Infection, Human Immunodeficiency Virus
Conditions
Keywords
HIV, naive, Phase II, integrase inhibitor, GSK1265744, newly diagnosed, pharmacokinetics, AIDS, integrase, HIV Infections, Treatment naive
Brief summary
The purpose of this randomized, double-blinded study is to test the safety of GSK1265744 and how well it works on reducing the amount of HIV in the blood. It will also look at how people react to and how a human body uses GSK1265744. This study will compare the effects of GSK1265744 and placebo. The study will consist of 1 or 2 parts to look at doses of GSK1265744. About 8 people will take part in Part 1 of the study receiving dose A. If additional dosing information is needed after Part 1, about 6 people will take part in Part 2 of the study receiving dose B.
Interventions
DRUGGSK1265744 30mg
GSK1265744 30 mg
DRUGPlacebo
Placebo to match GSK1265744
DRUGGSK1265744 5mg
GSK1265744 5mg
Sponsors
Shionogi
GlaxoSmithKline
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
A subject will be eligible for inclusion in this study only if all of the following criteria apply: * Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent. * A female subject is eligible to participate if she is of non-childbearing potential, defined as: * Pre-menopausal females with a documented bilateral oophorectomy, tubal ligation or hysterectomy; or * Postmenopausal defined as 12 months of spontaneous amenorrhea. A follicle stimulating hormone level will be performed to confirm post-menopausal status. For this study, FSH levels \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory. * Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 14 days after the last dose of study medication. * CD4+ cell count greater than or equal to 200 cells/mm3 and plasma HIV-1 RNA greater than or equal to 5000 copies/mL at Screening. * No current antiretroviral therapy and have not received any in the 12 weeks prior to first dose. * For subjects who have received antiretroviral treatment in the past, adequate treatment options to construct HAART therapy with at least 3 active antiretrovirals for Optimized Therapy, as selected by the Investigator. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion criteria
A subject will not be eligible for inclusion in this study if any of the following criteria apply: * A positive screening Hepatitis B surface antigen; positive screening hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid (RNA) on subsequent testing. If the hepatitis C antibody is positive but the HCV RNA is undetectable, the subject may be included in the study. * AST and ALT \> 3ULN at Screening. A single repeat is allowed for eligibility determination. * Inadequate renal function at Screening, defined as either a serum creatinine \>1.5 mg/dL or a calculated creatinine clearance (CrCl) ≤ 50 mL/min. A single repeat serum creatinine is allowed to determine eligibility. * Any acute laboratory abnormality at screening which, in the opinion of the investigator, should preclude the subject's participation in the study of an investigational compound. Any grade 4 laboratory abnormality at screening, with the exception of CPK, will exclude a subject from study participation unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat is allowed for eligibility determination. * A positive drug screen at screening and baseline. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine or PCP. * History of regular alcohol consumption, defined as an average weekly intake of \>14 drinks for males or \>7 drinks for females, within 6 months of Screening. Note: One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits. * Any condition (including alcohol or drug abuse) which, in the opinion of the investigator, could interfere with the subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject. * Prior treatment with an integrase inhibitor (greater than or equal to 1 dose). * Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or anticipated need for such treatment within the study. * Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration. * Treatment with any vaccine within 30 days prior to receiving study medication. * An active Center for Disease Control and Prevention (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial. * Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing. * Lactating females. * Use of multivitamins or antacids within 24 hours prior to the first dose of investigational product. * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled. Note: Study medications refer to GSK1265744 or placebo. * The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. * History of clinically relevant pancreatitis or hepatitis within the previous 6 months. * Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Electrocardiogram (ECG) Parameters | Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10 | All ECGs were obtained after a minimum 10 minute rest in a semi-supine position. The 12-lead ECGs were obtained at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10 using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and Bazett's correction (QTcB) and Fridericia correction (QTcF) intervals. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin | Baseline (Day 1) and Day 3, 7, 10 | Blood samples for assessment of hematology parameter of mean corpuscle hemoglobin was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Hematology Parameters: Mean Corpuscle Volume | Baseline (Day 1) and Day 3, 7, 10 | Blood samples for assessment of hematology parameter of mean corpuscle volume was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Hematology Parameters: Platelet Count | Baseline (Day 1) and Day 3, 7, 10 | Blood samples for assessment of hematology parameter of platelet count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Hematology Parameters: Red Blood Cell Count | Baseline (Day 1) and Day 3, 7, 10 | Blood samples for assessment of hematology parameter of red blood cell count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Hematology Parameters: Reticulocytes | Baseline (Day 1) and Day 3, 7, 10 | Blood samples for assessment of hematology parameter of reticulocytes was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Baseline (Day 1) and Day 3, 7, 10 | Blood samples for assessment of clinical chemistry parameters of albumin and total protein was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Baseline (Day 1) and Day 3, 7, 10 | Blood samples for assessment of clinical chemistry parameters of alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase and lipase was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Baseline (Day 1) and Day 3, 7, 10 | Blood samples for assessment of clinical chemistry parameters of direct bilirubin, total bilirubin, calcium, cholesterol, creatinine, glucose, HDL cholesterol direct, LDL cholesterol calculation, triglycerides,Urea/BUN was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Baseline (Day 1) and Day 3, 7, 10 | Blood samples for assessment of clinical chemistry parameters of chloride, carbon dioxide content/bicarbonate, magnesium, sodium and potassium was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Number of Participants With Urinalysis Data | Day 1 to Day 10 | Samples for urinalysis assessment was collected on Day 1, Day 3 and Day 10. Urinalysis parameters included urine bilirubin, urine occult blood, urine glucose, urine ketones, urine nitrite, urine pH, urine protein, urine specific gravity and urine leukocyte esterase test for detecting white blood cell. |
| Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10 | Systolic and diastolic blood pressure was measured at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Vital Sign: Heart Rate | Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10 | Heart rate was measured at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Plasma Human Immunodeficiency Virus (HIV-1) Ribonucleic Acid (RNA) to Day 11 | Baseline (Day 1) and Day 11 | Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a lower limit of detection (LLOD) of 50 copies/milliliter (mL) (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| GSK1265744 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments(AUC[0-24]) | Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose) | Blood samples for PK analysis of AUC(0-24) of GSK1265744 was collected on Day 1 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. |
| GSK1265744 PK Parameters Following Dose Administration on Day 1: Concentration at 24 Hours Post Dose (C24) | Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose) | Blood samples for PK analysis of C24 of GSK1265744 was collected on Day 1 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. |
| GSK1265744 PK Parameters Following Dose Administration on Day 10: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) | Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose) | Blood samples for PK analysis of C24 of GSK1265744 was collected on Day 10 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. |
| GSK1265744 PK Parameters Following Dose Administration on Day 10: Predose Concentration (C0), Concentration at End of Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin) | Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose) | Blood samples for PK analysis of C0, Ctau and Cmin of GSK1265744 was collected on Day 10 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. |
| GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Maximum Observed Concentration (Cmax) | Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10 | Blood samples for PK analysis of Cmax of GSK1265744 was collected at pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10. Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. |
| GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Time to Cmax (Tmax) | Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10 | Blood samples for PK analysis of tmax of GSK1265744 was collected at pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10. Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. |
| GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Terminal Half-life (t1/2) and Absorption Lag Time (Tlag) | Day 1 and Day 10 | PK sampling was planned to be collected up to 24 hours only on Day 1 and Day 10. The data for this outcome measure was however not collected. |
| GSK1265744 PK Parameters Following Last Repeat Administration on Day 10: Apparent Clearance Following Oral Dosing (CL/F) | Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose) | Blood samples for PK analysis of CL/F of GSK1265744 was collected on Day 10 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. |
| Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 to Day 11 | An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, medically significant or is associated with liver injury and impaired liver function. |
| Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Baseline (Day 1) and Day 3, 7, 10 | Blood samples for assessment of hematology parameters of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC- absolute neutrophil count) and white blood cell count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Change From Baseline in Hematology Parameters: Hemoglobin | Baseline (Day 1) and Day 3, 7, 10 | Blood samples for assessment of hematology parameter of hemoglobin was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma HIV-1 RNA to Nadir Over 11 Days | Baseline (Day 1) and Day 11 | Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Nadir was the maximum change from Baseline in plasma HIV-1 RNA. Baseline was defined at Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Plasma HIV-1 RNA Rate of Decline (Slope) Over 11 Days | Up to Day 10 | Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Estimated mean rate of decline (i.e., slope of day) with corresponding 90% confidence interval was provided for each treatment. |
| Number of Participants With HIV-1 RNA<400 Copies/mL | Up to Day 11 | Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Only categories with data available at the indicated time points have been presented. Categories with null values for all the arms have not been presented. |
| Number of Participants With HIV-1 RNA<50 Copies/mL | Up to Day 11 | Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Only categories with data available at the indicated time points have been presented. Categories with null values for all the arms have not been presented. |
| Change From Baseline in CD4+ Cell Count to Day 11 | Baseline (Day 1) and Day 11 | Whole venous blood samples was obtained from each participant for the analysis of lymphocyte subsets by flow cytometry on Day 1 and Day 11. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
| Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration | Day 1 24 hours (Day 2), Pre-dose on Days 3, 4, 7, 8, 9 and 10 | Steady state is said to be reached, when the pre-dose concentration slope estimate is close to zero. The data for pre-dose concentration on Day 1 24 hours (Day 2) through Day 10 has been presented. |
| Accumulation Ratios for AUC, Cmax, and Ctau | Days 1 and 10 | The accumulation ratio was calculated as the ratio of AUC(0-τ), Cmax, and Ctau on Day 10 to AUC(0-24), Cmax, and C24 on Day 1 for each participant. The ratio of geometric least square means of each parameter on Day 10 to Day 1 was presented along with 90% confidence interval. |
| Day 1 AUC(0-24) at Different Doses for the Assessment of Dose Proportionality Using Power Model | Day 1 | Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following single dose administration on Day 1 (AUC\[0-24\]) using the power model. The mean slope and corresponding 90% confidence interval has been presented. |
| Day 1 Cmax and C24 at Different Doses for the Assessment of Dose Proportionality Using Power Model | Day 1 | Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following single dose administration on Day 1 (Cmax, and C24) using the power model. The mean slope and corresponding 90% confidence interval has been presented. |
| Day 10 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality Using Power Model | Day 10 | Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following a repeat dose administration on Day 10 (AUC\[0-tau\]) using the power model. The mean slope and corresponding 90% confidence interval has been presented. |
| Day 10 Cmax, C0 and Ctau at Different Doses for the Assessment of Dose Proportionality Using Power Model | Day 10 | Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following a repeat dose administration on Day 10 (Cmax, Ctau and C0) using the power model. The mean slope and corresponding 90% confidence interval has been presented. |
| Change From Baseline in Plasma HIV-1 RNA | Baseline (Day 1 pre-dose) and Day 1 (post dose), 2, 3, 4, 7, 8, 9, 10 | Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA were collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Baseline was defined at Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 4 centers in the United States from 09 June 2009 to 13 August 2009.
Pre-assignment details
A total of 9 participants were randomized in the current study to receive 5 milligrams (mg) of GSK1265744 or Placebo. A total of 8 participants were previously randomized in study ITZ111451 part C HIV cohort, NCT00659191 to receive 30 mg of GSK1265744 once daily.
Participants by arm
| Arm | Count |
|---|---|
| GSK1265744 30 mg GSK1265744 30 mg once daily was previously studied in study ITZ111451 part C HIV cohort, NCT00659191. Eligible participants received repeat doses of GSK1265744 30 mg (6x5 mg) oral tablets once daily for 10 days. | 8 |
| GSK1265744 5 mg Eligible participants received double-blind GSK1265744 5 mg oral tablet once daily for 10 days. | 7 |
| Placebo Eligible participants received double-blind matching Placebo oral tablet once daily for 10 days. | 2 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| ITZ111451 | Adverse Event | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | GSK1265744 30 mg | GSK1265744 5 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Customized 27 to 51 Years | 8 Participants | 7 Participants | 2 Participants | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 5 Participants | 2 Participants | 15 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 2 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 | 0 / 2 | 0 / 8 |
| other Total, other adverse events | 4 / 8 | 0 / 7 | 2 / 2 | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 | 0 / 2 | 0 / 8 |
Outcome results
Primary
Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein
Blood samples for assessment of clinical chemistry parameters of albumin and total protein was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 3, 7, 10
Population: Safety Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Albumin, Day 3 | 0.16 Grams per deciliter | Standard Deviation 0.162 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Albumin, Day 7 | 0.08 Grams per deciliter | Standard Deviation 0.117 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Albumin, Day 10 | 0.06 Grams per deciliter | Standard Deviation 0.098 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Total protein, Day 3 | 0.24 Grams per deciliter | Standard Deviation 0.447 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Total protein, Day 7 | 0.03 Grams per deciliter | Standard Deviation 0.294 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Total protein, Day 10 | -0.10 Grams per deciliter | Standard Deviation 0.342 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Total protein, Day 7 | 0.10 Grams per deciliter | Standard Deviation 0.424 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Albumin, Day 3 | 0.00 Grams per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Total protein, Day 3 | 0.05 Grams per deciliter | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Albumin, Day 7 | 0.05 Grams per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Total protein, Day 10 | 0.10 Grams per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein | Albumin, Day 10 | 0.15 Grams per deciliter | Standard Deviation 0.071 |
Primary
Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase
Blood samples for assessment of clinical chemistry parameters of alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase and lipase was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 3, 7, 10
Population: Safety Population. Only those participants available at the indicated time points were analyzed. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alanine amino transferase, Day 7 | -0.2 Units per liter | Standard Deviation 4.02 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Aspartate amino transferase, Day 10 | 0.4 Units per liter | Standard Deviation 5.32 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alkaline phosphatase, Day 7 | 0.5 Units per liter | Standard Deviation 3.89 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Creatine kinase, Day 3 | -0.1 Units per liter | Standard Deviation 11.42 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alanine amino transferase, Day 10 | 2.0 Units per liter | Standard Deviation 4.12 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Creatine kinase, Day 7 | 27.7 Units per liter | Standard Deviation 77.11 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alanine amino transferase, Day 3 | 2.9 Units per liter | Standard Deviation 6.41 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Creatine kinase, Day 10 | 20.6 Units per liter | Standard Deviation 42.97 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Aspartate amino transferase, Day 3 | -1.0 Units per liter | Standard Deviation 4.28 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Lipase, Day 3 | 0.9 Units per liter | Standard Deviation 8.91 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alkaline phosphatase, Day 10 | -2.4 Units per liter | Standard Deviation 6.55 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Lipase, Day 7 | -0.9 Units per liter | Standard Deviation 17.22 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Aspartate amino transferase, Day 7 | -1.0 Units per liter | Standard Deviation 3.52 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Lipase, Day 10 | 0.3 Units per liter | Standard Deviation 14.42 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alkaline phosphatase, Day 3 | 1.6 Units per liter | Standard Deviation 3.1 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Lipase, Day 10 | -2.0 Units per liter | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alkaline phosphatase, Day 3 | -3.5 Units per liter | Standard Deviation 4.95 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alkaline phosphatase, Day 7 | -5.0 Units per liter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alkaline phosphatase, Day 10 | -4.0 Units per liter | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alanine amino transferase, Day 3 | -4.0 Units per liter | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alanine amino transferase, Day 7 | -1.5 Units per liter | Standard Deviation 9.19 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Alanine amino transferase, Day 10 | -2.5 Units per liter | Standard Deviation 7.78 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Aspartate amino transferase, Day 3 | -2.0 Units per liter | Standard Deviation 8.49 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Aspartate amino transferase, Day 7 | -3.5 Units per liter | Standard Deviation 7.78 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Aspartate amino transferase, Day 10 | -2.0 Units per liter | Standard Deviation 5.66 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Creatine kinase, Day 3 | -29.5 Units per liter | Standard Deviation 10.61 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Creatine kinase, Day 7 | -48.0 Units per liter | Standard Deviation 42.43 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Creatine kinase, Day 10 | -40.5 Units per liter | Standard Deviation 43.13 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Lipase, Day 3 | 4.0 Units per liter | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase | Lipase, Day 7 | -1.0 Units per liter | Standard Deviation 8.49 |
