete count recovery (CRi), or a partial remission (PR) as per response criteria for AML and HR-MDS. CR=The participant must achieve a morphologic leukemia-free state (\<= 5% blasts) and have no evidence of extramedullary disease. The participant must be free of all symptoms related to leukemia, have an absolute neutrophil count \>= 1\*10\^9/Liter (L) and platelet count \>=100\*10\^9/L, and be transfusion independent. CRp: Marrow response as per CR but platelet count \<100 × 10\^9/L. CRi: Marrow response as per CR but platelet count \<100\*10\^9/L or neutrophil count \<1\*10\^9/L. PR=A decrease from Baseline of at least 50% in the number of bone marrow blasts, to between 5% and 25% of the bone marrow aspirate. |
| Part 2: Number of Participants With TEAEs and TESAEs | Up to 49 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. A TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. |
| Part 2: Number of Participants With TEAEs and TESAEs by Severity Grades | Up to 49 weeks | AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to NCI-CTCAE (version 5.0): G1=Mild, G2=Moderate, G3=Severe or medically significant but not immediately life-threatening, G4=Life-threatening consequences, G5=Death related AE. |
| Part 2: Number of Participants With Dose Limiting Toxicities (DLT) | Up to 28 days | An AE is considered to be a DLT if it is considered by the investigator to be clinically relevant and attributed (definitely, probably, or possibly) to the study intervention and meets at least 1 of the criteria listed below. Criteria for DLT included Grade(G)3 or 4 Cytokine Release Syndrome (CRS); G3 or 4 TLS that cannot be managed/ is not resolved within 72 hours (h); Liver Toxicity included ALT\>=3\*upper limit of normal (ULN), plus bilirubin\>=2\*ULN (\>35% direct) or plus international normalized ratio (INR)\>1.5 (Possible Hy's law); G\>=3 non-hematologic toxicity of any duration; G\>=3 immune-related toxicity that does not resolve to G\<=1 or Baseline within 8 days despite adequate immune suppressive therapy. Any other event which in the judgment of the investigator and GSK Medical Monitor is considered to be a DLT. |
| Part 2: Number of Participants With Withdrawals Due to AEs | Up to 49 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: AUC(0-infinity) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: AUC(0-infinity) Following Administration of GSK3745417 100 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: AUC(0-infinity) Following Administration of GSK3745417 300 µg | Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 100 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 300 µg | Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 100 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 300 µg | Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 100 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 300 µg | Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Volume of Distribution (V) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Volume of Distribution (V) Following Administration of GSK3745417 100 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Volume of Distribution (V) Following Administration of GSK3745417 300 µg | Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 2: Number of Participants With AEs, SAEs and Adverse Events of Special Interest (AESIs) Leading to Dose Modification and Dose Delays | Up to 49 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. AESI includes events that were immune-related or related to Cytokine Release Syndrome or tumor lysis syndrome. |
| Part 2: Cmax Following Administration of GSK3745417 | Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 12.5 µg, 25 ug, 50 µg and 200 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3745417. |
| Part 2: AUC(0-tau) Following Administration of GSK3745417 | Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 2: AUC(0-infinity) Following Administration of GSK3745417 | Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 2: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 | Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 2: Terminal Phase Half-life (t1/2) Following Administration of Single Dose GSK3745417 | Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 2: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 | Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 2: Volume of Distribution (V) Following Administration of GSK3745417 | Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 2: AUC(0-t) Following Administration of GSK3745417 | Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12 | Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 100 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 300 µg | Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 100 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 300 µg | Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: AUC (0-tau) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: AUC (0-tau) Following Administration of GSK3745417 100 µg | Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
| Part 1: AUC (0-tau) Following Administration of GSK3745417 300 µg | Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417. |
Countries
Canada, Germany, Italy, Netherlands, Spain
Participant flow
Recruitment details
The study conducted in a staged approach consisting of 2 parts. This study was terminated due to termination of asset after Part 1. Hence, no participants were enrolled in Part 2 of the study.
