Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02951052 | Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current Antiretroviral Regimen in Virologically Suppressed HIV-1-infected Adults | PHASE3 | ACTIVE NOT_RECRUITING | 618 | — | — | Oct 28, 2016 | Dec 31, 2029 | Dec 31, 2025 | 113 | United States, Argentina +11 |
| NCT03149848 | Effect of Rifabutin on the Pharmacokinetics of Oral Cabotegravir in Healthy Subjects | PHASE1 | COMPLETED | 15 | — | — | Jun 6, 2017 | Sep 7, 2017 | Sep 17, 2020 | 1 | United Kingdom |
| NCT02799264 | A Study to Evaluate the Effect of High Fat Meal on Cabotegravir | PHASE1 | COMPLETED | 24 | — | — | Jun 1, 2016 | Aug 1, 2016 | Jan 13, 2017 | 1 | United States |
| NCT02345707 | Relative Bioavailability Study of Phase III Tablet Formulation of Cabotegravir | PHASE1 | COMPLETED | 37 | — | — | Mar 1, 2015 | Jun 1, 2015 | Jul 13, 2015 | 1 | United States |
Number of participants with virologic failure endpoint (HIV-1 RNA\>=50 c/mL) as per Food and Drug Administration (FDA) snapshot algorithm at Week 48 was assessed to demonstrate the non-inferior antiviral activity of switching to intramuscular (IM) CAB LA+RPV LA every 4 weeks compared to continuation of current ART regimen over 48 weeks in HIV-1 infected ART-experienced participants. The HIV-1 RNA \>=50 copies/mL per snapshot algorithm was determined by the last available on-treatment HIV-1 RNA measurement within the analysis visit window of interest.
Blood samples for PK analysis of CAB were collected at pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28. AUC (0 to tau) was calculated using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. PK Summary Population included participants who had CAB PK parameter estimates from both serial PK sampling time periods 1 and 2. Comparisons were made for the repeated dose PK parameters of CAB when given alone in Period 1 and when co-administered with steady-state RBT in Period 2.
Blood samples for PK analysis of CAB were collected at pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28. Cmax was determined directly from the concentration-time data. Comparisons were made for the repeated dose PK parameters of CAB when given alone in Period 1 and when co-administered with steady-state RBT in Period 2.
AUC (0 infinity\[inf\]) is defined as the area under cabotegravir plasma concentration time curve from time zero (pre dose) extrapolated to infinite time.
AUC (0-t) is defined as area under cabotegravir plasma concentration time curve from time zero (pre dose) to the last time of quantifiable concentration.
Cmax is defined as the maximum observed plasma concentration of cabotegravir.
C24 is defined as the plasma concentration at 24 hours after administration of cabotegravir.
To evaluate the relative bioavailability of cabotegravir after single 30 mg dose in the fasted state, the following PK parameters will be assessed: 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 within a subject across all treatments (AUC (0-t)), maximum observed concentration (Cmax) and concentration at 24 hours post-dose (C24)
| Arm | Type | Description |
|---|---|---|
| CAB LA + RPV LA every 4 weeks | EXPERIMENTAL | Eligible subjects receive Oral CAB 30 mg + RPV 25 mg once daily for four weeks, IM CAB LA 600 mg and RPV LA 900 mg for the first injection, and Week 4 onwards subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks until withdrawal. |
| Current antiretroviral regimen | ACTIVE_COMPARATOR | Eligible subjects will continue their current anti-retroviral regimen (2 NRTIs plus an INI, NNRTI, or a PI) for 52 weeks. After 52 weeks subjects have the option to continue study participation by switching to CAB LA + RPV LA in the Extension Phase where they will follow the procedure of CAB LA + RPV LA arm. |
| Treatment A | EXPERIMENTAL | Participants will be administered a single oral dose of CAB 30 mg after an overnight fast of at least 6 hours for 14 days in Period 1. Dosing of study medication on non-PK days may be with or without food. |
| Treatment B | EXPERIMENTAL | Participants will be administered a single dose of RBT 300 mg and a single dose of CAB 30 mg after an overnight fast of at least 6 hours once daily for 14 days in Period 2. Dosing of study medication on non-PK days may be with or without food. |
| Cabotegravir 30 mg: Sequence AB (fasted followed by fed) | EXPERIMENTAL | There will be two administration periods with 14 days of wash out. In Period 1, eligible subjects will receive a single tablet of cabotegravir 30 mg,(micronized 500 mg core weight) orally under fasted condition with at least 10 hours of prior fast. In Period 2, eligible subjects will receive single tablet of cabotegravir 30 mg, micronized 500 mg core weight orally following a high fat meal. Blood samples will be withdrawn from subjects prior to dosing and upto 8 days after the last dose of cabotegravir. |
| Cabotegravir 30 mg: Sequence BA (fed followed by fasted) | EXPERIMENTAL | There will be two administration periods with 14 days of wash out. In Period 1, eligible subjects will receive single tablet of cabotegravir 30 mg, micronized 500 mg core weight orally following a high fat meal. In Period 2, eligible subjects will receive a single tablet of cabotegravir 30 mg, micronized 500 mg core weight orally under fasted condition with at least 10 hours of prior fast. Blood samples will be withdrawn from subjects prior to dosing and upto 8 days after the last dose of cabotegravir. |
| Part A | EXPERIMENTAL | Subjects will receive reference cabotegravir 30 mg current formulation (Treatment A), Cabotegravir 30 mg micronized new formulation 500 M (Treatment B) and Cabotegravir 30 mg unmicronized new formulation 500 U (Treatment C) in one of six sequences ABC, ACB, BCA, BAC, CAB, CBA in three treatment periods under fasting condition |
| Part B | EXPERIMENTAL | Subjects will receive reference Cabotegravir 30 mg current formulation (Treatment A), Cabotegravir 30 mg micronized new formulation 650 M (Treatment D) and Cabotegravir 30 mg unmicronized new formulation 650 U (Treatment E) in one of six sequences ADE, AED, DAE, DEA, EAD, EDA in three treatment periods under fasting condition |
| Name | Type | Description |
|---|---|---|
| Cabotegravir (CAB) tablet | DRUG | It is a white oval shaped film coated 30 mg tablets for oral administration. CAB Tablet is composed of cabotegravir sodium, lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycolate, magnesium stearate, and white film-coat |
| Rilpivirine (RPV) tablet | DRUG | It is a 25 mg tablet with off-white, round, biconvex, film-coated and debossed on one side with "TMC" and the other side with "25". Each tablet contains RPV hydrochloride, and the inactive ingredients croscarmellose sodium, lactose monohydrate, magnesium stearate, polysorbate 20, povidone K30 and silicified microcrystalline cellulose |
| Cabotegravir - Injectable Suspension (CAB LA) | DRUG | It is a sterile white to slightly pink suspension containing 200 mg/mL of CAB as free acid for administration by intramuscular (IM) injection. Each vial is for single-dose use containing a withdrawable volume of 2.0 mL, and does not require dilution prior to administration. CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol 3350, mannitol, and water for injection |
| Rilpivirine - Injectable Suspension (RPV LA) | DRUG | It is a sterile white suspension containing 300 mg/mL of RPV as the free base. The route of administration is by intramuscular (IM) injection. Each vial contains a nominal fill of 2.0 mL, and does not require dilution prior to administration. RPV LA requires refrigeration and must be protected from light. RPV LA is composed of RPV free base, poloxamer 338, sodium dihydrogen phosphate monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water for injection. |
| 2 NRTIs plus an INI, NNRTI, or PI | DRUG | Acceptable stable (initial or second) ARV regimens include 2 NRTIs plus: * INI with the exception of ABC/DTG/3TC (either the initial or second cART regimen) * NNRTI (either the initial or second cART regimen) * Boosted PI (or atazanavir \[ATV\] unboosted) (either the initial or second PI-based cART regimen) |
| Cabotegravir | DRUG | It will be available as a white aquarius film coated tablet for oral administration. CAB Tablet is composed of GSK1265744B (micronized) lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycolate, magnesium stearate |
| Rifabutin | DRUG | It will be available as an opaque red-brown hard gelatin capsules containing 150 mg of rifabutin for oral administration. These capsules are composed of rifabutin, microcrystalline cellulose, sodium lauryl sulphate, magnesium stearate, and silica gel |
| Cabotegravir 30 mg | DRUG | Cabotegravir (GSK1265744B ) is available as white to almost white, oval shaped, film coated tablet, of weight 515 mg. The tablet contains micronized cabotegravir, lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycolate, and magnesium stearate. Each tablet is equivalent to 30 mg cabotegravir and needs to be taken orally with 240 mL of water. Cabotegravir tablet will be administered to subjects either in fasting condition or following a high fat meal. |
| Cabotegravir 30 mg current formulation | DRUG | Cabotegravir 30 mg current formulation (Treatment A) is a film coated tablet with a weight of 824 mg |
| Cabotegravir 30 mg micronized new formulation 500 M | DRUG | Cabotegravir 30 mg micronized new formulation 500 M (Treatment B) is a film coated tablet with a weight of 515 mg |
| Cabotegravir 30 mg unmicronized new formulation 500 U | DRUG | Cabotegravir 30 mg unmicronized new formulation 500 U (Treatment C) is a film coated tablet with a weight of 515 mg |
| Cabotegravir 30 mg micronized new formulation 650 M | DRUG | Cabotegravir 30 mg micronized new formulation 650 M (Treatment D) is a film coated tablet with a weight of 670 mg |
| Cabotegravir 30 mg unmicronized new formulation 650 U | DRUG | Cabotegravir 30 mg unmicronized new formulation 650 U (Treatment E) is a film coated tablet with a weight of 670 mg |
Inclusion Criteria: * Aged 18 years or older (or ≥19 where required by local regulatory agencies), at the time of signing the informed consent. * Must be on uninterrupted current regimen (either the initial or second ARV regimen) for at least 6 months prior to Screening. Any prior switch, defined a...