Primary
Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium
Blood samples for assessment of clinical chemistry parameters of chloride, carbon dioxide content/bicarbonate, magnesium, sodium and potassium was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 3, 7, 10
Population: Safety population. Only those participants available at the indicated time points were analyzed. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Carbon dioxide content/Bicarbonate, Day 7 | -1.3 Milliequivalents per liter | Standard Deviation 1.63 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Potassium, Day 10 | 0.07 Milliequivalents per liter | Standard Deviation 0.368 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Chloride, Day 7 | -0.2 Milliequivalents per liter | Standard Deviation 2.79 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Magnesium, Day 3 | -0.04 Milliequivalents per liter | Standard Deviation 0.098 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Carbon dioxide content/Bicarbonate, Day 10 | 0.6 Milliequivalents per liter | Standard Deviation 2.76 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Magnesium, Day 7 | -0.00 Milliequivalents per liter | Standard Deviation 0.089 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Carbon dioxide content/Bicarbonate, Day 3 | -0.9 Milliequivalents per liter | Standard Deviation 2.41 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Magnesium, Day 10 | -0.04 Milliequivalents per liter | Standard Deviation 0.098 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Potassium, Day 3 | 0.20 Milliequivalents per liter | Standard Deviation 0.2 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Sodium, Day 3 | -0.4 Milliequivalents per liter | Standard Deviation 1.62 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Chloride, Day 10 | -0.7 Milliequivalents per liter | Standard Deviation 2.69 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Sodium, Day 7 | 0.3 Milliequivalents per liter | Standard Deviation 2.5 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Potassium, Day 7 | 0.00 Milliequivalents per liter | Standard Deviation 0.245 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Sodium, Day 10 | -0.4 Milliequivalents per liter | Standard Deviation 1.62 |
| GSK1265744 5 mg | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Chloride, Day 3 | 0.0 Milliequivalents per liter | Standard Deviation 0.82 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Sodium, Day 10 | 0.5 Milliequivalents per liter | Standard Deviation 2.12 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Chloride, Day 3 | 2.0 Milliequivalents per liter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Chloride, Day 7 | 2.0 Milliequivalents per liter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Chloride, Day 10 | 2.0 Milliequivalents per liter | Standard Deviation 4.24 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Carbon dioxide content/Bicarbonate, Day 3 | -1.0 Milliequivalents per liter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Carbon dioxide content/Bicarbonate, Day 7 | -2.0 Milliequivalents per liter | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Carbon dioxide content/Bicarbonate, Day 10 | -2.0 Milliequivalents per liter | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Potassium, Day 3 | 0.30 Milliequivalents per liter | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Potassium, Day 7 | 0.20 Milliequivalents per liter | Standard Deviation 0.283 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Potassium, Day 10 | 0.05 Milliequivalents per liter | Standard Deviation 0.212 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Magnesium, Day 3 | 0.10 Milliequivalents per liter | Standard Deviation 0 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Magnesium, Day 7 | 0.10 Milliequivalents per liter | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Magnesium, Day 10 | 0.00 Milliequivalents per liter | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Sodium, Day 3 | 0.5 Milliequivalents per liter | Standard Deviation 0.71 |
| Placebo | Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium | Sodium, Day 7 | 0.5 Milliequivalents per liter | Standard Deviation 0.71 |
Primary
Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen
Blood samples for assessment of clinical chemistry parameters of direct bilirubin, total bilirubin, calcium, cholesterol, creatinine, glucose, HDL cholesterol direct, LDL cholesterol calculation, triglycerides,Urea/BUN was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 3, 7, 10
Population: Safety population. Only those participants available at the indicated time points were analyzed. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Glucose, Day 3 | 16.1 Milligrams per deciliter | Standard Deviation 28.35 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Calcium, Day 10 | -0.09 Milligrams per deciliter | Standard Deviation 0.254 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Glucose, Day 7 | -16.5 Milligrams per deciliter | Standard Deviation 45.62 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Direct bilirubin, Day 7 | -0.10 Milligrams per deciliter | Standard Deviation 0.126 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Glucose, Day 10 | 0.1 Milligrams per deciliter | Standard Deviation 5.81 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Cholesterol, Day 3 | 5.7 Milligrams per deciliter | Standard Deviation 8.9 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | HDL cholesterol, direct, Day 3 | -0.6 Milligrams per deciliter | Standard Deviation 2.44 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Total bilirubin, Day 10 | 0.00 Milligrams per deciliter | Standard Deviation 0.216 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | HDL cholesterol, direct, Day 7 | -0.2 Milligrams per deciliter | Standard Deviation 9.62 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Cholesterol, Day 7 | 16.2 Milligrams per deciliter | Standard Deviation 32.6 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | HDL cholesterol, direct, Day 10 | 1.9 Milligrams per deciliter | Standard Deviation 4.56 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Total bilirubin, Day 3 | -0.06 Milligrams per deciliter | Standard Deviation 0.207 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | LDL cholesterol calculation, Day 3 | 6.7 Milligrams per deciliter | Standard Deviation 9.21 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Cholesterol, Day 10 | 4.0 Milligrams per deciliter | Standard Deviation 13.17 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | LDL cholesterol calculation, Day 7 | -0.2 Milligrams per deciliter | Standard Deviation 9.93 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Calcium, Day 3 | 0.13 Milligrams per deciliter | Standard Deviation 0.198 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | LDL cholesterol calculation, Day 10 | 1.6 Milligrams per deciliter | Standard Deviation 10.42 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Creatinine, Day 3 | 0.03 Milligrams per deciliter | Standard Deviation 0.049 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Triglycerides, Day 3 | -1.9 Milligrams per deciliter | Standard Deviation 49.69 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Direct bilirubin, Day 10 | -0.06 Milligrams per deciliter | Standard Deviation 0.053 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Triglycerides, Day 7 | 258.3 Milligrams per deciliter | Standard Deviation 636.46 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Creatinine, Day 7 | 0.05 Milligrams per deciliter | Standard Deviation 0.105 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Triglycerides, Day 10 | 3.6 Milligrams per deciliter | Standard Deviation 39.59 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Calcium, Day 7 | 0.17 Milligrams per deciliter | Standard Deviation 0.207 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Urea/BUN, Day 3 | 1.4 Milligrams per deciliter | Standard Deviation 2.15 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Creatinine, Day 10 | 0.03 Milligrams per deciliter | Standard Deviation 0.076 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Urea/BUN, Day 7 | 1.3 Milligrams per deciliter | Standard Deviation 3.27 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Total bilirubin, Day 7 | -0.03 Milligrams per deciliter | Standard Deviation 0.186 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Urea/BUN, Day 10 | 0.7 Milligrams per deciliter | Standard Deviation 2.81 |