Pre-assignment details
A total of 18 participants were enrolled in Part 1 of the study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Cohort 1: GSK3745417 12.5 ug Followed by 25 ug Followed by 50 ug Participants with relapsed or refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS) received GSK3745417 12.5 microgram (ug), powder for solution as intravenous (IV) injection from Days 1 to 28 (Cycle 1) followed by GSK3745417 25 ug, powder for solution as IV injection from Days 29 to 57 (Cycle 2); further followed by GSK3745417 50 ug, powder for solution as IV injection from Days 58 to 86 (Cycle 3). Each cycle was of 28 days. | 4 |
| Part 1: Cohort 2: GSK3745417 25 ug Followed by 50 ug Followed by 100 ug Participants with relapsed or refractory AML and HR-MDS received GSK3745417 25 ug, powder for solution as IV injection from Days 1 to 28 (Cycle 1) followed by GSK3745417 50 ug, powder for solution as IV injection from Days 29 to 57 (Cycle 2); further followed by GSK3745417 100 ug, powder for solution as IV injection from Days 58 to 86 (Cycle 3). Each cycle was of 28 days. | 3 |
| Part 1: Cohort 3: GSK3745417 50 ug Followed by 100 ug Followed by 200 ug Participants with relapsed or refractory AML and HR-MDS received GSK3745417 50 ug, powder for solution as IV injection from Days 1 to 28 (Cycle 1) followed by GSK3745417 100 ug, powder for solution as IV injection from Days 29 to 57 (Cycle 2); further followed by GSK3745417 200 ug, powder for solution as IV injection from Days 58 to 86 (Cycle 3). Each cycle was of 28 days. | 3 |
| Part 1: Cohort 4: GSK3745417 100 ug Followed by 200 ug Followed by 300 ug Participants with relapsed or refractory AML and HR-MDS received GSK3745417 100 ug, powder for solution as IV injection from Days 1 to 28 (Cycle 1) followed by GSK3745417 200 ug, powder for solution as IV injection from Days 29 to 57 (Cycle 2); further followed by GSK3745417 300 ug, powder for solution as IV injection from Days 58 to 86 (Cycle 3). Each cycle was of 28 days. | 3 |
| Part 1: Cohort 5: GSK3745417 200 ug Followed by 300 ug Followed by 300 ug Participants with relapsed or refractory AML and HR-MDS received GSK3745417 200 ug, powder for solution as IV injection from Days 1 to 28 (Cycle 1) followed by GSK3745417 300 ug, powder for solution as IV injection from Days 29 to 57 (Cycle 2); further followed by GSK3745417 300 ug, powder for solution as IV injection from Days 58 to 86 (Cycle 3). Each cycle was of 28 days. | 5 |
| Part 2: GSK3745417 Participants in Part 2 with relapsed or refractory AML and HR-MDS were planned to receive GSK3745417 starting at the maximum tolerated dose determined from Part 1 of the study. | 0 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Part 1: Cohort 1: 12.5 ug (Days 1 to 28) | Death | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Cohort 1: 25 ug (Days 29 to 57) | Death | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Cohort 1: 50 ug (Days 58 to 86) | Death | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Cohort 2: 100 ug (Days 58 to 86) | Death | 0 | 1 | 0 | 0 | 0 | 0 |
| Part 1: Cohort 2: 25 ug (Days 1 to 28) | Death | 0 | 1 | 0 | 0 | 0 | 0 |
| Part 1: Cohort 3: 100 ug (Days 29 to 57) | Death | 0 | 0 | 1 | 0 | 0 | 0 |
| Part 1: Cohort 3: 100 ug (Days 29 to 57) | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
| Part 1: Cohort 3: 200 ug (Days 58 to 86) | Death | 0 | 0 | 1 | 0 | 0 | 0 |
| Part 1: Cohort 4:100 ug (Days 1 to 28) | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1: Cohort 4: 200 ug (Days 29 to 57) | Death | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1: Cohort 4: 300 ug (Days 58 to 86) | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1: Cohort 5: 200 ug (Days 1 to 28) | Death | 0 | 0 | 0 | 0 | 3 | 0 |
| Part 1: Cohort 5: 200 ug (Days 1 to 28) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 1: Cohort 5: 300 ug (Days 58 to 86) | Death | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1: Cohort 1: GSK3745417 12.5 ug Followed by 25 ug Followed by 50 ug | Part 1: Cohort 2: GSK3745417 25 ug Followed by 50 ug Followed by 100 ug | Part 1: Cohort 3: GSK3745417 50 ug Followed by 100 ug Followed by 200 ug | Part 1: Cohort 4: GSK3745417 100 ug Followed by 200 ug Followed by 300 ug | Part 1: Cohort 5: GSK3745417 200 ug Followed by 300 ug Followed by 300 ug | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 44.0 YEARS STANDARD_DEVIATION 17.11 | 71.3 YEARS STANDARD_DEVIATION 4.73 | 69.7 YEARS STANDARD_DEVIATION 4.04 | 53.7 YEARS STANDARD_DEVIATION 15.31 | 67.0 YEARS STANDARD_DEVIATION 7.07 | 60.8 YEARS STANDARD_DEVIATION 14.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 5 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex/Gender, Customized Female | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 8 Participants |
| Sex/Gender, Customized Male | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 10 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 2 / 6 | 1 / 6 | 2 / 8 | 5 / 8 | 1 / 2 | 0 / 0 |
| other Total, other adverse events | 3 / 4 | 5 / 6 | 5 / 6 | 7 / 8 | 8 / 8 | 2 / 2 | 0 / 0 |
| serious Total, serious adverse events | 4 / 4 | 4 / 6 | 1 / 6 | 5 / 8 | 5 / 8 | 1 / 2 | 0 / 0 |
Outcome results
Primary
Part 1: Number of Participants With Dose Limiting Toxicities (DLT)
