A Study to Assess the Food Effect and the Relative Bioavailability of the Cabotegravir (CAB) Pediatric Dispersible Tablet (DT) Formulation

Study Overview
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Brief Summary
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This study will assess the relative bioavailability of the CAB DT formulation relative to that of the CAB IR formulation and to assess the effect of food on the CAB DT formulation.

Official Title
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A Phase 1, Single-center, Randomized, Open-label, Single Dose, Three-period, Balanced Crossover Study to Assess the Effect of Food on the Pediatric Dispersible Tablet Formulation of Cabotegravir and to Assess the Relative Bioavailability Between the Pediatric Dispersible Tablet (DT) Formulation and Immediate Release (IR) Tablet Formulation of Cabotegravir in Healthy Adult Participants

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Cabotegravir IR Formulation (reference)
* Drug: Cabotegravir DT Formulation (test 1)
* Drug: Cabotegravir DT Formulation (test 2)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent form (ICF). Participants who are healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and electrocardiogram). Body weight greater than or equal to (>=) 50.0 kilograms (kg) (110 pounds [lbs]) for males and >= 45 kg (99 lbs) for females and Body mass index within the range 18.5 to 31.0 kilogram per meter square (kg/m2) (inclusive) at Screening. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Female: A female participant is eligible to participate if she is not pregnant or breastfeeding and is a Women of non child bearing potential (WONCBP) OR Is a Women of child bearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of less than (<)1 percent (%) per year). A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention (i.e., Day-1 of each treatment Period) 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. Exclusion Criteria: History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, 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. History of seizures, and participants are required to have been seizure free, off anti epileptic drugs for a minimum of 2 years and will only be considered for enrollment following discussion with the Medical Monitor Abnormal blood pressure as determined by the investigator. Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3 months, or cardiac disease or a family or personal history of long QT syndrome. A pre-existing condition interfering with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study intervention. Known suspected active Coronavirus disease 2019 (COVID-19) infection OR contact with an individual with known COVID-19 , within 14 days of study enrollment Any acute laboratory abnormality at screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound. Any Grade 2 to 4 laboratory abnormality at screening, with Creatine Phosphokinase and lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT abnormalities, will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A positive test result for drugs of abuse (including marijuana), alcohol, or tobacco (indicating active current smoking) at screening or before the first dose of study intervention. Unable to refrain from the use of prescription or non-prescription drugs as detailed in the protocol. Unwillingness to abstain from excessive consumption of any food or drink detailed in the protocol. Would not be able to accommodate the blood loss during participation in the study Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day. Current enrollment or past participation in another investigational study as detailed in the protocol. Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing. - Current enrollment or past participation in this clinical study. Positive hepatitis B and/or C test result at screening or within 3 months prior to first dose of study intervention. Positive pre-study drug/alcohol screen, including Tetrahydrocannabinol Positive Human immunodeficiency virus (HIV) antibody test (4th generation assay required). Regular use of tobacco- or nicotine-containing products within 6 months prior to screening History of regular alcohol consumption within 6 months of the study, History of sensitivity, prior intolerance or hypersensitivity to any of the study interventions, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation. Participant and/or his her family is part of sponsor, clinical site, third party personnel.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAB IR Formulation (reference)/CAB DT Formulation (Test 1)/CAB DT Formulation (Test 2)<br>Participants will receive CAB IR Formulation (reference) under fasted conditions in treatment period 1 followed by CAB DT Formulation (test 1) under fasted conditions in treatment period 2 followed by CAB DT Formulation (test 2) under fed conditions in treatment period 3. There will be a minimum washout period of 14 days between each treatment . | Drug: Cabotegravir IR Formulation (reference)<br>* Cabotegravir IR Formulation (reference) will be administered.<br>Drug: Cabotegravir DT Formulation (test 1)<br>* Cabotegravir DT Formulation (test 1) will be administered.<br>Drug: Cabotegravir DT Formulation (test 2)<br>* Cabotegravir DT Formulation (test 2) will be administered.<br>|
| Experimental: CAB DT Formulation (Test 1)/CAB IR Formulation (reference)/CAB DT Formulation (test 2)<br>Participants will receive CAB DT Formulation (test 1) under fasted conditions in treatment period 1 followed by CAB IR Formulation (reference) under fasted conditions in treatment period 2 followed by CAB DT Formulation (test 2) under fed conditions in treatment period 3. There will be a minimum washout period of 14 days between each treatment. | Drug: Cabotegravir IR Formulation (reference)<br>* Cabotegravir IR Formulation (reference) will be administered.<br>Drug: Cabotegravir DT Formulation (test 1)<br>* Cabotegravir DT Formulation (test 1) will be administered.<br>Drug: Cabotegravir DT Formulation (test 2)<br>* Cabotegravir DT Formulation (test 2) will be administered.<br>|
| Experimental: CAB DT Formulation (test 2)/CAB IR Formulation (reference)/CAB DT Formulation (test 1)<br>Participants will receive CAB DT Formulation (test 2) under fed conditions in treatment period 1 followed by CAB IR Formulation (reference) under fasted conditions in treatment period 2 followed by CAB DT Formulation (test 1) under fasted conditions in treatment period 3. There will be a minimum washout period of 14 days between each treatment. | Drug: Cabotegravir IR Formulation (reference)<br>* Cabotegravir IR Formulation (reference) will be administered.<br>Drug: Cabotegravir DT Formulation (test 1)<br>* Cabotegravir DT Formulation (test 1) will be administered.<br>Drug: Cabotegravir DT Formulation (test 2)<br>* Cabotegravir DT Formulation (test 2) will be administered.<br>|
| Experimental: CAB IR Formulation (reference)/CAB DT Formulation (test 2)/CAB DT Formulation (test 1)<br>Participants will receive CAB IR Formulation (reference) under fasted conditions in treatment period 1 followed by CAB DT Formulation (test 2) under fed conditions in treatment period 2 followed by CAB DT Formulation (test 1) under fasted conditions in treatment period 3. There will be a minimum washout period of 14 days between each treatment. | Drug: Cabotegravir IR Formulation (reference)<br>* Cabotegravir IR Formulation (reference) will be administered.<br>Drug: Cabotegravir DT Formulation (test 1)<br>* Cabotegravir DT Formulation (test 1) will be administered.<br>Drug: Cabotegravir DT Formulation (test 2)<br>* Cabotegravir DT Formulation (test 2) will be administered.<br>|
| Experimental: CAB DT Formulation (test 1)/CAB DT Formulation (test 2)/CAB IR Formulation (reference)<br>Participants will receive CAB DT Formulation (test 1) under fasted conditions in treatment period 1 followed by CAB DT Formulation (test 2) under fed conditions in treatment period 2 followed by CAB IR Formulation (reference) under fasted conditions in treatment period 3. There will be a minimum washout period of 14 days between each treatment. | Drug: Cabotegravir IR Formulation (reference)<br>* Cabotegravir IR Formulation (reference) will be administered.<br>Drug: Cabotegravir DT Formulation (test 1)<br>* Cabotegravir DT Formulation (test 1) will be administered.<br>Drug: Cabotegravir DT Formulation (test 2)<br>* Cabotegravir DT Formulation (test 2) will be administered.<br>|
| Experimental: CAB DT Formulation (test 2)/CAB DT Formulation (test 1)/CAB IR Formulation (reference)<br>Participants will receive CAB DT Formulation (test 2) under fed conditions in treatment period 1 followed by CAB DT Formulation (test 1) under fasted conditions in treatment period 2 followed by CAB IR Formulation (reference) under fasted conditions in treatment period 3. There will be a minimum washout period of 14 days between each treatment. | Drug: Cabotegravir IR Formulation (reference)<br>* Cabotegravir IR Formulation (reference) will be administered.<br>Drug: Cabotegravir DT Formulation (test 1)<br>* Cabotegravir DT Formulation (test 1) will be administered.<br>Drug: Cabotegravir DT Formulation (test 2)<br>* Cabotegravir DT Formulation (test 2) will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) following administration of CAB DT after a high fat meal |  | Up to 168 hours | 
| Area under the concentration time curve from time zero (pre-dose) extrapolated to last time of quantifiable concentration (AUC[0-last]) following administration of CAB DT after a high fat meal |  | Up to 168 hours | 
| Maximum observed concentration (Cmax) following administration of CAB DT after a high fat meal |  | Up to 168 hours | 
| AUC(0-inf) following administration of CAB DT in fasted state |  | Up to 168 hours | 
| AUC(0-last) following administration of CAB DT in fasted state |  | Up to 168 hours | 
| Cmax following administration of CAB DT in fasted state |  | Up to 168 hours | 
| AUC(0-inf) following administration of CAB IR in fasted state |  | Up to 168 hours | 
| AUC(0-last) following administration of CAB IR in fasted state |  | Up to 168 hours | 
| Cmax following administration of CAB IR in fasted state |  | Up to 168 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent terminal phase half-life (T1/2) following administration of CAB DT |  | Up to 168 hours | 
| Lag time before observation of drug concentrations in sampled matrix (tlag) following administration of CAB DT |  | Up to 168 hours | 
| Time of occurrence of Cmax (Tmax) following administration of CAB DT |  | Up to 168 hours | 
| Area under the concentration time curve from time zero extrapolated to 72 hours post-dose AUC(0-72) following administration of CAB DT |  | Up to 72 Hours | 
