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This study will evaluate two new GSK1265744 sodium salt tablet formulations and provide data for selection of one of these tablet formulations for use in Phase 3. This is a single-center, randomized, two part, open-label, crossover study in healthy adult subjects. Part A is a randomized, open-label, 3-way balanced cross-over design in 24 subjects to assess the oral bioavailability of two GSK1265744 sodium salt tablet formulations relative to the current GSK1265744 sodium salt formulation being used in the phase IIb studies under fasting conditions. Part A treatment periods will be separated by a 14 day washout. After completion of Part A, preliminary PK data will be analyzed and a decision will be made based on pre-specified criteria, as to which formulation will be used to conduct Part B. Fifteen subjects who will have participated in Part A will participate in Part B and receive the selected formulation with a moderate fat meal. All treatments will be administered as single 30 mg doses of GSK1265744. Safety evaluations and serial PK samples will be collected during each treatment period. A follow-up visit will occur 10 - 14 days after the last dose of study drug.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A | Experimental | In Part A, subjects will be randomized to receive two new formulations of GSK1265744 30 mg (New formulation 1 -micronized [B], New formulation 2un-micronized [C]) and the sodium salt reference formulation 30 mg (Reference formulation [A]) in one of six sequences; ABC, BCA, CAB, BAC, ACB, CBA in three treatment periods under fasting condition. |
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| Part B | Experimental | Fifteen eligible subjects completing the Part A of the study will enter in to Part B where they will receive either formulation B or C. The selected drug (B or C) will be administered under fed (moderate fat meal) condition in the fourth treatment period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK1265744 Reference formulation | Drug | GSK1265744 (micronized) reference formulation is available as 30 mg tablet to be orally administered with 240 mL of water |
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| Measure | Description | Time Frame |
|---|---|---|
| Part A: Composite of pharmacokinetic (PK) parameters to evaluate the relative bioavailability of GSK1265744 in the fasted state | PK parameters will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]), AUC from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC[0-t]), maximum observed concentration (Cmax) and concentration at 24h post-dose (C24) | Pre-dose, 0.5 hour(hr), 1hr, 2hrs, 3 hrs, 4 hrs, 6hrs, 8hrs, 12hrs, 24hrs (Day 2), 48hrs (Day 3), 72hrs (Day 4), 120hrs (Day 6) and 168hrs (Day 8) post dose |
| Part B: Composite of PK parameters to evaluate the relative bioavailability of GSK1265744 in the fed state | PK parameters will include AUC(0-infinity), AUC(0-t), Cmax and C24 | Pre-dose, 0.5 hr, 1hr, 2hrs, 3 hrs, 4 hrs, 6hrs, 8hrs, 12hrs, 24hrs (Day 2), 48hrs (Day 3), 72hrs (Day 4), 120hrs (Day 6) and 168hrs (Day 8) post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Composite of other PK parameters following administration of GSK1265744 in the fasted state | Other PK parameters will include apparent terminal phase half-life (t1/2), absorption lag time (tlag), time to Cmax (tmax), the percentage of AUC(0-infinity) obtained by extrapolation (%AUCex), time of last measurable concentration (tlast) and apparent oral clearance (CL/F) | Pre-dose, 0.5hr, 1hr, 2hrs, 3 hrs, 4 hrs, 6hrs, 8hrs, 12hrs, 24hrs (Day 2), 48hrs (Day 3), 72hrs (Day 4), 120hrs (Day 6) and 168hrs (Day 8) post dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | ViiV Healthcare | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Overland Park | Kansas | 66211 | United States |
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| GSK1265744 New formulation 1 | Drug | GSK1265744 (micronized) New formulation 1 is available as 30 mg tablet to be orally administered with 240 mL of water |
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| GSK1265744 New formulation 2 | Drug | GSK1265744 (un-micronized) New formulation 2 is available as 30 mg tablet to be orally administered with 240 mL of water |
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| Part A: Safety and tolerability parameters, including adverse events, concurrent medication, clinical laboratory screens, ECG, and vital signs assessments | Clinical laboratory screens will include haematology, clinical chemistry and urinalysis. Vital sign assessment will include systolic and diastolic blood pressure and heart rate | Up to 13 weeks |
| Part B: Composite of other PK parameters following administration of GSK1265744 in the fed state | Other PK parameters will include t1/2, tlag, tmax, %AUCex, tlast and CL/F | Pre-dose, 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs (Day 2), 48hrs (Day 3), 72hrs (Day 4), 120hrs (Day 6) and 168hrs (Day 8) post dose |
| Part B: Safety and tolerability parameters will include adverse events, concurrent medication, clinical laboratory screens, ECG, and vital signs assessments | Clinical laboratory screens will include haematology, clinical chemistry and urinalysis | Up to 18 weeks |
| ID | Term |
|---|---|
| D007239 | Infections |
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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