An AE is considered to be a DLT if it is considered by the investigator to be clinically relevant and attributed (definitely, probably, or possibly) to the study intervention and meets at least 1 of the criteria listed below. Criteria for DLT included Grade(G)3 or 4 Cytokine Release Syndrome (CRS); G3 or 4 tumor lysis syndrome (TLS) that cannot be managed/ is not resolved within 72 hours (h); Liver Toxicity included Alanine aminotransferase (ALT)\>=3\* upper limit of normal (ULN), plus bilirubin\>=2\* ULN (\>35 percent \[%\] direct) or plus international normalized ratio (INR)\>1.5 (Possible Hy's law); G\>=3 non-hematologic toxicity of any duration; G\>=3 immune-related toxicity that does not resolve to G\<=1 or Baseline within 8 days despite adequate immune suppressive therapy. Any other event which in the judgment of the investigator and GSK Medical Monitor is considered to be a DLT.
Time frame: Up to 28 days
Population: DLT-evaluable Population included all participants who took at least 1 dose of study intervention and followed for the DLT observation period or were withdrawn within the DLT observation period due to meeting the DLT criteria.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
Primary
Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades
AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (version 5.0): Grade(G) 1=Mild, G2=Moderate, G3=Severe or medically significant but not immediately life-threatening, G4=Life-threatening consequences, G5=Death related AE.
Time frame: Up to 11.3 weeks
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 4 | 1 Participants |
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 3 | 3 Participants |
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 5 | 0 Participants |
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 4 | 0 Participants |
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 3 | 3 Participants |
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 2 | 1 Participants |
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 2 | 0 Participants |
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 1 | 0 Participants |
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 1 | 0 Participants |
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 5 | 0 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 2 | 2 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 1 | 0 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 3 | 1 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 4 | 1 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 5 | 2 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 1 | 1 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 2 | 0 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 3 | 1 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 4 | 0 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 5 | 2 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 4 | 2 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 3 | 0 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 1 | 0 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 5 | 0 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 3 | 1 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 2 | 2 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 1 | 1 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 4 | 0 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 5 | 0 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 2 | 0 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 2 | 0 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 3 | 3 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 2 | 0 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 5 | 1 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 4 | 0 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 1 | 1 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 1 | 1 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 5 | 1 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 4 | 0 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 3 | 6 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 2 | 1 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 4 | 2 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 5 | 1 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 1 | 0 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 1 | 1 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 3 | 2 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 5 | 1 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 4 | 1 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 3 | 3 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 2 | 1 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 1 | 0 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 5 | 0 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 2 | 0 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 3 | 1 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 5 | 0 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 2 | 0 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 4 | 1 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 3 | 1 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TEAEs, Grade 1 | 0 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades | TESAEs, Grade 4 | 0 Participants |
Primary
Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. A TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state.
