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 30 mg tablets administered orally.
DRUGCabotegravir 400 mg/mL
CAB 400 mg/mL administered intramascularly or subcutaneously.
CAB 200 mg/mL administered intramascularly or subcutaneously.
DRUGTopical Non-steroidal anti-inflammatory drug (NSAID)
NSAID applied topically.
DRUGTopical steroid
Steroid medication applied topically.
DRUGTopical NSAID placebo
Placebo for NSAID applied topically.
rHuPH20 administered subcutaneously.
DRUGTopical steroid placebo
Placebo for steroid applied topically.
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.
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 | Description |
|---|---|---|
| Part 1 Injection 1: Time of Maximum Observed Plasma Concentration (Tmax) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b & 4h | Injection 1 - Day 1 to Week 4 | Blood samples were collected for Pharmacokinetic (PK) analysis of CAB. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
| Part 1 Injection 2: Tmax for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4 & 4b | Injection 2 - Day 1 to Week 52 follow-up | Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
| Part 2 Injection 1: Tmax for CAB 400 mg/ml Formulation for Cohort 5 | Injection 1 - Day 1 to Week 12 | Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
| Part 2 Injection 2: Tmax for CAB 400 mg/ml Formulation for Cohort 5 | Injection 2 - Day 1 to Week 52 follow-up | Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
| Part 1 Injection 2: Apparent Terminal Phase Half-life (T1/2) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4 & 4b | Injection 2 - Week 4 to Week 52 follow-up | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
| Part 2 Injection 2: T1/2 for CAB 400 mg/ml Formulation for Cohort 5 | Injection 2 - Week 12 to Week 52 follow-up | Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
| Part 1 Injection 2: Terminal Absorption Elimination Rate Constant (KALA) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4 & 4b | Injection 2 - Week 4 to Week 52 follow-up | KALA defined as the rate at which a drug is absorbed into the bloodstream after administration. Blood samples were collected at indicated time points. PK parameters were determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
| Part 2 Injection 2: KALA for CAB 400 mg/ml Formulation for Cohort 5 | Injection 2 - Week 12 to Week 52 follow-up | KALA defined as the rate at which a drug is absorbed into the bloodstream after administration. Blood samples were collected at indicated time points. PK parameters were determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
| Part 1 Injection 1: Plasma Trough Concentrations (Ctau) of CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b & 4h | Injection 1 - Day 1 to Week 4 | Blood samples were collected for PK analysis of CAB. Ctau is the trough concentration at the end of the dosing interval. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR studies. |
| Part 1 Injection 2: Ctau of CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b | Injection 2 - Day 1 to Week 4 | Blood samples were collected for PK analysis of CAB. Ctau is the trough concentration at the end of the dosing interval. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR studies. |
| Part 2 Injection 1: Ctau of CAB 400 mg/ml Formulation for Cohort 5 | Injection 1 - Day 1 to Week 12 | Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods. Ctau is the trough concentration at the end of the dosing interval. Ctau was expressed as geometric mean. For ATLAS /FLAIR: Historical data of CAB200 group, the geometric mean following dose normalization to 800mg was presented. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR and ECLAIRE studies. |
| Part 1 Injection 1: Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Time Point (AUC(0-t)) of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4, 4b and 4h | Injection 1 - Day 1 to Week 4 | Blood samples were collected for PK analysis of CAB. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
| Part 1 Injection 2: AUC(0-t) of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4 and 4b | Injection 2 - Day 1 to Week 4 | Blood samples were collected for PK analysis of CAB. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
| Part 1 Injection 1: Maximum Observed Plasma Concentration (Cmax) of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4, 4b and 4h | Injection 1 - Day 1 to Week 4 | The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
