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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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This will be a two-part study in healthy adults. Part A is a phase 1, non-randomized, open label, single-dose, single-centre mass balance study utilizing a radiolabeled dose to investigate the recovery, excretion, and pharmacokinetics of oral GSK1265744 in a cohort of 6 healthy adult male subjects. Subjects will undergo a pre-study screening visit within 30 days of the first dose and those who successfully pass pre-study assessments and meet eligibility criteria will be enrolled into the study to receive the equivalent of a 30 mg dose of GSK1265744 as an oral solution, containing approximately 70 microcuries (mcg Ci) [0.96 millisieverts (mSv)] of radioactivity under fasted conditions. Blood, urine and fecal samples will be collected for a maximum of 504 hours (21 days) following study drug administration. In Part B, approximately 10 healthy male and female subjects will be enrolled to evaluate the single-dose safety, tolerability and PK of supratherapeutic dose of GSK1265744 150 mg compared with placebo. Each subject will receive a single dose of GSK1265744 150 mg or placebo on Day 1 under fasting conditions in the morning. Blood, urine and fecal samples will be collected for 336 hours (14 days) following dosing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: 14C-GSK1265744 Arm | Experimental | Each subject will receive a single 30 mg oral solution dose of GSK1265744 containing 14C-GSK1265744 of approximately 70 mcgCi (0.96 MSv) of radioactivity. |
|
| Part B: GSK1265744 Arm | Experimental | In Part B - 8 subjects will be randomised to receive a single dose of GSK1265744 150 mg |
|
| Part B: Placebo Arm | Placebo Comparator | In Part B - 2 subjects will be randomised to receive a single dose of placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK1265744B (sodium salt) containing 14C-GSK1265744B | Drug | A white to slightly colored nonsterile crystalline powder for oral solution |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Percent recovery of total radioactive [14C] GSK1265744 in urine and feces. | Measurement of total radioactivity present in individual samples (plasma, urine, and feces) collected for a minimum of 336 hours (14 days) post dose up to a maximum of 504 hours (21 days). | Up to 21 days |
| Part A: Composite of plasma GSK1265744 PK parameters to access total radioactivity in blood | The PK parameters will include: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a profile [AUC (0-t)], Area under the concentration-time curve from time zero (predose) extrapolated to infinite time [AUC (0-infinity)], Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), Terminal phase elimination rate constant (lambda z), apparent terminal phase half-life (t1/2), and oral clearance (CL/F) of plasma GSK1265744 and total radioactivity in plasma and blood following single dose. | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 288, 312 and 336 hours post dose. |
| Part B: Number of participants with the use of concurrent medication as a measure of safety and tolerability | Up to 14 days | |
| Part B: Absolute values and changes over time of hematology as a measure of safety and tolerability. | Up to 14 days | |
| Part B: Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability. | Up to 14 days | |
| Part B: Absolute values and changes over time of urinalysis as a measure of safety and tolerability. | Up to 14 days | |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Blood: Plasma ratio of total drug-related material (radioactivity) | The blood: plasma ratio of total radioactivity (Cb/Cp) will be calculated at each time point by Clinical Statistics at GSK. | Up to 21 days |
| Part A: Percent of total radioactivity associated with red blood cells |
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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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| 150 mg GSK1265744B | Drug | This is GSK1265744B (sodium salt of GSK1265744), lactose monohydrate, Microcrystalline cellulose, hypromellose, sodium lauryl sulfate, croscarmellose sodium, magnesium stearate, Opadry film-coating, white OY-S-28876 tablet |
|
| Placebo | Drug | Microcrystalline cellulose, Opadry film-coating, white OY-S-28876 tablet |
|
| Part B: Absolute values and changes over time of vital signs as a measure of safety and tolerability. |
| Up to 14 days |
| Part B: Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability. | Up to 14 days |
| Part B: Number of participants with adverse events as a measure of safety and tolerability | Up to 14 days |
| Part B: Composite of plasma GSK1265744 PK parameters | Plasma GSK1265744PK parameters following a single-dose administration of 150 mg under fasted conditions will include: AUC (0-t)], AUC (0-infinity), Cmax, tmax, lambda z, t1/2, and oral clearance (CL/F) of plasma | Up to 14 days |
Percent of total radioactivity associated with red blood cells will be calculated based on radioactivity concentration in plasma and blood and hematocrit count. |
| Up to 21 days |
| Part A: Absolute values and changes over time of hematology as a measure of safety and tolerability. | Up to 21 days |
| Part A: Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability. | Up to 21 days |
| Part A: Absolute values and changes over time of urinalysis as a measure of safety and tolerability. | Up to 21 days |
| Part A: Absolute values and changes over time of vital signs as a measure of safety and tolerability. | Up to 21 days |
| Part A: Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability. | Up to 21 days |
| Part A: Number of participants with adverse events as a measure of safety and tolerability | Up to 21 days |
| ID | Term |
|---|---|
| D039682 | HIV-Associated Lipodystrophy Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D008060 | Lipodystrophy |
| D012875 | Skin Diseases, Metabolic |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C584914 | cabotegravir |
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