- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04371380
Pharmacokinetic Study of Cabotegravir and Rilpivirine Long-acting Intramuscular Injections in Healthy Adult Participants
February 14, 2022 updated by: ViiV Healthcare
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
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.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 1
Expanded Access
Available outside the clinical trial.
See expanded access record.
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
Glendale, California, United States, 91206
- GSK Investigational Site
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 48 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 blood pressure as determined by the investigator.
- Alanine transaminase (ALT) greater than 1.5 times upper limit of normal (ULN).
- Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- History of ongoing or clinically relevant seizure disorder within the previous 2 years, including participants who have required treatment for seizures within this time period. A prior history of seizure, with a seizure free period of at least 2 years, off anti-epileptics, may be considered for enrollment if the investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the medical monitor prior to enrollment.
- QT interval corrected for heart rate (QTc) greater than 450 millisecond for male participants and greater than 470 milliseconds for female participants
- A participant, who has an underlying skin disease or disorder (i.e. infection, inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria).
- A participant, who is considered to have insufficient musculature to allow safe administration of cabotegravir or rilpivirine in the opinion of the investigator will be excluded.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication to the completion of the follow-up visit unless in the opinion of the Investigator and ViiV medical monitor the medication will not interfere with the study procedures or compromise participant safety.
- Participation in the study would result in loss of blood or blood products in excess of 500 mililiter within 56 days.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.
- Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
- Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention.
- Presence of the Hepatitis B core antibody (HBcAb) should also lead to exclusion from the study even if HBsAg is negative.
- Positive pre-study drug/alcohol screen
- Positive human immunodeficiency virus (HIV) antibody test
- Regular use of known drugs of abuse
- Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of >14 units for males or >7 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (~240 milliliter) of beer, 1 glass (125 milliliter) of wine or 1 (25 milliliter) measure of spirits.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening.
- Participant, who has a tattoo or other dermatological condition overlying the thigh region which may interfere with interpretation of injection site reactions.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: OLI phase followed by Injection phase
Participants will be administered cabotegravir at a dose of 30 mg plus rilpivirine dose of 25 mg once daily with meal on Day 1 to Day 28 in OLI phase.
There will be 10 to 14 days wash out period after OLI.
This will be followed by an injection phase, wherein participants will receive 600 mg cabotegravir long acting given as one 3 milliliter (mL) IM injection plus 900 mg rilpivirine long acting given as one 3 mL IM injection on Day 1.
|
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.
Rilpivirine tablets will be off-white, round, biconvex film coated tablets with a unit dose of 25 mg and will be administered orally.
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.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum observed concentration (Cmax) for cabotegravir (injection phase)
Time Frame: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
|
Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28
|
Time of Cmax (Tmax) for cabotegravir (injection phase)
Time Frame: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
|
Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28
|
Area under the plasma concentration-time curve from time zero to time (AUC[0-t]) for cabotegravir (injection+follow-up phase)
Time Frame: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
|
Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52
|
Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC[0-infinity]) for cabotegravir (injection+follow-up phase)
Time Frame: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
|
Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52
|
Apparent terminal phase half-life (t1/2) for cabotegravir (follow-up phase)
Time Frame: One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
|
One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52
|
Absorption rate constant for cabotegravir (follow-up phase)
Time Frame: One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of cabotegravir.
|
One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52
|
Cmax for rilpivirine (injection phase)
Time Frame: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
|
Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28
|
Tmax for rilpivirine (injection phase)
Time Frame: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
|
Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22 and Day 28
|
AUC(0-t) for rilpivirine (injection+follow-up phase)
Time Frame: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
|
Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52
|
AUC(0-infinity) for rilpivirine (injection+follow-up phase)
Time Frame: Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
|
Day 1 (Pre-dose, 1 hour, 2 hours) and one post-dose sample on Day 2, Day 4, Day 5, Day 7, Day 10, Day 15, Day 17, Day 22, Day 28, Week 8, Week 12, Week 24, Week 36 and Week 52
|
t1/2 for rilpivirine (follow-up phase)
Time Frame: One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
|
One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52
|
Absorption rate constant for rilpivirine (follow-up phase)
Time Frame: One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52
|
Blood samples will be collected at indicated time points for pharmacokinetic analysis of rilpivirine.
|
One post-dose sample at Week 8, Week 12, Week 24, Week 36, and Week 52
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 16, 2020
Primary Completion (Actual)
December 26, 2021
Study Completion (Actual)
December 26, 2021
Study Registration Dates
First Submitted
April 28, 2020
First Submitted That Met QC Criteria
April 28, 2020
First Posted (Actual)
May 1, 2020
Study Record Updates
Last Update Posted (Actual)
February 15, 2022
Last Update Submitted That Met QC Criteria
February 14, 2022
Last Verified
February 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- HIV Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- HIV Integrase Inhibitors
- Integrase Inhibitors
- Rilpivirine
- Cabotegravir
Other Study ID Numbers
- 208832
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place.
Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HIV Infections
-
University of MinnesotaWithdrawnHIV Infections | HIV/AIDS | Hiv | AIDS | Aids/Hiv Problem | AIDS and InfectionsUnited States
-
University of California, San DiegoUniversity of California, Los Angeles; University of Southern California; California... and other collaboratorsCompleted
-
Gérond'ifRecruiting
-
University of California, DavisCompleted
-
University of California, San DiegoNational Center for Complementary and Integrative Health (NCCIH)CompletedHIV PositiveUnited States
-
University of ChicagoUniversity of Athens; National Development and Research Institutes, Inc.Completed
-
HIV Prevention Trials NetworkNational Institute on Drug Abuse (NIDA); National Institute of Allergy and...CompletedHIV PositiveIndonesia, Ukraine, Vietnam
-
University of ZimbabweCompleted
-
Florida International UniversityCompleted
-
Boston Children's HospitalNational Institute on Minority Health and Health Disparities (NIMHD)Completed
Clinical Trials on Cabotegravir Tablets
-
National Institute of Allergy and Infectious Diseases...Gilead Sciences; ViiV HealthcareActive, not recruitingHIV InfectionsBrazil, United States, South Africa, Peru, Thailand, Argentina, Vietnam
-
ViiV HealthcareJanssen, LPCompletedHIV InfectionsUnited States, Netherlands, Germany, Canada, Australia, Belgium, France, Spain, Ireland, Italy, United Kingdom, Austria, Japan, Switzerland
-
ViiV HealthcareJanssen Research and DevelopmentActive, not recruitingHIV InfectionsUnited States, Germany, Spain, France, Canada, Korea, Republic of, Italy, South Africa, Australia, Russian Federation, Mexico, Sweden, Argentina
-
ANRS, Emerging Infectious DiseasesNot yet recruiting
-
ViiV HealthcareCompletedInfection, Human Immunodeficiency VirusUnited States
-
ViiV HealthcareCompleted
-
ViiV HealthcareAvailableInfection, Human Immunodeficiency Virus
-
ViiV HealthcareRecruiting
-
ViiV HealthcareRecruiting
-
National Institute of Allergy and Infectious Diseases...CompletedHIV InfectionsUnited States, Malawi, Brazil, South Africa