| Concentration at 24 hours post-dose (C24) of following administration of CAB DT |  | At 24 Hours | 
| Apparent oral clearance (CL/F) following administration of CAB DT |  | Up to 168 hours | 
| Apparent volume of distribution (Vz/F) following administration of CAB DT |  | Up to 168 hours | 
| T1/2 following administration of CAB DT in fasted state |  | Up to 168 hours | 
| Tlag following administration of CAB DT in fasted state |  | Up to 168 hours | 
| Tmax following administration of CAB DT in fasted state |  | Up to 168 hours | 
| AUC(0-72) following administration of CAB DT in fasted state |  | Up to 72 Hours | 
| C24 following administration of CAB DT in fasted state |  | At 24 Hours | 
| CL/F following administration of CAB DT in fasted state |  | Up to 168 hours | 
| Vz/F following administration of CAB DT in fasted state |  | Up to 168 hours | 
| T1/2 following administration of CAB IR in fasted state |  | Up to 168 hours | 
| Tlag following administration of CAB IR in fasted state |  | Up to 168 hours | 
| Tmax following administration of CAB IR in fasted state |  | Up to 168 hours | 
| AUC(0-72) following administration of CAB IR in fasted state |  | Up to 72 Hours | 
| C24 following administration of CAB IR in fasted state |  | Up to 168 hours | 
| CL/F following administration of CAB IR in fasted state |  | Up to 168 hours | 
| Vz/F following administration of CAB IR in fasted state |  | Up to 168 hours | 
| Number of participants with Non-Serious Adverse events (AEs) and Serious adverse events (SAEs) |  | Up to 6 Weeks | 
| Number of participants with AEs by severity |  | Up to 6 Weeks | 
| Change from Baseline in Vital sign parameter: Oral Temperature (Degrees Celsius) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in Vital sign parameter: Pulse rate (Beats per minute) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in Vital sign parameter: Respiratory rate (Breaths per minute) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in Vital sign parameter: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (Millimeters of mercury) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in Electrocardiogram (ECG) parameters: PR Interval, QRS Interval, QT Interval, Corrected QT interval using the Fridericia formula (QTcF) (Milliseconds) |  | Baseline and Up to 6 Weeks | 
| Number of participants with maximum toxicity grade increase from Baseline in hematology, chemistry and urinalysis parameters |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet Count (Giga cells per Liter) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in hematology parameter: Red Blood Cell Count (Trillion cells per liter) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in hematology parameter: Hemoglobin (Grams per liter) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in hematology parameter: Hematocrit (Proportion of red blood cells in blood) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in hematology parameter: Mean Corpuscular Volume (Femtoliters) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in hematology parameter: Mean Corpuscular Hemoglobin (Picograms) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in hematology parameter: Percentage of Reticulocytes (Percentage of reticulocytes) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in chemistry parameters: Creatinine, Total and Direct Bilirubin (Micromoles per liter) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in chemistry parameters: Calcium, Glucose, Potassium, Sodium, Blood urea nitrogen, Carbon dioxide (Millimoles per liter) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in chemistry parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Creatine phosphokinase (International units per liter) |  | Baseline and Up to 6 Weeks | 
| Change from Baseline in chemistry parameters: Total Protein (Grams per liter) |  | Baseline and Up to 6 Weeks | 
| Number of participants with abnormal urinalysis parameters |  | Up to 6 Weeks | 
| Absolute values of hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet Count (Giga cells per Liter) |  | Up to 6 Weeks | 
| Absolute values of hematology parameter: Red Blood Cell Count (Trillion cells per liter) |  | Up to 6 Weeks | 
| Absolute values of hematology parameter: Hemoglobin (Grams per liter) |  | Up to 6 Weeks | 
| Absolute values of hematology parameter: Hematocrit (Proportion of red blood cells in blood |  | Up to 6 Weeks | 
| Absolute values of hematology parameter: Mean Corpuscular Volume (Femtoliters) |  | Up to 6 Weeks | 
| Absolute values of hematology parameter: Mean Corpuscular Hemoglobin (Picograms) |  | Up to 6 Weeks | 
| Absolute values of hematology parameter: Percentage of Reticulocytes (Percentage of reticulocytes) |  | Up to 6 Weeks | 
| Absolute values of chemistry parameters: Creatinine, Total and Direct Bilirubin (Micromoles per liter) |  | Up to 6 Weeks | 
| Absolute values of chemistry parameters: Calcium, Glucose, Potassium, Sodium, Blood urea nitrogen, Carbon dioxide (Millimoles per liter) |  | Up to 6 Weeks | 
| Absolute values of chemistry parameters: ALT, ALP, AST and Creatine phosphokinase (International units per liter) |  | Up to 6 Weeks | 
| Absolute values of chemistry parameters: Total Protein (Grams per liter) |  | Up to 6 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dispersible tablet, Bioavailability, Cabotegravir, Food effect, Human immunodeficiency virus, Immediate release tablet