Pharmacokinetic Study of Cabotegravir and Rilpivirine Long-acting Intramuscular Injections in Healthy Adult Participants

A Phase 1, Open-Label Study to Evaluate the Pharmacokinetics and Tolerability of Cabotegravir and Rilpivirine Long-Acting Injections Following Intramuscular Administration in the Vastus Lateralis Muscle of Healthy Adult Participants

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04371380

Enrollment

Registered

2020-05-01

Start date

2020-09-16

Completion date

2021-12-26

Last updated

2024-04-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV Infections

Keywords

cabotegravir, rilpivirine, HIV, Pharmacokinetics, intramuscular injection

Brief summary

This is a phase 1, open label study in healthy participants to assess the pharmacokinetics of cabotegravir and rilpivirine in plasma following the administration of a single 600 milligram (mg) and a 900 mg intramuscular (IM) injection respectively, to separate vastus lateralis muscles on each leg. Cabotegravir is an integrase inhibitor being developed in combination with rilpivirine, a non-nucleoside reverse transcriptase inhibitor, for the treatment of human immunodeficiency virus (HIV). The objective is to evaluate pharmacokinetics, tolerability, and safety of cabotegravir long acting plus rilpivirine long acting administered concomitantly as two separate IM injections in the vastus lateralis muscle of adult healthy participants. The screening phase will be of 30 days, oral lead-in (OLI) phase of 28 days, there will be washout period of 10-14 days, followed by an injection phase and follow-up period will be up to 52-weeks. Approximately 15 adult healthy participants will be enrolled.

Interventions

DRUGCabotegravir Tablets

Cabotegravir tablets will be white to almost white oval shaped film coated tablets with a unit dose of 30 mg and will be administered orally.

DRUGRilpivirine Tablets

Rilpivirine tablets will be off-white, round, biconvex film coated tablets with a unit dose of 25 mg and will be administered orally.

DRUGCabotegravir extended release suspension for injection (long-acting)

Cabotegravir long-acting will be a sterile white to slightly pink suspension containing 200 mg per mL of GSK1265744 as free acid for administration by intramuscular injection.

DRUGRilpivirine extended release suspension for injection (long-acting)

Rilpivirine long-acting will be a sterile white suspension containing 300 mg per mL of rilpivirine as the free base for administration by intramuscular injection.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Masking description

This is an open label study

Intervention model description

Eligible participants will receive orally, tablets of cabotegravir plus rilpivirine for 28 days. There will be 10 to 14 days wash out period followed by an IM injection of cabotegravir long-acting plus rilpivirine long-acting.

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 including medical history, physical examination, laboratory tests, and cardiac monitoring. * A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or

Exclusion criteria

, outside the reference range may be included only if the investigator in consultation with the medical monitor agree and document that the finding is unlikely to introduce additional risk and will not interfere with the study procedures. A single repeat of a procedure or laboratory parameter is allowed to determine eligibility. * Participants who are negative on two consecutive tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), performed at Screening and on Day -1 of admission to the Phase I unit, using an approved molecular test (polymerase chain reaction or antigen test). * Body weight \>=40 kilogram (Kg) and body mass index (BMI) within the range 18 to 35 kg per square meter (inclusive). * Male or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants: Male participants are eligible to participate if they agree to the following during the intervention period and for at least 52 weeks after the last dose of study intervention; refrain from donating sperm plus either be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception/barrier as detailed; agree to use a male condom when having sexual intercourse with a woman of childbearing potential who is not currently pregnant, agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person. Female participants: 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 (%,) during the intervention period and for atleast 52 weeks after the last dose of study intervention; the investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention; a WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 30 days of the first dose of study intervention, if a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive; the investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form.

Design outcomes

Primary

Measure	Time frame	Description
Geometric Mean of Absorption Rate Constant (KALA) of RPV Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for PK analysis of RPV.
t1/2 of RPV Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for PK analysis of RPV.
Geometric Mean of Absorption Rate Constant (KALA) of CAB Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for PK analysis of CAB.
Cmax of Rilpivirine (RPV) Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for PK analysis of RPV.
Maximum Observed Concentration (Cmax) of Cabotegravir (CAB) Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of CAB.
Time of Cmax (Tmax) of CAB Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for PK analysis of CAB.
Tmax of RPV Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for PK analysis of RPV.
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time (AUC[0-t]) of CAB Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for PK analysis of CAB.
AUC(0-t) of RPV Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for PK analysis of RPV.
AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) of CAB Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for PK analysis of CAB.
AUC(0-infinity) of RPV Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for PK analysis of RPV.
Apparent Terminal Phase Half-life (t1/2) of CAB Following Single IM Injection	Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52	Blood samples were collected at indicated time points for PK analysis of CAB.

Secondary

Measure	Time frame	Description
Number of Participants With Liver Related Abnormalities	Up to 56 weeks	Blood samples were collected to assess abnormalities related to liver.
Number of Participants With Liver Related Adverse Events (AEs)	Up to 56 weeks	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

Countries

United States

Participant flow

Pre-assignment details

Fifteen participants were enrolled in the study. All the 15 participants received treatment in Oral Lead-in Phase. 14 out of 15 participants received treatment in Injection Phase. All the 14 participants in Injection phase completed the follow up phase.

Participants by arm

Arm	Count
All Enrolled Participants Participants who signed the informed consent form and received at least 1 dose of study drug.	15
Total	15

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Oral Lead-in Phase (Up to Day 28)	Physician Decision	1	0	0

Baseline characteristics

Characteristic	All Enrolled Participants
Age, Continuous	34.3 YEARS STANDARD_DEVIATION 7.72
Race/Ethnicity, Customized Asian	1 Participants
Race/Ethnicity, Customized Black or African American	7 Participants
Race/Ethnicity, Customized White	7 Participants
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	9 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 15	0 / 14	0 / 14
other Total, other adverse events	3 / 15	14 / 14	2 / 14
serious Total, serious adverse events	0 / 15	0 / 14	0 / 14