HIV Infections
Conditions
Keywords
Pharmacokinetics, Safety, Tolerability, Cabotegravir, VH4367310, Healthy adults
Brief summary
This study evaluates the PK, safety, and tolerability of a single increasing dose of VH4367310, a cabotegravir (CAB) prodrug, when administered intramuscularly in healthy adult participants 18 to 55 years of age.
Interventions
DRUGVH4367310
VH4367310 will be administered intramuscularly.
DRUGPlacebo
Placebo will be administered intramuscularly.
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be greater than or equal to (\>=) 18 years and less than or equal to (\<=) 55 years of age, at the time of signing the informed consent. * Participants who are overtly healthy as determined by medical evaluation. * Body weight \>=40 kg and BMI within the range \>=18 to \<=32 kg/m\^2. * Participants may be male or female. Male participants are eligible to participate if they agree to the contraception requirements of the study during the study intervention period and for at least 90 days after the last dose of study intervention. Participants assigned female at birth are eligible to participate if they are a participant of non-childbearing potential (PONCBP). * Capable of giving written informed consent.
Exclusion criteria
* Current presence or history of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological 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. * Any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. * Unstable liver disease or known hepatic or biliary abnormalities. * History of clinically relevant hepatitis within last 6 months. * History of cirrhosis with or without viral hepatitis co-infection. * Participants determined by the investigator to have a high risk of seizures. * Participant who poses a significant suicidality risk. * Current or anticipated need for chronic anti-coagulation therapy. * Hereditary coagulation or platelet disorders. * Any acute laboratory abnormality at screening that would preclude participation or exclusionary laboratory value. * Abnormal blood pressure. * ALT \>1.5x upper limit of normal (ULN). Total bilirubin \>1.5x ULN; Participants with Gilbert's syndrome can be included with total bilirubin \>1.5x ULN as long as direct bilirubin is \<=1.5x ULN. * Hemoglobin \<12.5 g/dL for men and \<11 g/dL for women. * Creatinine clearance (eGFR) of \<60 millilitre per minute (mL/min)/1.73 square meter (m\^2). * Presence of HbsAg and/or HbcAb 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 HIV antibody/antigen test (HIV-1 ± HIV-2). * Current enrolment or past participation in another investigational study in which an experimental drug or experimental vaccine was administered. * Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication. * Participation in the study would result in loss of blood or blood products in excess of 500 mL within 56 days. * Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day. * Past participation in another investigational clinical study in which long-acting CAB was administered or any CAB use for pre-exposure prophylaxis (PrEP). * History of sensitivity to any of the study interventions (or components thereof), a history of drug allergy or another allergy. * Participant has an implant/enhancement (including fillers); or tattoo or other dermatological condition overlying the area for IM or SC injection or any other area which may significantly interfere with interpretation of injection site reactions. * History of or ongoing high-risk behaviors that may put the participant at increased risk for HIV. * 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. * Regular use of known drugs of abuse. * Positive pre-study drug/alcohol screen. * Cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. Any other clinical condition, behaviour or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration time curve from time zero to last quantifiable time point (AUC0-tlast) of VH4367310 and CAB | Up to Week 72 | — |
| Maximum observed plasma concentration (Cmax) of VH4367310 and CAB | Up to Week 72 | — |
| Time to maximum observed plasma concentration (Tmax) of VH4367310 and CAB | Up to Week 72 | — |
| Number of participants with drug-related adverse events (AEs) | Up to Week 72 | 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. |
| Number of participants with AEs as per severity | Up to Week 72 | Severity is graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading criteria, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = Death. |
| Number of participants with drug-related serious adverse events (SAEs) | Up to Week 72 | An SAE is defined as any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongs existing hospitalization, results in disability/incapacity or other medically significant events. |
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed