A Phase I, Open-label, Single Dose Escalation Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Two Different Formulations of Long-acting Cabotegravir Administered to Healthy Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- Cabotegravir Formulation F
- Conditions
- HIV Infections
- Sponsor
- ViiV Healthcare
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Plasma Concentration of cabotegravir at Week 4
- Status
- Completed
- Last Updated
- 2 months ago
Overview
Brief Summary
The primary purpose of the study is to investigate the safety, tolerability, and pharmacokinetic (PK) profiles of two different cabotegravir formulations in healthy adult participants. The study will initially start with the assessment of Cabotegravir Formulation F. Once the clinical batch of Cabotegravir Formulation G is available, this formulation will be assessed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
- •Body weight =\>40 kilogram (kg) and body mass index (BMI) within the range =\>18 to =\<32 kilogram per meter square (kg/m\^2)
- •Participants who are negative on a single test for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(approved molecular polymerase chain reaction \[PCR\] laboratory or point of care test) performed on the day of admission. A negative result is required prior to the administration of study intervention on Day
- •Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- •Participants assigned female at birth are eligible to participate if they are 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 \<1% from the time of screening and inclusive of the entire time while on the study.
- •A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within the 30 days before the first dose of study intervention.
- •Capable of giving written informed consent
Exclusion Criteria
- •Current presence or history of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, or neurological disorders.
- •Current or chronic history of liver disease or known hepatic or biliary abnormalities.
- •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.
- •Participants who in the investigator's judgment, poses a significant suicidality risk. Participant's history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
- •Positive SARS-CoV-2 polymerase chain reaction test, having signs and symptoms which in the opinion of the investigator are suggestive of COVID-19 (i.e., fever, cough etc) within 14 days of inpatient admission, or having contact with known COVID-19 positive person/s in the 14 days prior to inpatient admission.
- •Human immunodeficiency virus (HIV-1 or HIV-2) infection as indicated by positive antibody/antigen test.
- •History of or on-going high-risk behaviors that, in the opinion of the investigator, may put the participant at increased risk for HIV infection including, but not limited to, participants in HIV discordant relationships, or men who report current or prior unprotected anal sex with other men and those reporting prior or current injecting drug use.
- •Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
- •Abnormal blood pressure.
- •Evidence of previous myocardial infarction.
Arms & Interventions
Part A: Participants receiving Cabotegravir Formulation F
Intervention: Cabotegravir Formulation F
Part B: Participants receiving Cabotegravir Formulation G
Intervention: Cabotegravir Formulation G
Outcomes
Primary Outcomes
Plasma Concentration of cabotegravir at Week 4
Time Frame: Week 4
Absolute values of haematology parameters: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per litre)
Time Frame: Up to Week 52
Absolute value of haematology parameter: Red Blood Cell Count (RBC) (million cells per microliter)
Time Frame: Up to Week 52
Absolute values of haematology parameters: haemoglobin (Hgb) (grams per decilitre)
Time Frame: Up to Week 52
Absolute values of haematology parameters: Reticulocytes (Percentage of reticulocytes)
Time Frame: Up to Week 52
Absolute values of Clinical Chemistry parameters: Glucose (fasting), Blood Urea Nitrogen (BUN), Creatinine, Sodium, Potassium, Calcium, Direct Bilirubin and Total Bilirubin (milligrams per decilitre)
Time Frame: Up to Week 52
Absolute values of Clinical Chemistry parameters: AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per litre)
Time Frame: Up to Week 52
Clinical chemistry parameters such as Aspartate Aminotransferase (AST) / Serum Glutamic-Oxaloacetic Transaminase (SGOT), Alanine Aminotransferase (ALT)/ Serum Glutamic-Pyruvic Transaminase and (SGPT), Alkaline phosphatase (ALP) and Creatinine Phosphokinase (CPK) will be analysed.