Time frame: Up to 11.3 weeks
Population: Safety Population included all participants who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TEAEs | 4 Participants |
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TESAEs | 4 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TEAEs | 6 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TESAEs | 4 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TEAEs | 5 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TESAEs | 1 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TEAEs | 8 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TESAEs | 5 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TEAEs | 8 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TESAEs | 5 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TEAEs | 2 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs) | TESAEs | 1 Participants |
Primary
Part 1: Number of Participants With Withdrawals Due to AEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
Time frame: Up to 11.3 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Number of Participants With Withdrawals Due to AEs | 0 Participants |
| Part 1: GSK3745417 25 ug | Part 1: Number of Participants With Withdrawals Due to AEs | 0 Participants |
| Part 1: GSK3745417 50 ug | Part 1: Number of Participants With Withdrawals Due to AEs | 0 Participants |
| Part 1: GSK3745417 100 ug | Part 1: Number of Participants With Withdrawals Due to AEs | 0 Participants |
| Part 1: GSK3745417 200 ug | Part 1: Number of Participants With Withdrawals Due to AEs | 0 Participants |
| Part 1: GSK3745417 300 ug | Part 1: Number of Participants With Withdrawals Due to AEs | 0 Participants |
Primary
Part 2: Number of Participants With Dose Limiting Toxicities (DLT)
An AE is considered to be a DLT if it is considered by the investigator to be clinically relevant and attributed (definitely, probably, or possibly) to the study intervention and meets at least 1 of the criteria listed below. Criteria for DLT included Grade(G)3 or 4 Cytokine Release Syndrome (CRS); G3 or 4 TLS that cannot be managed/ is not resolved within 72 hours (h); Liver Toxicity included ALT\>=3\*upper limit of normal (ULN), plus bilirubin\>=2\*ULN (\>35% direct) or plus international normalized ratio (INR)\>1.5 (Possible Hy's law); G\>=3 non-hematologic toxicity of any duration; G\>=3 immune-related toxicity that does not resolve to G\<=1 or Baseline within 8 days despite adequate immune suppressive therapy. Any other event which in the judgment of the investigator and GSK Medical Monitor is considered to be a DLT.
Time frame: Up to 28 days
Population: Safety Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Primary
Part 2: Number of Participants With TEAEs and TESAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. A TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state.
Time frame: Up to 49 weeks
Population: Safety Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Primary
Part 2: Number of Participants With TEAEs and TESAEs by Severity Grades
AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to NCI-CTCAE (version 5.0): G1=Mild, G2=Moderate, G3=Severe or medically significant but not immediately life-threatening, G4=Life-threatening consequences, G5=Death related AE.
Time frame: Up to 49 weeks
Population: Safety Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Primary
Part 2: Number of Participants With Withdrawals Due to AEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
Time frame: Up to 49 weeks
Population: Safety Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Primary
Part 2: Objective Response Rate (ORR)
Overall response rate (ORR) defined as the percentage of participants with a complete remission (CR), CR with incomplete platelet recovery (CRp), incomplete count recovery (CRi), or a partial remission (PR) as per response criteria for AML and HR-MDS. CR=The participant must achieve a morphologic leukemia-free state (\<= 5% blasts) and have no evidence of extramedullary disease. The participant must be free of all symptoms related to leukemia, have an absolute neutrophil count \>= 1\*10\^9/Liter (L) and platelet count \>=100\*10\^9/L, and be transfusion independent. CRp: Marrow response as per CR but platelet count \<100 × 10\^9/L. CRi: Marrow response as per CR but platelet count \<100\*10\^9/L or neutrophil count \<1\*10\^9/L. PR=A decrease from Baseline of at least 50% in the number of bone marrow blasts, to between 5% and 25% of the bone marrow aspirate.
