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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
9
GSK1265744 30 mg
Placebo to match GSK1265744
GSK1265744 5mg
GSK Investigational Site
Fort Lauderdale, Florida, United States
GSK Investigational Site
Orlando, Florida, United States
GSK Investigational Site
Vero Beach, Florida, United States
GSK Investigational Site
Charlotte, North Carolina, United States
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
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)
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)
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)
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)
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
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
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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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
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
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
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
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
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
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
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
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