A Safety, Tolerability, Acceptability, and Pharmacokinetic (PK) Study of Cabotegravir (CAB) in Healthy Human Immunodeficiency Virus (HIV)-Uninfected Chinese Men

ViiV Healthcare48 enrolled

Overview

The pre-exposure prophylaxis (PrEP) is an important component in the overall strategy for prevention of HIV infection. Cabotegravir (CAB) is an integrase strand transfer inhibitor currently in development for treatment and prevention of HIV infection. CAB possesses attributes that allow formulation and delivery as a LA parenteral product. CAB is being developed as both oral and long acting (LA) injectable formulations. This study is designed to evaluate the PK, safety, tolerability, and acceptability of CAB LA in adult HIV uninfected Chinese male subjects at low risk for HIV acquisition. Eligible subjects will receive oral CAB during oral phase of the study followed by CAB LA intramuscular (IM) injection during injection phase of the study. Approximately 60 subjects will be screened, of which, approximately 48 subjects will enter the oral phase and 40 subjects will enter the injection phase of the study. The maximum study duration will be approximately 89 weeks including oral phase, injection phase and follow-up phase.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV Infections

Interventions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Subjects must be 18 to 65 years of age inclusive, at the time of signing the informed consent. * Subjects are male at birth. * Subjects who have non-reactive point of care (POC) HIV test and undetectable HIV-1 ribose nucleic acid (RNA) at screening. * At risk of acquiring HIV, defined as having at least one casual male or female sex partner in the past 24 months. * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring at the time of screening. * Capable of giving written informed consent. * Agree to appropriate use of contraceptive measures during heterosexual intercourse. All subjects should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (example given (e.g.), male condom) to reduce the risk of sexually transmitted infections. * Willing to undergo all required study procedures. Exclusion Criteria: * 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 the following cardiac diseases: myocardial infarction, congestive heart failure, documented hypertrophic cardiomyopathy, sustained ventricular tachycardia. * Active skin disease or disorder (that is \[i.e.\], infection, inflammation, dermatitis, eczema, drug rash, psoriasis, urticaria). Mild cases of localized acne or folliculitis or other mild skin condition may not be exclusionary at the discretion of the Investigator of Record or Medical Monitor. * Subjects determined by the Investigator to have a high risk of seizures, including subjects with an unstable or poorly controlled seizure disorder. A subject with a prior history of seizure may be considered for enrolment 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 enrolment. * Any medical condition, including psychiatric conditions that in the judgment of the investigator would interfere with the subject's ability to complete study procedures. * Subjects who, in the investigator's judgment, poses a significant suicide risk. * Use of antiretroviral (ARV) therapy (e.g., for Post exposure prophylaxis \[PEP\] or PrEP) in the past 30 days. * Use of high dose aspirin or any other anticoagulant or antiplatelet medication that would interfere with the ability to receive IM injections. * Assessed by the Investigator of Record or designee as being at "high risk" for HIV infection. This may include one or more of the following: the negative partner in an HIV serodiscordant couple where the HIV infected partner is not suppressed; men who exchange sex for goods or money; men who have engaged in any condomless anal intercourse within the past 6 months; men who have had greater than 5 male or female sexual partners within the past 6 months; men who have had a sexually transmitted disease within the past 6 months; any other behavior assessed by the investigator as "high risk". * History of drug or alcohol consumption that in the opinion of the Principal Investigator will interfere with study participation. * Ongoing intravenous drug use - episodic use or any use in the past 90 days is exclusionary (as assessed by the study investigator). * One or more reactive HIV test results at screening or enrolment, even if HIV infection is not confirmed. Negative HIV RNA must also be documented at screening. * Co-enrolment in any other HIV interventional research study (provided by self-report or other available documentation) or prior enrolment and receipt of the active arm (i.e., NOT a placebo) of a HIV vaccine trial (provided by available documentation). * Any of the following laboratory values during the screening period: positive hepatitis C antibody result; positive Hepatitis B surface antigen (HBsAg); hemoglobin \<11 grams per deciliter (g/dL); absolute neutrophil count \<750 cells/ cubic millimeter (mm\^3); platelet count \<=100,000 cells/mm\^3; presence of a coagulopathy as defined by an international normalized ratio(INR)\>1.5 or a partial thromboplastin time (PTT) \>45 seconds; calculated creatinine clearance \<60 milliliter/minute (mL/minute) using the Cockcroft-Gault equation; a single repeat test is allowed during the screening period to verify a result, with the exception of HIV tests. * Subjects with an ALT, alkaline phosphatase or bilirubin \>=1.5x Upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent). * The subject has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions.

Locations (3)

GSK Investigational Site

Hangzhou, Zhejiang, China

GSK Investigational Site

Beijing, China

GSK Investigational Site

Shanghai, China

Outcomes

Primary Outcomes

Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs): Injection Phase

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, or other situations as per investigator's judgement.

Time frame: Week 5 to 41

Number of Participants With Maximum Toxicity Post-Baseline in Hematology Parameters-Injection Phase

Hematology parameters were graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Higher grade indicates more severity. Clinical hematology parameters included: Activated partial thromboplastin time (APTT) prolonged, hemoglobin (Hb) (increased), white blood cells (WBC) (decreased), lymphocytes count (decreased), neutrophils (decreased), platelets (decreased), prothrombin international normalized ratio (Pro.INR) (increased). Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.

Time frame: Week 5 to 41

Number of Participants With Maximum Toxicity Post-Baseline in Chemistry Parameters: Injection Phase

Chemistry parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Higher grade indicates more severity. Clinical chemistry laboratory parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), Aspartate Aminotransferase (AST), bilirubin, calcium (hypercalcemia and hypocalcemia), carbon dioxide (CO2) (decreased), cholesterol (high), Creatine phosphokinase (CPK) increased, Creatinine increased, creatinine clearance (decreased), glucose (hyperglycemia and hypoglycemia), Hypophosphatemia, Potassium (Hyperkalemia and hypokalemia), Sodium (hypernatremia and hyponatremia), Hypertriglyceridemia, uric acid (increased). Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.

Time frame: Week 5 to 41

Number of Participants With Maximum Toxicity Post-Baseline in Urinalysis Parameters: Injection Phase

Urinalysis parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Urinalysis parameters included: Protein. Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.

Time frame: Week 5 to 41

Number of Participants With Shift From Baseline in Vital Signs With Respect to Clinical Concern Range: Injection Phase

Vital signs were measured after participants had rested in supine position for at least 5 minutes. Clinical concern ranges were: systolic blood pressure (SBP) (Low: \<85 millimeters of mercury \[mmHg\], High: \>160 mmHg), diastolic blood pressure (DBP) (Low: \<45 mmHg, High: \>100 mmHg), pulse rate (Low: \<40 mmHg, High: \>100 mmHg). Worst case results are presented. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%.

Time frame: Week 5 to 41

Number of Participants Withdrawn Due to AEs- Injection Phase

Time frame: Week 5 to 41

Number of Participants Experiencing Injection Site Reactions (ISR)-Injection Phase

Injection site reactions were recorded via ISR diaries and managed through investigator assessment. Number of participants who experienced any injection site reaction (like pain, itching, bruising, bump, discoloration, redness, skin firmness, swelling, warm to touch etc.) is presented.

Time frame: Week 5 to 41

Concentration of Cabotegravir in Plasma at the End of the Dosing Interval (Ctau)-Oral lead-in Phase

Blood samples were collected at the indicated time points for the determination of Ctau following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.