Time frame: Up to Day 84
Population: Safety Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Secondary
Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 100 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 100 µg | DAY 1 | 73.7605 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 102.0968 |
| Part 1: GSK3745417 12.5 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 100 µg | DAY 5 | 129.1817 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 133.3992 |
| Part 1: GSK3745417 12.5 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 100 µg | DAY 8 | 88.3060 Hour*nanogram/milliliter (h*ng/mL) | — |
| Part 1: GSK3745417 12.5 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 100 µg | DAY 12 | 246.3285 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 273.1186 |
Secondary
Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 21.7427 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 57.6324 |
| Part 1: GSK3745417 12.5 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 24.5192 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 70.8547 |
| Part 1: GSK3745417 25 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 53.4229 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 75.0209 |
| Part 1: GSK3745417 25 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 18.3426 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 105.4447 |
| Part 1: GSK3745417 50 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 39.7661 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 86.7711 |
| Part 1: GSK3745417 50 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 40.3425 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 46.5663 |
| Part 1: GSK3745417 100 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 115.7833 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 86.2087 |
| Part 1: GSK3745417 100 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 269.2527 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 97.8566 |
Secondary
Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 300 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 300 µg | DAY 1 | 111.0980 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 17.4746 |
| Part 1: GSK3745417 12.5 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 300 µg | DAY 5 | 156.7682 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 21.7702 |
| Part 1: GSK3745417 12.5 ug | Part 1: Area Under the Concentration-time Curve AUC(0-t) Following Administration of GSK3745417 300 µg | DAY 8 | 177.0957 Hour*nanogram/milliliter (h*ng/mL) | — |
Secondary
Part 1: AUC(0-infinity) Following Administration of GSK3745417 100 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 100 µg | DAY 1 | 82.4501 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 122.0638 |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 100 µg | DAY 5 | 149.6791 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 171.2285 |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 100 µg | DAY 8 | 91.6906 Hour*nanogram/milliliter (h*ng/mL) | — |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 100 µg | DAY 12 | 92.8915 Hour*nanogram/milliliter (h*ng/mL) | — |
Secondary
Part 1: AUC(0-infinity) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 24.1814 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 58.7275 |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 32.1932 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 85.8221 |
| Part 1: GSK3745417 25 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 61.4040 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 89.9314 |
| Part 1: GSK3745417 25 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 19.7396 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 111.3832 |
| Part 1: GSK3745417 50 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 44.1762 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 110.0662 |
| Part 1: GSK3745417 50 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 42.2109 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 48.0113 |
| Part 1: GSK3745417 100 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 124.8946 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 103.5148 |
| Part 1: GSK3745417 100 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 302.1566 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 119.5787 |
Secondary
Part 1: AUC(0-infinity) Following Administration of GSK3745417 300 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 300 µg | DAY 1 | 113.4262 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 17.3464 |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 300 µg | DAY 5 | 161.3749 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 23.9753 |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC(0-infinity) Following Administration of GSK3745417 300 µg | DAY 8 | 179.2585 Hour*nanogram/milliliter (h*ng/mL) | — |
Secondary
Part 1: AUC (0-tau) Following Administration of GSK3745417 100 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 100 µg | DAY 1 | 75.4673 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 103.4499 |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 100 µg | DAY 5 | 129.6654 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 134.9177 |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 100 µg | DAY 8 | 88.4344 Hour*nanogram/milliliter (h*ng/mL) | — |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 100 µg | DAY 12 | 247.2046 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 272.271 |