| Part 1 Injection 2: Cmax of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4, 4b | Injection 2 - Day 1 to Week 4 | The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and Part 2: Number of Participants With Adverse Events (AEs) in Injection Phase and Follow up Phase | From Injection 1 day 1 up to 52 weeks follow-up | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. The objective of this analysis is to present the data for participants that received at least an intramuscular or subcutaneous study injection of CAB 400 mg/mL or CAB 200 mg/mL with rHuPH20 formulation. |
| Part 1 and Part 2: Number of Participants With Liver Biochemistry Abnormalities in Injection Phase and Follow up Phase | From Injection 1 day 1 up to 52 weeks follow-up | Blood samples were collected at indicated timepoints to analyze the liver biochemistry parameters: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), Bilirubin and Direct Bilirubin. The objective of this analysis is to present the data for participants that received at least an intramuscular or subcutaneous study injection of CAB 400 mg/mL or CAB 200 mg/mL with rHuPH20 formulation. |
| Cmax for CAB Following Oral 30 mg Administration | Up to Day 29 | Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods. |
| Tmax for CAB Following Oral 30 mg Administration | Up to Day 29 | Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods. |
| AUC(0-t) for CAB Following Oral 30 mg Administration | Up to Day 29 | Blood samples were collected for PK analysis of CAB after subcutaneous administration. The PK parameters were calculated by non-compartmental analysis. |
| Concentration at 24 Hours (C24) for CAB Following Oral 30 mg Administration | At 24 hours | — |
| Ctau for CAB Following Oral 30 mg Administration | Up to 24 hours on day 29 (Oral lead in phase) | — |
| Cmax of CAB 200 for Cohort 4h | Injection 1 - Day 1 to Week 52 follow-up | Blood samples were collected for PK analysis of CAB after subcutaneous administration. PK parameter was determined using standard non-compartmental methods. |
| Tmax of CAB 200 for Cohort 4h | Injection 1 - Day 1 to Week 52 follow-up | Blood samples were collected for PK analysis of CAB after subcutaneous administration. PK parameter was determined using standard non-compartmental methods. |
| AUC(0-t) of CAB 200 for Cohort 4h | Injection 1 - Day 1 to Week 52 follow-up | Blood samples were collected for PK analysis of CAB after subcutaneous administration. PK parameters were determined using standard non-compartmental methods. |
| Ctau of CAB 200 for Cohort 4h and in ATLAS/FLAIR Study | Injection 1 - Day 1 to Week 52 follow-up | Blood samples were collected for PK analysis of CAB after subcutaneous administration. Ctau is the trough concentration at the end of the dosing interval. PK parameter was determined using standard non-compartmental methods. Ctau was expressed as geometric mean. For ATLAS /FLAIR: Historical data of CAB200 group, the geometric mean following dose normalization to 400mg was presented. |
| T1/2 of CAB 200 & CAB 400 for Cohort 4h | Injection 1 - Day 1 to Week 52 follow-up | Blood samples were collected for PK analysis of CAB after subcutaneous administration. The PK parameters were calculated by non-compartmental analysis. |
| KALA of CAB 200 & CAB 400 for Cohort 4h | Injection 1 - Day 1 to Week 52 follow-up | KALA defined as the rate at which a drug is absorbed into the bloodstream after administration. Blood samples were collected for PK analysis of CAB after subcutaneous administration. PK parameters were determined using standard non-compartmental methods. |
Countries
New Zealand, United States
Contacts
STUDY_DIRECTORGSK Clinical Trials
ViiV Healthcare
Participant flow
Pre-assignment details
This study consisted of an Oral Lead In (OLI) Phase (day 1 to 28), an Injection Phase, which consisted of part 1 (cohorts 1-4h) and part 2 (cohort 5), and a Follow-up Phase up to 52 weeks.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized Adult (18-64 years) | 138 Participants |
| Race/Ethnicity, Customized De-identified | 11 Participants |
| Race/Ethnicity, Customized Other, unspecified | 0 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 18 | 0 / 2 | 0 / 11 | 0 / 1 | 0 / 16 | 0 / 2 | 0 / 18 | 0 / 2 | 0 / 13 | 0 / 14 | 0 / 9 | 0 / 8 | 0 / 10 | 0 / 1 |
| other Total, other adverse events | 4 / 13 | 18 / 18 | 2 / 2 | 10 / 11 | 1 / 1 | 15 / 16 | 2 / 2 | 18 / 18 | 1 / 2 | 13 / 13 | 13 / 14 | 9 / 9 | 8 / 8 | 10 / 10 | 1 / 1 |
| serious Total, serious adverse events | 0 / 13 | 0 / 18 | 0 / 2 | 0 / 11 | 0 / 1 | 2 / 16 | 0 / 2 | 0 / 18 | 0 / 2 | 0 / 13 | 1 / 14 | 0 / 9 | 0 / 8 | 0 / 10 | 0 / 1 |
Outcome results
None listed