Single Dose Escalation Study of GSK2838232 in Healthy Subjects
- Conditions
- Infection, Human Immunodeficiency Virus
- Interventions
- Registration Number
- NCT01802918
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
GSK2838232 is a novel human immune virus (HIV) maturation inhibitor being developed for the treatment of chronic HIV infection. This study is the first administration of GSK2838232 in humans to establish the initial safety, tolerability, and pharmacokinetic profile following single doses of GSK2838232 and to evaluate the effect of food and ritonavir (RTV) on GSK2838232 in healthy subjects. There will be 2 cohorts in this study. In Cohort 1, approximately 8 healthy subjects will be enrolled (6 active and 2 placebo) at each dose visit. There will be four dosing sessions for each subject with subjects randomized to receive placebo in a random sequence. In Cohort 2, approximately 8 healthy subjects will be enrolled (6 active doses and 2 placebo doses at each dose visit). Cohort 2 will have four dosing sessions for each subject with subjects randomized to receive placebo in a random sequence.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Cohort 1 GSK2838232 Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): ABCD, BACD, BCAD, or BCDA. Where A=Placebo, B= GSK2838232 5mg, C=GSK2838232 10mg, and D=GSK2838232 20mg Cohort 1 Placebo Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): ABCD, BACD, BCAD, or BCDA. Where A=Placebo, B= GSK2838232 5mg, C=GSK2838232 10mg, and D=GSK2838232 20mg Cohort 2 GSK2838232 Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): EGHJ, FEHJ, FGIJ, or FGHK. Where E=Placebo, F= GSK2838232 50mg, G= GSK2838232 100mg, H= GSK2838232 50mg + food, I= Placebo + food, J= GSK2838232 10mg + RTV, K= placebo + RTV. Cohort 2 Ritonavir Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): EGHJ, FEHJ, FGIJ, or FGHK. Where E=Placebo, F= GSK2838232 50mg, G= GSK2838232 100mg, H= GSK2838232 50mg + food, I= Placebo + food, J= GSK2838232 10mg + RTV, K= placebo + RTV. Cohort 2 Placebo Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): EGHJ, FEHJ, FGIJ, or FGHK. Where E=Placebo, F= GSK2838232 50mg, G= GSK2838232 100mg, H= GSK2838232 50mg + food, I= Placebo + food, J= GSK2838232 10mg + RTV, K= placebo + RTV.
- Primary Outcome Measures
Name Time Method Number of subjects with AEs as a measure of safety and tolerability in cohort 2. Up to 12 weeks AEs will be collected from the start of Study Treatment and until 5 days post last-dose (at follow up).
Absolute values and changes over time of hematology as a measure of safety and tolerability in cohort 2 Up to 12 weeks Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability in cohort 1. Up to 16 weeks Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability in cohort 2. Up to 12 weeks Absolute values and changes over time of urinalysis as a measure of safety and tolerability in cohort 2 Up to 12 weeks Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability in cohort 2. Up to 12 weeks Number of subjects with adverse events (AEs) as a measure of safety and tolerability in cohort 1 Up to 16 weeks AEs will be collected from the start of Study Treatment and until 5 days post last-dose (at follow up).
Absolute values and changes over time of hematology as a measure of safety and tolerability in cohort 1. Up to 16 weeks Absolute values and changes over time of vital signs as a measure of safety and tolerability in cohort 1 Up to 16 weeks. Vital signs include blood pressure, temperature and heart rate measurement
Real time collection and review of heart rhythm using telemetry as a measure of safety and tolerability in cohort 1. Up to 16 weeks. Composite of pharmacokinetics (PK) parameters following single dose administration of GSK2838232 in cohort 1 PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit. PK parameters include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC \[0-infinity\]), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC \[0-t\]), maximum observed concentration (Cmax), time to maximum observed concentration (Tmax), observed concentration at 24hour post-dose (C24), last observed quantifiable concentration (Ct), lag time before observation of drug concentrations in sampled matrix (tlag), terminal half-life (t1/2), and apparent oral clearance (CL/F).
Absolute values and changes over time of urinalysis as a measure of safety and tolerability in cohort 1. Up to 16 weeks Absolute values and changes over time of vital signs as a measure of safety and tolerability in cohort 2. Up to 12 weeks Vital signs include blood pressure, temperature and heart rate measurement
Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability in cohort 1. Up to 16 weeks. Real time collection and review of heart rhythm using telemetry as a measure of safety and tolerability in cohort 2. Up to 12 weeks Composite of pharmacokinetics parameters following single dose administration of GSK2838232 in cohort 2. PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit. PK parameters include: AUC (0-infinity), AUC (0-t), Cmax, Tmax, C24, Ct, tlag, t1/2 and CL/F.
- Secondary Outcome Measures
Name Time Method Composite of pharmacokinetics parameters following single dose administration of GSK2838232 with and without food in cohort 2. PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit. PK parameters include: AUC (0-infinity), AUC (0-t), Cmax, Tmax, C24 and t1/2. Food will be normal fat meal.
Composite of pharmacokinetics parameters following single dose administration of GSK2838232 with co-administration of ritonavir in cohort 2. PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit. PK parameters include: AUC (0-infinity), AUC (0-t), Cmax, Tmax, C24 and t1/2.
Trial Locations
- Locations (1)
GSK Investigational Site
🇺🇸Baltimore, Maryland, United States