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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
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CAB is an integrase inhibitor that is currently in Phase 2 clinical trials for the treatment and prevention of human immunodeficiency virus-1 (HIV-1) infection. RIF, a rifamycin used for treatment of tuberculosis (common co-infection in HIV-infected subjects), is a known inducer of uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) and Cytochrome P450 3A4 (CYP3A4). CAB is primarily metabolized via UGT1A1 and UGT1A9, thus a drug interaction between CAB and RIF is possible. This study will be a phase I, single-center, open label, fixed-sequence cross-over study to compare the single dose PK of CAB oral 30 milligrams (mg) when co-administered with RIF 600 mg once daily at steady-state to those of CAB oral 30 mg administered alone. Fifteen subjects are planned to be enrolled to obtain 12 evaluable subjects for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A(CAB 30mg)+B (RIF 600mg)+C (CAB 30mg and RIF 600mg) | Experimental | Subjects will receive a single dose of CAB 30 mg on day 1. Subjects will then receive RIF 600 mg once daily on days 8-28 with co-administration of a single dose of CAB 30 mg on day 21. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAB | Drug | CAB 30 mg as 1 tablet will be administered orally with 240 mL of water in the fasted state. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma CAB maximum observed concentration after single dose administration (Cmax) | Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose. | Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28 |
| Plasma CAB area under the concentration versus time from time zero to infinity after single dose administration (AUC(0-∞)) | Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose. | Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma CAB concentration at 24 hours post dose (C24) | Plasma PK samples collected at Period 1 24 hours post dose and at Period 3 24 hours post dose will be used to measure plasma CAB C24. | Days 2 and 22 |
| Plasma CAB AUC from time zero to last time point with measurable concentration after single dose administration (AUC (0-t)) |
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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 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28739783 | Derived | Ford SL, Sutton K, Lou Y, Zhang Z, Tenorio A, Trezza C, Patel P, Spreen W. Effect of Rifampin on the Single-Dose Pharmacokinetics of Oral Cabotegravir in Healthy Subjects. Antimicrob Agents Chemother. 2017 Sep 22;61(10):e00487-17. doi: 10.1128/AAC.00487-17. Print 2017 Oct. |
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| 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 |
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| RIF | Drug | RIF 600 mg as 2 capsules of 300 mg will be administered orally with 240 mL of water in the fasted state. |
|
Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose. |
| Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28 |
| Plasma CAB time of occurrence of Cmax (tmax) and terminal phase half-life (t1/2) | Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose. | Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28 |
| Plasma CAB apparent clearance following oral dosing (CL/F) | Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose. | Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28 |
| Number of subjects with adverse events (AEs) as a measure of safety and tolerability | AEs will be collected from the start of study treatment until the follow-up contact | Up to 42 days |
| Concurrent medication as a measure of safety and tolerability | Concurrent medication will be reviewed from the start of study treatment until the follow-up contact. | Up to 42 days |
| Clinical laboratory screens as a measure of safety and tolerability | Haematology, clinical chemistry, urinalysis and additional parameters will be tested. | Day -1, 8, 13, 20, 23, 25, 28, and follow-up (up to Day 42) |
| Electrocardiogram (ECG) as a measure of safety and tolerability | Day 1, 20, 21, and 23 |
| Vital signs assessments as a measure of safety and tolerability | Day 1, 8, 20, 21, 25, 26, 28, and follow-up (up to Day 42) |
| 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 |