Secondary
Part 1: AUC (0-tau) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 22.0086 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 58.5871 |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 24.4250 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 71.8245 |
| Part 1: GSK3745417 25 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 53.6275 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 75.3947 |
| Part 1: GSK3745417 25 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 18.6671 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 101.466 |
| Part 1: GSK3745417 50 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 40.4989 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 86.3765 |
| Part 1: GSK3745417 50 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 40.5395 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 46.3785 |
| Part 1: GSK3745417 100 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 116.0595 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 86.0517 |
| Part 1: GSK3745417 100 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 267.9373 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 98.1167 |
Secondary
Part 1: AUC (0-tau) Following Administration of GSK3745417 300 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 300 µg | DAY 1 | 111.2544 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 17.7235 |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 300 µg | DAY 5 | 157.0654 Hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 21.6207 |
| Part 1: GSK3745417 12.5 ug | Part 1: AUC (0-tau) Following Administration of GSK3745417 300 µg | DAY 8 | 177.2807 Hour*nanogram/milliliter (h*ng/mL) | — |
Secondary
Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 100 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 100 µg | DAY 1 | 23.4043 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 34.986 |
| Part 1: GSK3745417 12.5 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 100 µg | DAY 5 | 27.9947 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 33.7584 |
| Part 1: GSK3745417 12.5 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 100 µg | DAY 8 | 20.7000 Nanogram/milliliter (ng/mL) | — |
| Part 1: GSK3745417 12.5 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 100 µg | DAY 12 | 37.9700 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 50.5418 |
Secondary
Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 12.5 µg, 25 ug, 50 µg and 200 µg
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5
Population: Pharmacokinetic (PK) Population included all participants from the Safety Analysis Set for whom a PK sample was obtained and analyzed. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 12.5 µg, 25 ug, 50 µg and 200 µg | DAY 1 | 4.0437 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 63.1268 |
| Part 1: GSK3745417 12.5 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 12.5 µg, 25 ug, 50 µg and 200 µg | DAY 5 | 3.3922 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 76.7856 |
| Part 1: GSK3745417 25 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 12.5 µg, 25 ug, 50 µg and 200 µg | DAY 5 | 9.9633 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 50.2486 |
| Part 1: GSK3745417 25 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 12.5 µg, 25 ug, 50 µg and 200 µg | DAY 1 | 5.3407 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 18.6391 |
| Part 1: GSK3745417 50 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 12.5 µg, 25 ug, 50 µg and 200 µg | DAY 1 | 11.4244 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 15.6862 |
| Part 1: GSK3745417 50 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 12.5 µg, 25 ug, 50 µg and 200 µg | DAY 5 | 11.7986 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 12.9766 |
| Part 1: GSK3745417 100 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 12.5 µg, 25 ug, 50 µg and 200 µg | DAY 1 | 49.8671 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 25.7641 |
| Part 1: GSK3745417 100 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 12.5 µg, 25 ug, 50 µg and 200 µg | DAY 5 | 55.8182 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 32.3703 |
Secondary
Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 300 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 300 µg | DAY 1 | 60.0576 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 18.6563 |
| Part 1: GSK3745417 12.5 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 300 µg | DAY 5 | 83.6227 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 13.7291 |
| Part 1: GSK3745417 12.5 ug | Part 1: Maximum Concentration (Cmax) Following Administration of GSK3745417 300 µg | DAY 8 | 95.6000 Nanogram/milliliter (ng/mL) | — |
Secondary
Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 100 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 100 µg | DAY 1 | 1.2121 Liter/hour (L/h) | Geometric Coefficient of Variation 121.9357 |
| Part 1: GSK3745417 12.5 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 100 µg | DAY 5 | 0.6681 Liter/hour (L/h) | Geometric Coefficient of Variation 171.2285 |
| Part 1: GSK3745417 12.5 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 100 µg | DAY 8 | 1.0906 Liter/hour (L/h) | — |
| Part 1: GSK3745417 12.5 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 100 µg | DAY 12 | 0.2935 Liter/hour (L/h) | Geometric Coefficient of Variation 532.2277 |
Secondary
Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 0.5169 Liter/hour (L/h) | Geometric Coefficient of Variation 58.7275 |
| Part 1: GSK3745417 12.5 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 0.3883 Liter/hour (L/h) | Geometric Coefficient of Variation 85.8221 |
| Part 1: GSK3745417 25 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 0.4090 Liter/hour (L/h) | Geometric Coefficient of Variation 89.8847 |
| Part 1: GSK3745417 25 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 1.2669 Liter/hour (L/h) | Geometric Coefficient of Variation 110.9895 |
| Part 1: GSK3745417 50 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 1.1313 Liter/hour (L/h) | Geometric Coefficient of Variation 109.9904 |
| Part 1: GSK3745417 50 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 1.1870 Liter/hour (L/h) | Geometric Coefficient of Variation 48.4302 |
| Part 1: GSK3745417 100 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 1.5982 Liter/hour (L/h) | Geometric Coefficient of Variation 103.1281 |
| Part 1: GSK3745417 100 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 0.8532 Liter/hour (L/h) | Geometric Coefficient of Variation 140.7702 |
Secondary
Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 300 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 300 µg | DAY 1 | 2.6516 Liter/hour (L/h) | Geometric Coefficient of Variation 17.5162 |
| Part 1: GSK3745417 12.5 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 300 µg | DAY 5 | 1.8769 Liter/hour (L/h) | Geometric Coefficient of Variation 22.2726 |
| Part 1: GSK3745417 12.5 ug | Part 1: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417 300 µg | DAY 8 | 1.6736 Liter/hour (L/h) | — |
Secondary
Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 100 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 100 µg | DAY 1 | 0.1400 1/hour | Geometric Coefficient of Variation 114.8419 |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 100 µg | DAY 5 | 0.0862 1/hour | Geometric Coefficient of Variation 43.9385 |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 100 µg | DAY 8 | 0.1300 1/hour | — |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 100 µg | DAY 12 | 0.0603 1/hour | Geometric Coefficient of Variation 100.8393 |
Secondary
Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 0.0958 1/hour | Geometric Coefficient of Variation 14.0287 |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 0.0564 1/hour | Geometric Coefficient of Variation 23.4595 |
| Part 1: GSK3745417 25 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 0.0902 1/hour | Geometric Coefficient of Variation 41.2921 |
| Part 1: GSK3745417 25 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 0.1879 1/hour | Geometric Coefficient of Variation 122.94 |
| Part 1: GSK3745417 50 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 0.1614 1/hour | Geometric Coefficient of Variation 100.3767 |
| Part 1: GSK3745417 50 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 0.1233 1/hour | Geometric Coefficient of Variation 7.5634 |
| Part 1: GSK3745417 100 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 0.1106 1/hour | Geometric Coefficient of Variation 98.3724 |
| Part 1: GSK3745417 100 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 0.0924 1/hour | Geometric Coefficient of Variation 36.4027 |
Secondary
Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 300 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 300 µg | DAY 1 | 0.0978 1/hour | Geometric Coefficient of Variation 39.1392 |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 300 µg | DAY 5 | 0.1237 1/hour | Geometric Coefficient of Variation 39.151 |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417 300 µg | DAY 8 | 0.1512 1/hour | — |
Secondary
Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 100 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 100 µg | DAY 1 | 4.9494 Hour (h) | Geometric Coefficient of Variation 114.8419 |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 100 µg | DAY 5 | 8.0420 Hour (h) | Geometric Coefficient of Variation 43.9385 |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 100 µg | DAY 8 | 5.3318 Hour (h) | — |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 100 µg | DAY 12 | 11.4948 Hour (h) | Geometric Coefficient of Variation 100.8393 |
Secondary
Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 7.2332 Hour (h) | Geometric Coefficient of Variation 14.0287 |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 12.2931 Hour (h) | Geometric Coefficient of Variation 23.4595 |
| Part 1: GSK3745417 25 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 7.6835 Hour (h) | Geometric Coefficient of Variation 41.2921 |
| Part 1: GSK3745417 25 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 3.6895 Hour (h) | Geometric Coefficient of Variation 122.94 |
| Part 1: GSK3745417 50 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 4.2938 Hour (h) | Geometric Coefficient of Variation 100.3767 |
| Part 1: GSK3745417 50 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 5.6202 Hour (h) | Geometric Coefficient of Variation 7.5634 |
| Part 1: GSK3745417 100 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 6.2658 Hour (h) | Geometric Coefficient of Variation 98.3724 |
| Part 1: GSK3745417 100 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 7.4977 Hour (h) | Geometric Coefficient of Variation 36.4027 |