| GSK1265744 5 mg | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Direct bilirubin, Day 3 | -0.04 Milligrams per deciliter | Standard Deviation 0.113 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Urea/BUN, Day 10 | -2.0 Milligrams per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Direct bilirubin, Day 3 | -0.05 Milligrams per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Direct bilirubin, Day 7 | -0.05 Milligrams per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Direct bilirubin, Day 10 | 0.00 Milligrams per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Total bilirubin, Day 3 | -0.25 Milligrams per deciliter | Standard Deviation 0.354 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Total bilirubin, Day 7 | -0.40 Milligrams per deciliter | Standard Deviation 0.566 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Total bilirubin, Day 10 | -0.10 Milligrams per deciliter | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Calcium, Day 3 | 0.00 Milligrams per deciliter | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Calcium, Day 7 | 0.05 Milligrams per deciliter | Standard Deviation 0.495 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Calcium, Day 10 | 0.20 Milligrams per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Cholesterol, Day 3 | -7.5 Milligrams per deciliter | Standard Deviation 9.19 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Cholesterol, Day 7 | 0.0 Milligrams per deciliter | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Cholesterol, Day 10 | 1.0 Milligrams per deciliter | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Creatinine, Day 3 | 0.05 Milligrams per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Creatinine, Day 7 | 0.05 Milligrams per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Creatinine, Day 10 | 0.05 Milligrams per deciliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Glucose, Day 3 | 2.0 Milligrams per deciliter | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Glucose, Day 7 | 4.5 Milligrams per deciliter | Standard Deviation 3.54 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Glucose, Day 10 | -4.0 Milligrams per deciliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | HDL cholesterol, direct, Day 3 | -1.5 Milligrams per deciliter | Standard Deviation 2.12 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | HDL cholesterol, direct, Day 7 | 0.5 Milligrams per deciliter | Standard Deviation 0.71 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | HDL cholesterol, direct, Day 10 | -2.0 Milligrams per deciliter | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | LDL cholesterol calculation, Day 3 | -7.0 Milligrams per deciliter | Standard Deviation 12.73 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | LDL cholesterol calculation, Day 7 | 3.5 Milligrams per deciliter | Standard Deviation 6.36 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | LDL cholesterol calculation, Day 10 | -2.5 Milligrams per deciliter | Standard Deviation 16.26 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Triglycerides, Day 3 | 5.0 Milligrams per deciliter | Standard Deviation 4.24 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Triglycerides, Day 7 | -20.5 Milligrams per deciliter | Standard Deviation 21.92 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Triglycerides, Day 10 | 28.5 Milligrams per deciliter | Standard Deviation 72.83 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Urea/BUN, Day 3 | -1.0 Milligrams per deciliter | Standard Deviation 5.66 |
| Placebo | Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen | Urea/BUN, Day 7 | -2.5 Milligrams per deciliter | Standard Deviation 4.95 |
Primary
Change From Baseline in Electrocardiogram (ECG) Parameters
All ECGs were obtained after a minimum 10 minute rest in a semi-supine position. The 12-lead ECGs were obtained at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10 using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and Bazett's correction (QTcB) and Fridericia correction (QTcF) intervals. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10
Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | PR, Day 7, Pre dose | -0.9 Milliseconds (msec) | Standard Deviation 4.67 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QT, Day 10, Pre dose | -3.3 Milliseconds (msec) | Standard Deviation 14.14 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QRS, Day 7, Pre dose | -0.1 Milliseconds (msec) | Standard Deviation 4.26 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QT, Day 10, 2 Hours | 19.0 Milliseconds (msec) | Standard Deviation 22.15 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | PR, Day 10, 2 Hours | 4.3 Milliseconds (msec) | Standard Deviation 10.09 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcB, Day 1, 2 Hours | 0.2 Milliseconds (msec) | Standard Deviation 13.5 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QRS, Day 10, Pre dose | 1.0 Milliseconds (msec) | Standard Deviation 5.07 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcB, Day 4, Pre dose | 2.0 Milliseconds (msec) | Standard Deviation 16.15 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | PR, Day 4, Pre dose | 4.0 Milliseconds (msec) | Standard Deviation 5.42 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcB, Day 7, Pre dose | -0.0 Milliseconds (msec) | Standard Deviation 16.95 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QRS, Day 10, 2 Hours | -0.7 Milliseconds (msec) | Standard Deviation 8.99 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcB, Day 10, Pre dose | 1.4 Milliseconds (msec) | Standard Deviation 16.59 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QRS, Day 1, 2 Hours | -0.7 Milliseconds (msec) | Standard Deviation 3.68 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcB, Day 10, 2 Hours | -2.4 Milliseconds (msec) | Standard Deviation 12.35 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QT, Day 1, 2 Hours | 18.1 Milliseconds (msec) | Standard Deviation 8.07 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcF, Day 1, 2 Hours | 6.4 Milliseconds (msec) | Standard Deviation 11.45 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | PR, Day 10, Pre dose | -1.7 Milliseconds (msec) | Standard Deviation 3.04 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcF, Day 4, Pre dose | -2.4 Milliseconds (msec) | Standard Deviation 14.27 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QT, Day 4, Pre dose | -10.7 Milliseconds (msec) | Standard Deviation 20.93 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcF, Day 7, Pre dose | -4.7 Milliseconds (msec) | Standard Deviation 13.05 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QRS, Day 4, Pre dose | 0.7 Milliseconds (msec) | Standard Deviation 2.36 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcF, Day 10, Pre dose | -0.2 Milliseconds (msec) | Standard Deviation 13.17 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QT, Day 7, Pre dose | -13.6 Milliseconds (msec) | Standard Deviation 13.13 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcF, Day 10, 2 Hours | 4.9 Milliseconds (msec) | Standard Deviation 13.62 |
| GSK1265744 5 mg | Change From Baseline in Electrocardiogram (ECG) Parameters | PR, Day 1, 2 Hours | 0.0 Milliseconds (msec) | Standard Deviation 1.83 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcF, Day 10, 2 Hours | -3.4 Milliseconds (msec) | Standard Deviation 7.99 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | PR, Day 1, 2 Hours | 1.0 Milliseconds (msec) | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | PR, Day 4, Pre dose | 5.0 Milliseconds (msec) | Standard Deviation 11.31 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | PR, Day 7, Pre dose | 0.0 Milliseconds (msec) | Standard Deviation 12.73 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | PR, Day 10, Pre dose | 0.0 Milliseconds (msec) | Standard Deviation 9.9 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | PR, Day 10, 2 Hours | 4.0 Milliseconds (msec) | Standard Deviation 12.73 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QRS, Day 1, 2 Hours | 1.5 Milliseconds (msec) | Standard Deviation 0.71 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QRS, Day 4, Pre dose | -3.5 Milliseconds (msec) | Standard Deviation 12.02 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QRS, Day 7, Pre dose | 3.5 Milliseconds (msec) | Standard Deviation 2.12 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QRS, Day 10, Pre dose | 0.5 Milliseconds (msec) | Standard Deviation 3.54 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QRS, Day 10, 2 Hours | 5.5 Milliseconds (msec) | Standard Deviation 4.95 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QT, Day 1, 2 Hours | 27.0 Milliseconds (msec) | Standard Deviation 24.04 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QT, Day 4, Pre dose | 5.0 Milliseconds (msec) | Standard Deviation 7.07 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QT, Day 7, Pre dose | 11.0 Milliseconds (msec) | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QT, Day 10, Pre dose | -11.0 Milliseconds (msec) | Standard Deviation 24.04 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QT, Day 10, 2 Hours | 25.0 Milliseconds (msec) | Standard Deviation 24.04 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcB, Day 1, 2 Hours | 6.0 Milliseconds (msec) | Standard Deviation 4.09 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcB, Day 4, Pre dose | -17.9 Milliseconds (msec) | Standard Deviation 2.2 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcB, Day 7, Pre dose | -9.0 Milliseconds (msec) | Standard Deviation 25.73 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcB, Day 10, Pre dose | -15.6 Milliseconds (msec) | Standard Deviation 10.35 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcB, Day 10, 2 Hours | -18.1 Milliseconds (msec) | Standard Deviation 0.42 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcF, Day 1, 2 Hours | 13.3 Milliseconds (msec) | Standard Deviation 11.06 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcF, Day 4, Pre dose | -10.0 Milliseconds (msec) | Standard Deviation 4.05 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcF, Day 7, Pre dose | -2.0 Milliseconds (msec) | Standard Deviation 16.3 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters | QTcF, Day 10, Pre dose | -13.9 Milliseconds (msec) | Standard Deviation 15.19 |
Primary
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count
Blood samples for assessment of hematology parameters of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC- absolute neutrophil count) and white blood cell count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 3, 7, 10
Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Basophils, Day 3 | 0.017 Thousand cells per microliter | Standard Deviation 0.0287 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Basophils, Day 7 | 0.007 Thousand cells per microliter | Standard Deviation 0.0125 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Basophils, Day 10 | 0.009 Thousand cells per microliter | Standard Deviation 0.0146 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Eosinophils, Day 3 | -0.024 Thousand cells per microliter | Standard Deviation 0.0408 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Eosinophils, Day 7 | -0.039 Thousand cells per microliter | Standard Deviation 0.0498 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Eosinophils, Day 10 | -0.009 Thousand cells per microliter | Standard Deviation 0.0628 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Lymphocytes, Day 3 | 0.197 Thousand cells per microliter | Standard Deviation 0.287 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Lymphocytes, Day 7 | 0.190 Thousand cells per microliter | Standard Deviation 0.2514 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Lymphocytes, Day 10 | 0.229 Thousand cells per microliter | Standard Deviation 0.2738 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Monocytes, Day 3 | -0.030 Thousand cells per microliter | Standard Deviation 0.0876 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Monocytes, Day 7 | -0.039 Thousand cells per microliter | Standard Deviation 0.1126 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Monocytes, Day 10 | 0.056 Thousand cells per microliter | Standard Deviation 0.0774 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Total Neutrophils, Day 3 | 0.181 Thousand cells per microliter | Standard Deviation 0.6097 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Total Neutrophils, Day 7 | -0.003 Thousand cells per microliter | Standard Deviation 0.6304 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Total Neutrophils, Day 10 | 0.831 Thousand cells per microliter | Standard Deviation 1.6043 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | White blood cell count, Day 3 | 0.34 Thousand cells per microliter | Standard Deviation 0.282 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | White blood cell count, Day 7 | 0.11 Thousand cells per microliter | Standard Deviation 0.782 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | White blood cell count, Day 10 | 1.11 Thousand cells per microliter | Standard Deviation 1.508 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Total Neutrophils, Day 7 | -0.155 Thousand cells per microliter | Standard Deviation 0.2192 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Basophils, Day 3 | 0.005 Thousand cells per microliter | Standard Deviation 0.0071 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Monocytes, Day 3 | 0.170 Thousand cells per microliter | Standard Deviation 0.2121 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Basophils, Day 7 | 0.015 Thousand cells per microliter | Standard Deviation 0.0071 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | White blood cell count, Day 10 | -0.35 Thousand cells per microliter | Standard Deviation 1.626 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Basophils, Day 10 | 0.020 Thousand cells per microliter | Standard Deviation 0 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Monocytes, Day 7 | 0.035 Thousand cells per microliter | Standard Deviation 0.1626 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Eosinophils, Day 3 | 0.250 Thousand cells per microliter | Standard Deviation 0.4101 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Total Neutrophils, Day 10 | 0.405 Thousand cells per microliter | Standard Deviation 1.1384 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Eosinophils, Day 7 | 0.325 Thousand cells per microliter | Standard Deviation 0.5869 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Monocytes, Day 10 | -0.005 Thousand cells per microliter | Standard Deviation 0.2192 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Eosinophils, Day 10 | -0.055 Thousand cells per microliter | Standard Deviation 0.1485 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | White blood cell count, Day 7 | -0.30 Thousand cells per microliter | Standard Deviation 1.131 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Lymphocytes, Day 3 | -0.500 Thousand cells per microliter | Standard Deviation 0.3111 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Total Neutrophils, Day 3 | -0.080 Thousand cells per microliter | Standard Deviation 0.1273 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Lymphocytes, Day 7 | -0.525 Thousand cells per microliter | Standard Deviation 0.1485 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | White blood cell count, Day 3 | -0.15 Thousand cells per microliter | Standard Deviation 1.061 |
| Placebo | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count | Lymphocytes, Day 10 | -0.720 Thousand cells per microliter | Standard Deviation 0.5515 |
Primary
Change From Baseline in Hematology Parameters: Hemoglobin
Blood samples for assessment of hematology parameter of hemoglobin was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 3, 7, 10
Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Hemoglobin | Day 3 | 0.13 Grams per deciliter | Standard Deviation 0.637 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Hemoglobin | Day 7 | 0.06 Grams per deciliter | Standard Deviation 0.519 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Hemoglobin | Day 10 | -0.17 Grams per deciliter | Standard Deviation 0.446 |
| Placebo | Change From Baseline in Hematology Parameters: Hemoglobin | Day 3 | -0.30 Grams per deciliter | Standard Deviation 0.424 |
| Placebo | Change From Baseline in Hematology Parameters: Hemoglobin | Day 7 | 0.00 Grams per deciliter | Standard Deviation 0.424 |
| Placebo | Change From Baseline in Hematology Parameters: Hemoglobin | Day 10 | -0.15 Grams per deciliter | Standard Deviation 0.354 |
Primary
Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin
Blood samples for assessment of hematology parameter of mean corpuscle hemoglobin was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 3, 7, 10
Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin | Day 3 | -0.03 Picogram | Standard Deviation 0.198 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin | Day 7 | 0.37 Picogram | Standard Deviation 0.411 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin | Day 10 | 0.00 Picogram | Standard Deviation 0.306 |
| Placebo | Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin | Day 3 | 0.25 Picogram | Standard Deviation 0.495 |
| Placebo | Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin | Day 7 | 0.30 Picogram | Standard Deviation 0.141 |
| Placebo | Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin | Day 10 | 0.40 Picogram | Standard Deviation 0.424 |
Primary
Change From Baseline in Hematology Parameters: Mean Corpuscle Volume
Blood samples for assessment of hematology parameter of mean corpuscle volume was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 3, 7, 10
Population: Safety Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Mean Corpuscle Volume | Day 3 | 1.0 Femtoliter | Standard Deviation 1.15 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Mean Corpuscle Volume | Day 7 | 1.0 Femtoliter | Standard Deviation 1.63 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Mean Corpuscle Volume | Day 10 | 1.7 Femtoliter | Standard Deviation 1.11 |
| Placebo | Change From Baseline in Hematology Parameters: Mean Corpuscle Volume | Day 3 | 0.5 Femtoliter | Standard Deviation 0.71 |
| Placebo | Change From Baseline in Hematology Parameters: Mean Corpuscle Volume | Day 7 | -0.5 Femtoliter | Standard Deviation 0.71 |
| Placebo | Change From Baseline in Hematology Parameters: Mean Corpuscle Volume | Day 10 | 0.0 Femtoliter | Standard Deviation 1.41 |
Primary
Change From Baseline in Hematology Parameters: Platelet Count
Blood samples for assessment of hematology parameter of platelet count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 3, 7, 10
Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Platelet Count | Day 3 | 10428.6 Cells per cubic millimeter | Standard Deviation 8847.92 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Platelet Count | Day 7 | 15142.9 Cells per cubic millimeter | Standard Deviation 29299.76 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Platelet Count | Day 10 | 8000.0 Cells per cubic millimeter | Standard Deviation 23860.71 |
| Placebo | Change From Baseline in Hematology Parameters: Platelet Count | Day 3 | 5000.0 Cells per cubic millimeter | Standard Deviation 21213.2 |
| Placebo | Change From Baseline in Hematology Parameters: Platelet Count | Day 7 | 2500.0 Cells per cubic millimeter | Standard Deviation 2121.32 |
| Placebo | Change From Baseline in Hematology Parameters: Platelet Count | Day 10 | 9500.0 Cells per cubic millimeter | Standard Deviation 37476.66 |
Primary
Change From Baseline in Hematology Parameters: Red Blood Cell Count
Blood samples for assessment of hematology parameter of red blood cell count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 3, 7, 10
Population: Safety Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Red Blood Cell Count | Day 3 | 0.03 Million cells per microliter | Standard Deviation 0.221 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Red Blood Cell Count | Day 7 | -0.06 Million cells per microliter | Standard Deviation 0.151 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Red Blood Cell Count | Day 10 | -0.09 Million cells per microliter | Standard Deviation 0.135 |
| Placebo | Change From Baseline in Hematology Parameters: Red Blood Cell Count | Day 3 | -0.15 Million cells per microliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Hematology Parameters: Red Blood Cell Count | Day 7 | -0.05 Million cells per microliter | Standard Deviation 0.071 |
| Placebo | Change From Baseline in Hematology Parameters: Red Blood Cell Count | Day 10 | -0.10 Million cells per microliter | Standard Deviation 0.141 |
Primary
Change From Baseline in Hematology Parameters: Reticulocytes
Blood samples for assessment of hematology parameter of reticulocytes was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 3, 7, 10
Population: Safety Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Reticulocytes | Day 3 | 5.51 Giga cells per liter | Standard Deviation 9.971 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Reticulocytes | Day 7 | 13.79 Giga cells per liter | Standard Deviation 27.361 |
| GSK1265744 5 mg | Change From Baseline in Hematology Parameters: Reticulocytes | Day 10 | 13.79 Giga cells per liter | Standard Deviation 16.419 |
| Placebo | Change From Baseline in Hematology Parameters: Reticulocytes | Day 3 | 9.45 Giga cells per liter | Standard Deviation 1.768 |
| Placebo | Change From Baseline in Hematology Parameters: Reticulocytes | Day 7 | -6.50 Giga cells per liter | Standard Deviation 0.849 |
