Phase 1
Completed N=15
Pharmacokinetic Study of Cabotegravir and Rilpivirine Long-acting Intramuscular Injections in Healthy Adult Participants
Source: ClinicalTrials.gov NCT04371380 ↗Enrolled (actual)
15
Serious AEs
0.0%
Results posted
Apr 2024
Primary outcomePrimary: Maximum Observed Concentration (Cmax) of Cabotegravir (CAB) Following Single IM Injection — 3.38 Microgram per milliliter (ug/mL)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Concentration (Cmax) of Cabotegravir (CAB) Following Single IM Injection |
3.38 | — |
| PRIMARY Cmax of Rilpivirine (RPV) Following Single IM Injection |
93.5 | — |
| PRIMARY Time of Cmax (Tmax) of CAB Following Single IM Injection |
167 | — |
| PRIMARY Tmax of RPV Following Single IM Injection |
131 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time (AUC[0-t]) of CAB Following Single IM Injection |
3612 | — |
| PRIMARY AUC(0-t) of RPV Following Single IM Injection |
143891 | — |
| PRIMARY AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) of CAB Following Single IM Injection |
3948 | — |
| PRIMARY AUC(0-infinity) of RPV Following Single IM Injection |
171953 | — |
| PRIMARY Apparent Terminal Phase Half-life (t1/2) of CAB Following Single IM Injection |
21.4 | — |
| PRIMARY t1/2 of RPV Following Single IM Injection |
137 | — |
| PRIMARY Geometric Mean of Absorption Rate Constant (KALA) of CAB Following Single IM Injection |
0.00135 | — |
| PRIMARY Geometric Mean of Absorption Rate Constant (KALA) of RPV Following Single IM Injection |
0.000211 | — |
| SECONDARY Number of Participants With Liver Related Adverse Events (AEs) |
0; 0; 0 | — |
| SECONDARY Number of Participants With Liver Related Abnormalities |
0; 0; 0 | — |
Eligibility Criteria
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.
Exclusion Criteria
- Signs and symptoms which in the opinion of the investigator are suggestive of COVID-19 (example; fever, cough etc) within 14 days of inpatient admission
- Contact with known COVID-19 positive person/s in the 14 days prior to inpatient admission
- History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
- Abnormal
Data sourced from ClinicalTrials.gov (NCT04371380). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.