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This is a study in healthy adult subjects to evaluate the bioequivalence of a Combined Formulated Tablet compared with maraviroc and Combivir administered concurrently versus maraviroc + Combivir. 42 subjects will be enrolled in the study such that 40 subjects complete dosing and critical assessments. The total duration of a subject's participation will be approximately 33 to 35 days, including a screening period (Day -21 to Day -1), 2 treatment periods (Days 1-3), at least a 7-day washout between Period 1 and Period 2, and a follow-up visit 7 to 14 days after the last dose of study drug in Period 2. Each dosing period will begin the evening prior to dosing and extend until 48 hours (Day 3) after dosing. Subjects will be randomly assigned to receive 1 of the following 2 treatments in Period 1 then crossover to receive the alternate treatment in Period 2:
In Sequence 1 (N=21) subjects will receive Treatment A followed by a 7 day washout and Treatment B. In Sequence 2 (N=21) subjects will receive Treatment B followed by a 7 day washout and Treatment A. Treatment A consists of 1 tablet of maraviroc 300 mg, lamivudine 150 mg, and zidovudine 300 mg as a combined formulation after an overnight fast. Treatment B consists of 1 tablet of maraviroc 300 mg + 1 tablet of Combivir taken concurrently after an overnight fast. On Day 1 of each treatment period, subjects will receive study drug in the morning after an overnight fast of at least 8 hours. Study drug will be administered with 240 mL of water. Dosing in each treatment period will be separated by a minimum washout period of at least 7 days between doses. All subjects will undergo safety and other assessments. Subjects may be discharged after all study procedures are completed on the morning of Day 3, with instructions to return for the next study period or the follow-up visit, as appropriate. The follow-up visit will occur 7 to 14 days after the last dose of study drug in Period 2. Pharmacokinetic blood samples will be collected during each treatment period for evaluation of maraviroc, lamivudine, and zidovudine before dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, and 48 hours after dosing (total of 16 PK time points per treatment period). Protocol waivers or exemptions are not allowed, with the exception of immediate safety concerns. Therefore, adherence to the study protocol requirements, including those specified in the Time and Events Table, are essential and required for study conduct.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1 | Experimental | Treatment A: 1 tablet of GSK2838510 (maraviroc 300 mg, lamivudine 150 mg, and zidovudine 300 mg as a combined formulation) after an overnight fast Washout Treatment B: 1 tablet of maraviroc 300 mg + 1 tablet of Combivir taken concurrently after an overnight fast. |
|
| Sequence 2 | Experimental | Treatment B: 1 tablet of maraviroc 300 mg + 1 tablet of Combivir taken concurrently after an overnight fast. Washout Treatment A: 1 tablet of GSK2838510 (maraviroc 300 mg, lamivudine 150 mg, and zidovudine 300 mg as a combined formulation) after an overnight fast |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Maraviroc | Drug | 300 mg |
| |
| Combivir |
| Measure | Description | Time Frame |
|---|---|---|
| Safety parameters: AEs, vital signs, ECG, body temperature and laboratory assessments, including haematology, clinical biochemistry and cardiac troponin | To assess the safety and tolerability of single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler | Approximately 5 weeks from first dose to the follow-up visit |
| Assessment of oropharyngeal sensation perturbation via a 4 point scale | To assess the changes in oropharyngeal sensation caused by single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler | Approximately 5 weeks from first dose to the follow-up visit |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma concentrations of GSK2339345 and single and repeat dose derived pharmacokinetic parameters including Cmax, tmax, AUC(0-t), AUC(0-inf), and AUC(0- Ï„), as appropriate where data allow | To evaluate the systemic pharmacokinetics of single and repeat doses of inhaled GSK2339345 in healthy volunteers administered by an aqueous droplet inhaler | Approximately 5 weeks from first dose to the follow-up visit |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
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| ID | Term |
|---|---|
| D007239 | Infections |
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| ID | Term |
|---|---|
| D000077592 | Maraviroc |
| C109078 | lamivudine, zidovudine drug combination |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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| Drug |
1 tablet: lamivudine 150mg, zidovudine 300mg |
|
| GSK2838510 | Drug | Maraviroc 300mg, lamivudine 150mg, zidovudine 300mg |
|
| Identification of taste of the solution and rating on 11 point scale to rate pleasantness or unpleasantness | To assess the palatability of GSK2339345 administered by an aqueous droplet inhaler | Approximately 5 weeks from first dose to the follow-up visit |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |