HIV Infections
Conditions
Keywords
Cabotegravir, Long-Acting Injection, Pharmacokinetics, Safety, Tolerability
Brief summary
This is an active control, randomized study to investigate the safety, tolerability and PK of repeat dose administration of long-acting CAB 400 mg/mL formulation intramuscular (IM) (gluteus medius and vastus lateralis) and subcutaneous (SC) (abdominal) injections in healthy adult participants.
Interventions
DRUGCabotegravir sodium (Oral Lead In)
CAB will be available as 30 mg tablets for oral administration.
DRUGCabotegravir 400 mg/mL
CAB 400 mg/mL will be available for administration by IM injection or SC Injection.
CAB 200 mg/mL will be available for administration by IM injection or SC Injection.
DRUGTopical non-steroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drug will be available for topical application
DRUGTopical steroid
Steroid will be available for topical application
DRUGPlacebo creams/gels
Placebo creams/gels will be available for topical application
rHuPH20 will be available for administration by SC Injection
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This will be a double-blind (sponsor-unblind) study.
Intervention model description
Participants will receive repeat doses of long-acting CAB 400 mg/mL or CAB 200 mg/mL at four-weekly (Q4W) interval in Part 1 and at 12-weekly (Q12W) interval in Part 2.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent. * Participants who are overtly healthy as determined by medical evaluation. * A participant with a clinical abnormality or laboratory parameters which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included if the investigator determines and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Participants who are negative on two consecutive tests for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), performed at Screening and within 5 days of admission to the Phase I unit, using an approved molecular test (Polymerase chain reaction \[PCR\]). * Body weight more than or equal to (\>=)40 kilogram (kg) and body mass index (BMI) within the range 18 to 32 kilogram per square meter (kg/m\^2). * Male participants are eligible to participate if they agree to use contraceptive methods and refrain from donating sperm. * A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of less than (\<)1 percent(%). * Capable of giving signed informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Geometric mean ratio of Plasma AUC(0-t) of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b | At Injection 2 Week 4 |
| Ctau for cabotegravir (Part 1 Injection 2) | Injection 2 Day 1 to Injection 2 Week 4 |
| Ctau for cabotegravir (Part 2 Injection 1) | Injection 1 Day 1 to Injection 1 Week 12 |
| Ctau for cabotegravir (Part 2 Injection 2) | Injection 2 Day 1 to Injection 2 Week 12 |
| Apparent terminal phase half-life (T1/2) for cabotegravir (Part 1 Injection 2) | Injection 2 Week 4 to Week 52 follow-up |
| T1/2 for cabotegravir (Part 2 Injection 2) | Injection 2 Week 12 to Week 52 follow-up |
| Geometric mean ratio of plasma Ctau of CAB for Cohorts 1,2,3,4, 4b & 4h at Week4 (Part 1 Injection 1) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 8 Ctau following first injection at Week 4 in ATLAS [201585]/FLAIR [201584]Study) | At Injection 1 Week 4 |
| Geometric mean ratio of plasma Ctau of CAB for Cohorts 1,2,3,4, 4b at Week 4 (Part 1 Injection 2) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 12 Ctau following first injection at Week 8 in ATLAS [201585]/FLAIR [201584]Study) | At Injection 2 Week 4 |
| Geometric mean ratio of plasma Ctau of CAB for Cohorts 5 and 6 at Week 12(Part 2 Injection 1) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 8 Ctau following first injection at Week 4 in ATLAS [201585]/FLAIR [201584]Study) | At Injection 1 Week 12 |
| Geometric mean ratio of plasma trough concentration (Ctau) of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h | At Injection 1 Week 4 |
| Geometric mean ratio of plasma trough concentration (Ctau) of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b | At Injection 2 Week 4 |
| Geometric mean ratio of Plasma AUC(0-t) of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h | At Injection 1 Week 4 |
| Geometric mean ratio of Plasma Cmax of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b | At Injection 2 Week 4 |
| Geometric mean ratio of Plasma Cmax of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h | At Injection 1 Week 4 |
| Absorption rate constant (KALA) for cabotegravir (Part 1 Injection 2) | Injection 2 Week 4 to Week 52 follow-up |
| KALA for cabotegravir (Part 2 Injection 2) | Injection 2 Week 12 to Week 52 follow-up |
| Maximum observed Plasma concentration (Cmax) for cabotegravir (Part 1 Injection 1) | Injection 1 Day 1 to Injection 1 Week 4 |
| Cmax for cabotegravir (Part 1 Injection 2) | Injection 2 Day 1 to Week 52 follow-up |
| Cmax for cabotegravir (Part 2 Injection 1) | Injection 1 Day 1 to Injection 1 Week 12 |
| Cmax for cabotegravir (Part 2 Injection 2) | Injection 2 Day 1 to Week 52 follow-up |
| Time of maximum observed plasma concentration (Tmax) for cabotegravir (Part 1 Injection 1) | Injection 1 Day 1 to Injection 1 Week 4 |
| Tmax for cabotegravir (Part 1 Injection 2) | Injection 2 Day 1 to Week 52 follow-up |
| Tmax for cabotegravir (Part 2 Injection 1) | Injection 1 Day 1 to Injection 1 Week 12 |
| Tmax for cabotegravir (Part 2 Injection 2) | Injection 2 Day 1 to Week 52 follow-up |
| Area under the concentration - time curve from time zero to last quantifiable time point (AUC[0-t]) for cabotegravir (Part 1 Injection 1) | Injection 1 Day 1 to Injection 1 Week 4 |
| AUC(0-t) for cabotegravir (Part 1 Injection 2) | Injection 2 Day 1 to Injection 2 Week 4 |
| AUC(0-t) for cabotegravir (Part 2 Injection 1) | Injection 1 Day 1 to Injection 1 Week 12 |
| AUC(0-t) for cabotegravir (Part 2 Injection 2) | Injection 2 Day 1 to Injection 2 Week 12 |
| Trough concentrations (Ctau) for cabotegravir (Part 1 Injection 1) | Injection 1 Day 1 to Injection 1 Week 4 |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants with liver biochemistry abnormalities | Up to 52 weeks follow-up |
| Cmax for cabotegravir following oral 30 mg administration | Up to Day 29 |
| Tmax for cabotegravir following oral 30 mg administration | Up to Day 29 |
| AUC(0-t) for cabotegravir following oral 30 mg administration | Up to Day 29 |
| Concentration at 24 hours (C24) for cabotegravir following oral 30 mg administration | At 24 hours |
| Ctau for cabotegravir at Day 29 following oral 30 mg administration | Up to Day 29 |
| Cmax of cabotegravir for cohort 4h | Injection 1 Day 1 to Week 52 follow-up |
| Tmax of cabotegravir for cohort 4h | Injection 1 Day 1 to Week 52 follow-up |
| AUC(0-t) of cabotegravir for cohort 4h | Injection 1 Day 1 to Week 52 follow-up |
| Ctau of cabotegravir for cohort 4h | Injection 1 Day 1 to Week 52 follow-up |
| T1/2 of cabotegravir for cohort 4h | Injection 1 Day 1 to Week 52 follow-up |
| KALA of cabotegravir for cohort 4h | Injection 1 Day 1 to Week 52 follow-up |
| Parts 1 and 2: Number of participants with adverse events (AEs) | Up to 52 weeks follow-up |
Countries
New Zealand, United States
Outcome results
None listed