| Placebo | Change From Baseline in Hematology Parameters: Reticulocytes | Day 10 | 21.30 Giga cells per liter | Standard Deviation 35.497 |
Primary
Change From Baseline in Plasma Human Immunodeficiency Virus (HIV-1) Ribonucleic Acid (RNA) to Day 11
Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a lower limit of detection (LLOD) of 50 copies/milliliter (mL) (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 11
Population: Intent-to-treat (ITT) population comprised of all participants who met study criteria and randomized into study with documented evidence of having received at least 1 dose of randomized treatment and at least 1 post-baseline HIV-1 RNA measurement. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Plasma Human Immunodeficiency Virus (HIV-1) Ribonucleic Acid (RNA) to Day 11 | -2.169 log10 copies/mL | Standard Deviation 0.2405 |
| Placebo | Change From Baseline in Plasma Human Immunodeficiency Virus (HIV-1) Ribonucleic Acid (RNA) to Day 11 | -0.092 log10 copies/mL | Standard Deviation 0.1499 |
p-value: <0.00195% CI: [-2.547, -1.632]ANCOVA
Primary
Change From Baseline in Vital Sign: Heart Rate
Heart rate was measured at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10
Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Heart Rate | Day 4, Pre dose | 5.3 Beats per minute | Standard Deviation 6.24 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Heart Rate | Day 10, Pre dose | 0.0 Beats per minute | Standard Deviation 6.74 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Heart Rate | Day 7, Pre dose | 6.3 Beats per minute | Standard Deviation 5.71 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Heart Rate | Day 10, 2 Hours | -7.6 Beats per minute | Standard Deviation 5.12 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Heart Rate | Day 1, 2 Hours | -7.0 Beats per minute | Standard Deviation 2.1 |
| Placebo | Change From Baseline in Vital Sign: Heart Rate | Day 10, 2 Hours | -10.8 Beats per minute | Standard Deviation 3.18 |
| Placebo | Change From Baseline in Vital Sign: Heart Rate | Day 1, 2 Hours | -5.8 Beats per minute | Standard Deviation 4.6 |
| Placebo | Change From Baseline in Vital Sign: Heart Rate | Day 4, Pre dose | -5.8 Beats per minute | Standard Deviation 1.06 |
| Placebo | Change From Baseline in Vital Sign: Heart Rate | Day 7, Pre dose | -1.8 Beats per minute | Standard Deviation 1.77 |
| Placebo | Change From Baseline in Vital Sign: Heart Rate | Day 10, Pre dose | 5.8 Beats per minute | Standard Deviation 4.6 |
Primary
Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure
Systolic and diastolic blood pressure was measured at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10
Population: Safety population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Systolic blood pressure, Day 1, 2 Hours | 1.2 Millimeters of mercury (mmHg) | Standard Deviation 8.59 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Systolic blood pressure, Day 4, Pre dose | 1.8 Millimeters of mercury (mmHg) | Standard Deviation 9.16 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Systolic blood pressure, Day 7, Pre dose | -2.5 Millimeters of mercury (mmHg) | Standard Deviation 11.22 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Systolic blood pressure, Day 10, Pre dose | 0.6 Millimeters of mercury (mmHg) | Standard Deviation 19.19 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Systolic blood pressure, Day 10, 2 Hours | -0.2 Millimeters of mercury (mmHg) | Standard Deviation 10.59 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Diastolic blood pressure, Day 1, 2 Hours | -5.7 Millimeters of mercury (mmHg) | Standard Deviation 5.76 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Diastolic blood pressure, Day 4, Pre dose | -2.4 Millimeters of mercury (mmHg) | Standard Deviation 8.91 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Diastolic blood pressure, Day 7, Pre dose | -1.6 Millimeters of mercury (mmHg) | Standard Deviation 9.28 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Diastolic blood pressure, Day 10, Pre dose | -5.4 Millimeters of mercury (mmHg) | Standard Deviation 13.85 |
| GSK1265744 5 mg | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Diastolic blood pressure, Day 10, 2 Hours | -2.4 Millimeters of mercury (mmHg) | Standard Deviation 6.82 |
| Placebo | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Diastolic blood pressure, Day 7, Pre dose | -5.0 Millimeters of mercury (mmHg) | Standard Deviation 15.56 |
| Placebo | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Systolic blood pressure, Day 1, 2 Hours | 5.8 Millimeters of mercury (mmHg) | Standard Deviation 0.35 |
| Placebo | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Diastolic blood pressure, Day 1, 2 Hours | -0.5 Millimeters of mercury (mmHg) | Standard Deviation 2.12 |
| Placebo | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Systolic blood pressure, Day 4, Pre dose | 5.8 Millimeters of mercury (mmHg) | Standard Deviation 3.18 |
| Placebo | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Diastolic blood pressure, Day 10, 2 Hours | 6.5 Millimeters of mercury (mmHg) | Standard Deviation 9.19 |
| Placebo | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Systolic blood pressure, Day 7, Pre dose | -4.3 Millimeters of mercury (mmHg) | Standard Deviation 8.84 |
| Placebo | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Diastolic blood pressure, Day 4, Pre dose | -2.5 Millimeters of mercury (mmHg) | Standard Deviation 10.61 |
| Placebo | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Systolic blood pressure, Day 10, Pre dose | 19.8 Millimeters of mercury (mmHg) | Standard Deviation 14.5 |
| Placebo | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Diastolic blood pressure, Day 10, Pre dose | 8.5 Millimeters of mercury (mmHg) | Standard Deviation 14.85 |
| Placebo | Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure | Systolic blood pressure, Day 10, 2 Hours | 13.3 Millimeters of mercury (mmHg) | Standard Deviation 4.6 |
Primary
GSK1265744 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments(AUC[0-24])
Blood samples for PK analysis of AUC(0-24) of GSK1265744 was collected on Day 1 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time frame: Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)
Population: PK Summary Population included participants with evaluable PK profile of GSK1265744 on Day 10. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK1265744 5 mg | GSK1265744 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments(AUC[0-24]) | 7.53 Hour*microgram per milliliter (hr*µg/mL) | Geometric Coefficient of Variation 23 |
Primary
GSK1265744 PK Parameters Following Dose Administration on Day 10: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau])
Blood samples for PK analysis of C24 of GSK1265744 was collected on Day 10 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time frame: Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)
Population: PK summary population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK1265744 5 mg | GSK1265744 PK Parameters Following Dose Administration on Day 10: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) | 17.74 hr*µg/mL | Geometric Coefficient of Variation 31 |
Primary
GSK1265744 PK Parameters Following Dose Administration on Day 10: Predose Concentration (C0), Concentration at End of Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin)
Blood samples for PK analysis of C0, Ctau and Cmin of GSK1265744 was collected on Day 10 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.
Time frame: Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)
Population: PK Summary Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | GSK1265744 PK Parameters Following Dose Administration on Day 10: Predose Concentration (C0), Concentration at End of Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin) | C0 | 0.54 µg/mL | Geometric Coefficient of Variation 36 |
| GSK1265744 5 mg | GSK1265744 PK Parameters Following Dose Administration on Day 10: Predose Concentration (C0), Concentration at End of Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin) | Ctau | 0.57 µg/mL | Geometric Coefficient of Variation 33 |
| GSK1265744 5 mg | GSK1265744 PK Parameters Following Dose Administration on Day 10: Predose Concentration (C0), Concentration at End of Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin) | Cmin | 0.53 µg/mL | Geometric Coefficient of Variation 35 |
Primary
GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Maximum Observed Concentration (Cmax)
Blood samples for PK analysis of Cmax of GSK1265744 was collected at pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10. Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.
Time frame: Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10
Population: PK Summary Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Maximum Observed Concentration (Cmax) | Day 1 | 0.52 µg/mL | Geometric Coefficient of Variation 20 |
| GSK1265744 5 mg | GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Maximum Observed Concentration (Cmax) | Day 10 | 1.02 µg/mL | Geometric Coefficient of Variation 25 |
Primary
GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Terminal Half-life (t1/2) and Absorption Lag Time (Tlag)
PK sampling was planned to be collected up to 24 hours only on Day 1 and Day 10. The data for this outcome measure was however not collected.
Time frame: Day 1 and Day 10
Population: PK Summary Population. Data for this outcome measure was not collected. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
Primary
GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Time to Cmax (Tmax)
Blood samples for PK analysis of tmax of GSK1265744 was collected at pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10. Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.
Time frame: Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10
Population: PK Summary Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GSK1265744 5 mg | GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Time to Cmax (Tmax) | Day 1 | 2.00 Hour |
| GSK1265744 5 mg | GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Time to Cmax (Tmax) | Day 10 | 2.00 Hour |
Primary
GSK1265744 PK Parameters Following Dose Administration on Day 1: Concentration at 24 Hours Post Dose (C24)
Blood samples for PK analysis of C24 of GSK1265744 was collected on Day 1 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.