Absolute value of haematology parameter: Mean Corpuscle Volume (MCV) (Femtoliters)
Time Frame: Up to Week 52
Change from Baseline in haematology parameter: Platelet count (cells per microliter)
Time Frame: Baseline (Day 1) and up to Week 52
Maximum observed plasma concentration (Cmax) of cabotegravir
Time Frame: Up to Week 52
Time of maximum observed plasma concentration (tmax) of cabotegravir
Time Frame: Up to Week 52
Number of participants with adverse events (AEs) based on severity
Time Frame: Up to Week 52
Absolute value of haematology parameter: Platelet count (cells per microliter)
Time Frame: Up to Week 52
Change from Baseline in haematology parameter: Red Blood Cell Count (RBC) (million cells per microliter)
Time Frame: Baseline (Day 1) and up to Week 52
Absolute values of haematology parameters: haematocrit (Proportion of red blood cells in blood)
Time Frame: Up to Week 52
Absolute values of Clinical chemistry parameters: Total Protein (Grams per deciliter)
Time Frame: Up to Week 52
Absolute values of Clinical chemistry parameters: Estimated Glomerular Filtration Rate (eGFR2) (millilitres per minute)
Time Frame: Up to Week 52
Change from baseline in Clinical Chemistry parameters: Glucose (fasting), Blood Urea Nitrogen (BUN), Creatinine, Sodium, Potassium, Calcium, Direct Bilirubin and Total Bilirubin (milligrams per decilitre)
Time Frame: Baseline (Day 1) and up to Week 52
Area under the concentration - time curve from time zero to 4 weeks following the injection (AUC[0-4]) of cabotegravir
Time Frame: Up to Week 4
Absolute value of haematology parameter: Mean Corpuscle haemoglobin (MCH) (Picograms)
Time Frame: Up to Week 52
Change from baseline in haematology parameter: Mean Corpuscle Volume (MCV) (Femtoliters)
Time Frame: Baseline (Day 1) and up to Week 52
Change from baseline in haematology parameters: Differential count of Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per litre)
Time Frame: Baseline (Day 1) and up to Week 52
Change from baseline in Clinical Chemistry parameters: AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per litre)
Time Frame: Baseline (Day 1) and up to Week 52
Clinical chemistry parameters such as Aspartate Aminotransferase (AST) / Serum Glutamic-Oxaloacetic Transaminase (SGOT), Alanine Aminotransferase (ALT)/ Serum Glutamic-Pyruvic Transaminase and (SGPT), Alkaline phosphatase (ALP) and Creatinine Phosphokinase (CPK) will be analysed
Change from baseline in haematology parameters: haematocrit (Proportion of red blood cells in blood)
Time Frame: Baseline (Day 1) and up to Week 52
Change from baseline in Clinical chemistry parameters: Estimated Glomerular Filtration Rate (eGFR) (millilitres per minute)
Time Frame: Baseline (Day 1) and up to Week 52
Change from baseline in haematology parameter: Mean Corpuscle haemoglobin (MCH) (Picograms)
Time Frame: Baseline (Day 1) and up to Week 52
Change from baseline in haematology parameters: Reticulocytes (Percentage of reticulocytes)
Time Frame: Baseline (Day 1) and up to Week 52
Change from baseline in Clinical chemistry parameters: Total Protein (Grams per deciliter)
Time Frame: Baseline (Day 1) and up to Week 52
Secondary Outcomes
- Plasma Concentration of cabotegravir at Week 8,12 and 24(Week 8, 12 and 24)
- Apparent terminal phase half-life (t1/2) of cabotegravir(Up to Week 52)
- Apparent long-acting absorption rate constant (KA-LA) of cabotegravir(Up to Week 52)
- Area under the concentration - time curve from time zero to infinity (AUC[0-inf]) of cabotegravir(Up to Week 52)
- Number of participants with maximum post-baseline QTc values compared to baseline by category (to <=450 milliseconds (msec) or no change, to >450 msec to <=480 msec, to >480 msec to <=500 msec, and to >500 msec)(Up to Week 52)
- Number of participants with worst case post-baseline values relative to potential clinical importance criteria compared to baseline for diastolic blood pressure (DBP), systolic blood pressure (SBP) and pulse rate(Up to Week 52)
- Area under the concentration - time curve from time zero to time of last quantifiable concentration [AUC(0-last)] of cabotegravir(Up to Week 52)
- Dose proportionality of cabotegravir based on AUC(0-inf), AUC(0-last), Cmax, and plasma concentration (Unit of measure: Slope of log dose)(Up to Week 52)
- Number of participants with maximum post-baseline increase in QTc values compared to baseline based on category (increase <=30 msec, increase of 31-60 msec, and increase of >60 msec)(Up to Week 52)