A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Two Different Formulations of Long-acting Cabotegravir in Healthy Adult Participants

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06033547
• Other study ID #: 219406
• Status: Recruiting
• Phase: Phase 1
• Start date: September 12, 2023
• Est. completion date: July 24, 2025

Study information

• Verified date: April 2024
• Source: ViiV Healthcare
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: July 24, 2025
• Est. primary completion date: July 24, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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 1.

• 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.

• Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular [AV] block [2nd degree or higher], Wolff- Parkinson-White [WPW] syndrome).

• Any significant arrhythmia which, in the opinion of the investigator or the medical monitor, will interfere with the safety for the individual participant.

• One or more exclusionary values for a screening Electrocardiogram (ECG).

• Alanine transaminase (ALT) >1.5x upper limit of normal (ULN).

• Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]).

• Estimated Glomerular Filtration Rate (eGFR) <60 milliliter per minute (mL/min) using the Chronic Kidney Disease - Improved Prediction Equations (CKD-EPI) Creatinine Equation (2021).

• Haemoglobin <12.5 gram per deciliter (g/dL) for men and <11 g/dL for women.

• Positive pre-study drug/alcohol screen.

• Regular use of tobacco- or nicotine-containing products within 3 months prior to screening; or urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g., nicotine patches or vaporizing devices).

• 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.

• Concurrent participation in another clinical trial (except imaging trials); or has participated in a clinical trial and received an investigational product within the following time period prior to the first dosing day in this study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

• 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 four (4) new chemical entities within 12 months prior to the first dosing day.

• History of sensitivity to any of the study interventions (or components thereof), a history of drug allergy or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation

• Current or anticipated need for chronic anti-coagulation therapy (with the exception of low-dose aspirin =< 325 mg/day)

• Hereditary coagulation and platelet disorders (e.g., haemophilia or Von Willebrand disease [VWD]).

• Participant has a tattoo overlying the location of injection or an underlying skin disease or condition (e.g., infection, inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria) that, in the opinion of the investigator, may interfere with interpretation of injection site reactions or administration of study intervention.

• 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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Cabotegravir Formulation F
Cabotegravir Formulation F will be administered
• Cabotegravir Formulation G
Cabotegravir Formulation G will be administered

Locations

Country	Name	City	State
United States	GSK Investigational Site	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
ViiV Healthcare

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed plasma concentration (Cmax) of cabotegravir		Up to Week 52
Primary	Time of maximum observed plasma concentration (tmax) of cabotegravir		Up to Week 52
Primary	Area under the concentration - time curve from time zero to 4 weeks following the injection (AUC[0-4]) of cabotegravir		Up to Week 4
Primary	Plasma Concentration of cabotegravir at Week 4		Week 4
Primary	Number of participants with adverse events (AEs) based on severity		Up to Week 52
Primary	Absolute value of haematology parameter: Platelet count (cells per microliter)		Up to Week 52
Primary	Absolute value of haematology parameter: Red Blood Cell Count (RBC) (million cells per microliter)		Up to Week 52
Primary	Absolute values of haematology parameters: haemoglobin (Hgb) (grams per decilitre)		Up to Week 52
Primary	Absolute values of haematology parameters: haematocrit (Proportion of red blood cells in blood)		Up to Week 52
Primary	Absolute value of haematology parameter: Mean Corpuscle Volume (MCV) (Femtoliters)		Up to Week 52
Primary	Absolute value of haematology parameter: Mean Corpuscle haemoglobin (MCH) (Picograms)		Up to Week 52
Primary	Absolute values of haematology parameters: Reticulocytes (Percentage of reticulocytes)		Up to Week 52
Primary	Absolute values of haematology parameters: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per litre)		Up to Week 52
Primary	Absolute values of Clinical Chemistry parameters: Glucose (fasting), Blood Urea Nitrogen (BUN), Creatinine, Sodium, Potassium, Calcium, Direct Bilirubin and Total Bilirubin (milligrams per decilitre)		Up to Week 52
Primary	Absolute values of Clinical Chemistry parameters: AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per litre)	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.	Up to Week 52
Primary	Absolute values of Clinical chemistry parameters: Total Protein (Grams per deciliter)		Up to Week 52
Primary	Absolute values of Clinical chemistry parameters: Estimated Glomerular Filtration Rate (eGFR2) (millilitres per minute)		Up to Week 52
Primary	Change from Baseline in haematology parameter: Platelet count (cells per microliter)		Baseline (Day 1) and up to Week 52
Primary	Change from Baseline in haematology parameter: Red Blood Cell Count (RBC) (million cells per microliter)		Baseline (Day 1) and up to Week 52
Primary	Change from baseline in haematology parameters: haematocrit (Proportion of red blood cells in blood)		Baseline (Day 1) and up to Week 52
Primary	Change from baseline in haematology parameter: Mean Corpuscle Volume (MCV) (Femtoliters)		Baseline (Day 1) and up to Week 52
Primary	Change from baseline in haematology parameter: Mean Corpuscle haemoglobin (MCH) (Picograms)		Baseline (Day 1) and up to Week 52
Primary	Change from baseline in haematology parameters: Reticulocytes (Percentage of reticulocytes)		Baseline (Day 1) and up to Week 52
Primary	Change from baseline in haematology parameters: Differential count of Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per litre)		Baseline (Day 1) and up to Week 52
Primary	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)		Baseline (Day 1) and up to Week 52
Primary	Change from baseline in Clinical Chemistry parameters: AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per litre)	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	Baseline (Day 1) and up to Week 52
Primary	Change from baseline in Clinical chemistry parameters: Total Protein (Grams per deciliter)		Baseline (Day 1) and up to Week 52
Primary	Change from baseline in Clinical chemistry parameters: Estimated Glomerular Filtration Rate (eGFR) (millilitres per minute)		Baseline (Day 1) and up to Week 52
Secondary	Area under the concentration - time curve from time zero to infinity (AUC[0-inf]) of cabotegravir		Up to Week 52
Secondary	Area under the concentration - time curve from time zero to time of last quantifiable concentration [AUC(0-last)] of cabotegravir		Up to Week 52
Secondary	Plasma Concentration of cabotegravir at Week 8,12 and 24		Week 8, 12 and 24
Secondary	Apparent terminal phase half-life (t1/2) of cabotegravir		Up to Week 52
Secondary	Apparent long-acting absorption rate constant (KA-LA) of cabotegravir		Up to Week 52
Secondary	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
Secondary	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
Secondary	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
Secondary	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	Number of participants with worst case post-baseline values relative to potential clinical importance criteria compared to baseline will be categorized into change to low, change to within range or no change, and change to high	Up to Week 52