Time frame: Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)
Population: PK summary population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK1265744 5 mg | GSK1265744 PK Parameters Following Dose Administration on Day 1: Concentration at 24 Hours Post Dose (C24) | 0.23 Micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 28 |
Primary
GSK1265744 PK Parameters Following Last Repeat Administration on Day 10: Apparent Clearance Following Oral Dosing (CL/F)
Blood samples for PK analysis of CL/F of GSK1265744 was collected on Day 10 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.
Time frame: Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)
Population: PK Summary Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK1265744 5 mg | GSK1265744 PK Parameters Following Last Repeat Administration on Day 10: Apparent Clearance Following Oral Dosing (CL/F) | 0.28 Liter per hour (L/hr) | Geometric Coefficient of Variation 31 |
Primary
Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, medically significant or is associated with liver injury and impaired liver function.
Time frame: Day 1 to Day 11
Population: Safety population was defined as all participants who were randomized into the study with documented evidence of having received at least 1 dose of randomized treatment. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK1265744 5 mg | Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 0 Participants |
| GSK1265744 5 mg | Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| Placebo | Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 2 Participants |
| Placebo | Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| Optimized Therapy | Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 3 Participants |
| Optimized Therapy | Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
Primary
Number of Participants With Urinalysis Data
Samples for urinalysis assessment was collected on Day 1, Day 3 and Day 10. Urinalysis parameters included urine bilirubin, urine occult blood, urine glucose, urine ketones, urine nitrite, urine pH, urine protein, urine specific gravity and urine leukocyte esterase test for detecting white blood cell.
Time frame: Day 1 to Day 10
Population: Safety Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Protein, Trace | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.021 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.016 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Bilirubin, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.017 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.025 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.018 | 0 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine pH, 6.5 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.021 | 2 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.03 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.022 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Nitrite, Negative | 6 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.027 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, ULET for white blood cell, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.03 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Protein, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, ULET for white blood cell, 2+ | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Bilirubin, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, ULET for white blood cell, Negative | 6 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Glucose, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Bilirubin, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Occult Blood, Negative | 6 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Occult Blood, 2+ | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.006 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Occult Blood, Negative | 6 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Occult Blood, 1+ | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Glucose, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Nitrite, Positive | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Ketones, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Glucose, 3+ | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Nitrite, Negative | 6 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.014 | 0 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Nitrite, Positive | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Glucose, Negative | 6 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine pH, 5.5 | 0 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Occult Blood, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine pH, 6 | 4 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Ketones, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine pH, 6.5 | 3 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.015 | 0 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Protein, Negative | 5 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Nitrite, Negative | 6 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Protein, Trace | 2 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine pH, 5.5 | 2 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.009 | 0 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Nitrite, Positive | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.016 | 0 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.017 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.02 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine pH, 5.5 | 4 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.021 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Ketones, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.023 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine pH, 6 | 2 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.025 | 2 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.019 | 2 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.027 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine Protein, Negative | 6 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.03 | 1 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 1, Urine pH, 6 | 4 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 10, ULET for white blood cell, Negative | 7 Participants |
| GSK1265744 5 mg | Number of Participants With Urinalysis Data | Day 3, Urine pH, 6.5 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, ULET for white blood cell, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine pH, 6 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Bilirubin, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Occult Blood, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Glucose, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Ketones, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Nitrite, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Nitrite, Positive | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine pH, 5.5 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine pH, 6 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine pH, 6.5 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Protein, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.006 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.014 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.015 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.017 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.019 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.021 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.025 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, Urine Specific Gravity, 1.03 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 1, ULET for white blood cell, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Bilirubin, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Occult Blood, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Occult Blood, 1+ | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Glucose, 3+ | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Glucose, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Ketones, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Nitrite, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Nitrite, Positive | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine pH, 5.5 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine pH, 6.5 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Protein, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Protein, Trace | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.016 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.017 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.018 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.021 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.022 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.027 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, Urine Specific Gravity, 1.03 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, ULET for white blood cell, 2+ | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 3, ULET for white blood cell, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Bilirubin, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Occult Blood, 2+ | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Occult Blood, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Glucose, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Ketones, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Nitrite, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Nitrite, Positive | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine pH, 5.5 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine pH, 6 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine pH, 6.5 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Protein, Negative | 2 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Protein, Trace | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.009 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.016 | 1 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.02 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.021 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.023 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.025 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.027 | 0 Participants |
| Placebo | Number of Participants With Urinalysis Data | Day 10, Urine Specific Gravity, 1.03 | 0 Participants |
Secondary
Accumulation Ratios for AUC, Cmax, and Ctau
The accumulation ratio was calculated as the ratio of AUC(0-τ), Cmax, and Ctau on Day 10 to AUC(0-24), Cmax, and C24 on Day 1 for each participant. The ratio of geometric least square means of each parameter on Day 10 to Day 1 was presented along with 90% confidence interval.
Time frame: Days 1 and 10
Population: PK/ Pharmacodynamic (PD) Summary Population included participants who met the criteria for both ITT Population and PK Summary Population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|---|
| GSK1265744 5 mg | Accumulation Ratios for AUC, Cmax, and Ctau | Accumulation Ratio AUC | 2.355 Ratio |
| GSK1265744 5 mg | Accumulation Ratios for AUC, Cmax, and Ctau | Accumulation Ratio Cmax | 1.961 Ratio |
| GSK1265744 5 mg | Accumulation Ratios for AUC, Cmax, and Ctau | Accumulation Ratio Ctau | 2.483 Ratio |
Secondary
Change From Baseline in CD4+ Cell Count to Day 11
Whole venous blood samples was obtained from each participant for the analysis of lymphocyte subsets by flow cytometry on Day 1 and Day 11. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 11
Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in CD4+ Cell Count to Day 11 | 71.0 Cells per cubic millimeter | Standard Deviation 56.62 |
| Placebo | Change From Baseline in CD4+ Cell Count to Day 11 | -84.0 Cells per cubic millimeter | Standard Deviation 145.66 |
Secondary
Change From Baseline in Plasma HIV-1 RNA
Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA were collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Baseline was defined at Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1 pre-dose) and Day 1 (post dose), 2, 3, 4, 7, 8, 9, 10
Population: ITT population. Only those participants available at the indicated time points were analyzed. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Plasma HIV-1 RNA | Day 1 | 0.000 Log10 copies/mL | Standard Deviation 0 |
| GSK1265744 5 mg | Change From Baseline in Plasma HIV-1 RNA | Day 2 | -0.126 Log10 copies/mL | Standard Deviation 0.2255 |
| GSK1265744 5 mg | Change From Baseline in Plasma HIV-1 RNA | Day 3 | -0.618 Log10 copies/mL | Standard Deviation 0.1341 |
| GSK1265744 5 mg | Change From Baseline in Plasma HIV-1 RNA | Day 4 | -0.830 Log10 copies/mL | Standard Deviation 0.2424 |
| GSK1265744 5 mg | Change From Baseline in Plasma HIV-1 RNA | Day 7 | -1.577 Log10 copies/mL | Standard Deviation 0.5498 |
| GSK1265744 5 mg | Change From Baseline in Plasma HIV-1 RNA | Day 8 | -1.935 Log10 copies/mL | Standard Deviation 0.4717 |
| GSK1265744 5 mg | Change From Baseline in Plasma HIV-1 RNA | Day 9 | -2.013 Log10 copies/mL | Standard Deviation 0.4192 |
| GSK1265744 5 mg | Change From Baseline in Plasma HIV-1 RNA | Day 10 | -2.160 Log10 copies/mL | Standard Deviation 0.281 |
| Placebo | Change From Baseline in Plasma HIV-1 RNA | Day 10 | -0.158 Log10 copies/mL | Standard Deviation 0.193 |
| Placebo | Change From Baseline in Plasma HIV-1 RNA | Day 1 | 0.000 Log10 copies/mL | — |
| Placebo | Change From Baseline in Plasma HIV-1 RNA | Day 7 | -0.168 Log10 copies/mL | Standard Deviation 0.1264 |
| Placebo | Change From Baseline in Plasma HIV-1 RNA | Day 2 | 0.058 Log10 copies/mL | Standard Deviation 0.2303 |
| Placebo | Change From Baseline in Plasma HIV-1 RNA | Day 9 | -0.007 Log10 copies/mL | Standard Deviation 0.196 |
| Placebo | Change From Baseline in Plasma HIV-1 RNA | Day 3 | -0.299 Log10 copies/mL | Standard Deviation 0.2737 |
| Placebo | Change From Baseline in Plasma HIV-1 RNA | Day 8 | -0.146 Log10 copies/mL | Standard Deviation 0.2779 |
| Placebo | Change From Baseline in Plasma HIV-1 RNA | Day 4 | -0.146 Log10 copies/mL | Standard Deviation 0.058 |
Secondary
Change From Baseline in Plasma HIV-1 RNA to Nadir Over 11 Days
Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Nadir was the maximum change from Baseline in plasma HIV-1 RNA. Baseline was defined at Day 1 (pre-dose). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time frame: Baseline (Day 1) and Day 11
Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK1265744 5 mg | Change From Baseline in Plasma HIV-1 RNA to Nadir Over 11 Days | -2.199 log10 copies/mL | Standard Deviation 0.2491 |
| Placebo | Change From Baseline in Plasma HIV-1 RNA to Nadir Over 11 Days | -0.418 log10 copies/mL | Standard Deviation 0.1058 |
p-value: <0.00195% CI: [-2.173, -1.436]ANCOVA
Secondary
Day 10 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality Using Power Model
Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following a repeat dose administration on Day 10 (AUC\[0-tau\]) using the power model. The mean slope and corresponding 90% confidence interval has been presented.