Secondary
Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 300 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 300 µg | DAY 1 | 7.0877 Hour (h) | Geometric Coefficient of Variation 39.1392 |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 300 µg | DAY 5 | 5.6013 Hour (h) | Geometric Coefficient of Variation 39.151 |
| Part 1: GSK3745417 12.5 ug | Part 1: Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 300 µg | DAY 8 | 4.5845 Hour (h) | — |
Secondary
Part 1: Volume of Distribution (V) Following Administration of GSK3745417 100 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 12 and 24 hours on Day 8; Pre-dose, 5 minutes, 4, 8 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 100 µg | DAY 1 | 6.8614 Liter (L) | Geometric Coefficient of Variation 41.4133 |
| Part 1: GSK3745417 12.5 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 100 µg | DAY 5 | 6.2891 Liter (L) | Geometric Coefficient of Variation 42.2982 |
| Part 1: GSK3745417 12.5 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 100 µg | DAY 8 | 7.0024 Liter (L) | — |
| Part 1: GSK3745417 12.5 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 100 µg | DAY 12 | 5.4797 Liter (L) | Geometric Coefficient of Variation 38.0866 |
Secondary
Part 1: Volume of Distribution (V) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30 and 45 minutes, 1, 2, 4, 6, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 5
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 5.1242 Liter (L) | Geometric Coefficient of Variation 62.5343 |
| Part 1: GSK3745417 12.5 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 7.9543 Liter (L) | Geometric Coefficient of Variation 44.7917 |
| Part 1: GSK3745417 25 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 4.0818 Liter (L) | Geometric Coefficient of Variation 48.7367 |
| Part 1: GSK3745417 25 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 6.1162 Liter (L) | Geometric Coefficient of Variation 15.1427 |
| Part 1: GSK3745417 50 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 6.2318 Liter (L) | Geometric Coefficient of Variation 23.2325 |
| Part 1: GSK3745417 50 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 6.7901 Liter (L) | Geometric Coefficient of Variation 18.9568 |
| Part 1: GSK3745417 100 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 1 | 7.2915 Liter (L) | Geometric Coefficient of Variation 35.8656 |
| Part 1: GSK3745417 100 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 12.5 µg, 25 µg, 50 µg and 200 µg | DAY 5 | 6.0176 Liter (L) | Geometric Coefficient of Variation 30.5236 |
Secondary
Part 1: Volume of Distribution (V) Following Administration of GSK3745417 300 µg
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 1; Pre-dose, 5 minutes, 1, 4, 8, 12, 24 hours on Day 5; Pre-dose, 5 minutes, 4, 8, 24 hours on Day 8
Population: Pharmacokinetic (PK) Population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the 'Overall Number of Participants Analyzed' field. 'Number Analyzed' signifies participants evaluable for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: GSK3745417 12.5 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 300 µg | DAY 1 | 7.9354 Liter (L) | Geometric Coefficient of Variation 16.5438 |
| Part 1: GSK3745417 12.5 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 300 µg | DAY 5 | 6.6325 Liter (L) | Geometric Coefficient of Variation 29.824 |
| Part 1: GSK3745417 12.5 ug | Part 1: Volume of Distribution (V) Following Administration of GSK3745417 300 µg | DAY 8 | 4.5465 Liter (L) | — |
Secondary
Part 2: AUC(0-infinity) Following Administration of GSK3745417
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Secondary
Part 2: AUC(0-tau) Following Administration of GSK3745417
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Secondary
Part 2: AUC(0-t) Following Administration of GSK3745417
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Secondary
Part 2: Cmax Following Administration of GSK3745417
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Secondary
Part 2: Number of Participants With AEs, SAEs and Adverse Events of Special Interest (AESIs) Leading to Dose Modification and Dose Delays
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. AESI includes events that were immune-related or related to Cytokine Release Syndrome or tumor lysis syndrome.
Time frame: Up to 49 weeks
Population: Safety Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Secondary
Part 2: Systemic Clearance of Parent Drug (CL) Following Administration of GSK3745417
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Secondary
Part 2: Terminal Phase Elimination Rate Constant (Lambda Z) Following Administration of GSK3745417
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Secondary
Part 2: Terminal Phase Half-life (t1/2) Following Administration of Single Dose GSK3745417
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.
Secondary
Part 2: Volume of Distribution (V) Following Administration of GSK3745417
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3745417.
Time frame: Pre-dose, 5, 15, 30, 45 minutes, 1, 2, 4, 6, 8, 12 and 24 hours on Day 1; Predose on Day 4; Pre-dose and 5 minutes, 4, 8, 24 hours on Day 5; Predose and 4, 8, 12 and 24 hours on Day 8; Pre-dose, 1, 4, 8, 12 and 24 hours on Day 12
Population: Pharmacokinetic (PK) Population. No participants were enrolled in Part 2 of the study. Hence, data was not collected for Part 2 of the study.