Time frame: Day 10
Population: PK Summary Population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GSK1265744 5 mg | Day 10 AUC(0-tau) at Different Doses for the Assessment of Dose Proportionality Using Power Model | 0.988 hr*µg/mL/mg |
Secondary
Day 10 Cmax, C0 and Ctau at Different Doses for the Assessment of Dose Proportionality Using Power Model
Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following a repeat dose administration on Day 10 (Cmax, Ctau and C0) using the power model. The mean slope and corresponding 90% confidence interval has been presented.
Time frame: Day 10
Population: PK Summary Population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| GSK1265744 5 mg | Day 10 Cmax, C0 and Ctau at Different Doses for the Assessment of Dose Proportionality Using Power Model | Cmax | 1.025 µg/mL/mg |
| GSK1265744 5 mg | Day 10 Cmax, C0 and Ctau at Different Doses for the Assessment of Dose Proportionality Using Power Model | C0 | 0.936 µg/mL/mg |
| GSK1265744 5 mg | Day 10 Cmax, C0 and Ctau at Different Doses for the Assessment of Dose Proportionality Using Power Model | Ctau | 0.980 µg/mL/mg |
Secondary
Day 1 AUC(0-24) at Different Doses for the Assessment of Dose Proportionality Using Power Model
Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following single dose administration on Day 1 (AUC\[0-24\]) using the power model. The mean slope and corresponding 90% confidence interval has been presented.
Time frame: Day 1
Population: PK Summary Population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GSK1265744 5 mg | Day 1 AUC(0-24) at Different Doses for the Assessment of Dose Proportionality Using Power Model | 0.952 hr*µg/mL/mg |
Secondary
Day 1 Cmax and C24 at Different Doses for the Assessment of Dose Proportionality Using Power Model
Data from GSK1265744 30 mg in HIV participants (Study ITZ111451 part C HIV cohort, NCT00659191) was combined with data from this study to access dose proportionality. Dose proportionality of GSK1265744 PK parameters was assessed following single dose administration on Day 1 (Cmax, and C24) using the power model. The mean slope and corresponding 90% confidence interval has been presented.
Time frame: Day 1
Population: PK Summary Population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| GSK1265744 5 mg | Day 1 Cmax and C24 at Different Doses for the Assessment of Dose Proportionality Using Power Model | Cmax | 0.950 μg/mL/mg |
| GSK1265744 5 mg | Day 1 Cmax and C24 at Different Doses for the Assessment of Dose Proportionality Using Power Model | C24 | 0.949 μg/mL/mg |
Secondary
Number of Participants With HIV-1 RNA<400 Copies/mL
Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Only categories with data available at the indicated time points have been presented. Categories with null values for all the arms have not been presented.
Time frame: Up to Day 11
Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK1265744 5 mg | Number of Participants With HIV-1 RNA<400 Copies/mL | Day 8 | 4 Participants |
| GSK1265744 5 mg | Number of Participants With HIV-1 RNA<400 Copies/mL | Day 10 | 5 Participants |
| GSK1265744 5 mg | Number of Participants With HIV-1 RNA<400 Copies/mL | Day 9 | 4 Participants |
| GSK1265744 5 mg | Number of Participants With HIV-1 RNA<400 Copies/mL | Day 11 | 5 Participants |
| GSK1265744 5 mg | Number of Participants With HIV-1 RNA<400 Copies/mL | Day 7 | 2 Participants |
| Placebo | Number of Participants With HIV-1 RNA<400 Copies/mL | Day 11 | 0 Participants |
| Placebo | Number of Participants With HIV-1 RNA<400 Copies/mL | Day 7 | 0 Participants |
| Placebo | Number of Participants With HIV-1 RNA<400 Copies/mL | Day 8 | 0 Participants |
| Placebo | Number of Participants With HIV-1 RNA<400 Copies/mL | Day 9 | 0 Participants |
| Placebo | Number of Participants With HIV-1 RNA<400 Copies/mL | Day 10 | 0 Participants |
Secondary
Number of Participants With HIV-1 RNA<50 Copies/mL
Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Only categories with data available at the indicated time points have been presented. Categories with null values for all the arms have not been presented.
Time frame: Up to Day 11
Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK1265744 5 mg | Number of Participants With HIV-1 RNA<50 Copies/mL | Day 8 | 2 Participants |
| GSK1265744 5 mg | Number of Participants With HIV-1 RNA<50 Copies/mL | Day 9 | 3 Participants |
| GSK1265744 5 mg | Number of Participants With HIV-1 RNA<50 Copies/mL | Day 10 | 2 Participants |
| GSK1265744 5 mg | Number of Participants With HIV-1 RNA<50 Copies/mL | Day 11 | 2 Participants |
| Placebo | Number of Participants With HIV-1 RNA<50 Copies/mL | Day 11 | 0 Participants |
| Placebo | Number of Participants With HIV-1 RNA<50 Copies/mL | Day 8 | 0 Participants |
| Placebo | Number of Participants With HIV-1 RNA<50 Copies/mL | Day 10 | 0 Participants |
| Placebo | Number of Participants With HIV-1 RNA<50 Copies/mL | Day 9 | 0 Participants |
Secondary
Plasma HIV-1 RNA Rate of Decline (Slope) Over 11 Days
Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a LLOD of 50 copies/mL (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Estimated mean rate of decline (i.e., slope of day) with corresponding 90% confidence interval was provided for each treatment.
Time frame: Up to Day 10
Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GSK1265744 5 mg | Plasma HIV-1 RNA Rate of Decline (Slope) Over 11 Days | -0.2313 log10 copies per mL per day |
| Placebo | Plasma HIV-1 RNA Rate of Decline (Slope) Over 11 Days | 0.0013 log10 copies per mL per day |
p-value: <0.0001ANCOVA
Secondary
Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration
Steady state is said to be reached, when the pre-dose concentration slope estimate is close to zero. The data for pre-dose concentration on Day 1 24 hours (Day 2) through Day 10 has been presented.
Time frame: Day 1 24 hours (Day 2), Pre-dose on Days 3, 4, 7, 8, 9 and 10
Population: ITT population. GSK1265744 30 mg arm is from study ITZ111451 that was used only for dose proportionality assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK1265744 5 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration | DAY 1, 24 hours (Day 2) | 0.2363 µg/mL | Standard Deviation 0.06884 |
| GSK1265744 5 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration | DAY 3, Pre-dose | 0.3539 µg/mL | Standard Deviation 0.12999 |
| GSK1265744 5 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration | DAY 4, Pre-dose | 0.4128 µg/mL | Standard Deviation 0.15566 |
| GSK1265744 5 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration | DAY 7, Pre-dose | 0.5239 µg/mL | Standard Deviation 0.11899 |
| GSK1265744 5 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration | DAY 8, Pre-dose | 0.5744 µg/mL | Standard Deviation 0.17622 |
| GSK1265744 5 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration | DAY 9, Pre-dose | 0.5688 µg/mL | Standard Deviation 0.1688 |
| GSK1265744 5 mg | Pre-morning Dose Concentrations (C0) on Day 2 Through 10 to Assess the Achievement of Steady State of GSK1265744 Following Repeat Administration | DAY 10, Pre-dose | 0.5654 µg/mL | Standard Deviation 0.20609 |