A Phase I Study Evaluating the Effect of a High Fat Meal on the Pharmacokinetics of Cabotegravir in Healthy Adult Volunteers
A Phase I Study Evaluating the Effect of a High Fat Meal on the Pharmacokinetics of Cabotegravir in Healthy Adult Volunteers
Cabotegravir is being developed for the treatment of human immunodeficiency virus (HIV) 1 infection. Specifically, it is being developed as a component of a 2-drug maintenance regimen (post-induction of viral suppression) that includes rilpivirine. Rilpivirine requires food for optimal absorption; therefore the recommended intake of cabotegravir in the planned Phase 3 treatment studies is with food regardless of fat or calorie content, when administered along with rilpivirine. This is a single-center, randomized, open-label, two-way crossover study in healthy adult subjects to assess the effect of a high fat meal on the single dose pharmacokinetics of CAB 30 mg. Approximately, 24 subjects will be enrolled in the study and will be screened for 30 days. Twelve subjects with at least 10 hours of fasting will be randomized to receive a single dose of cabotegravir orally (Schedule 'A'). The remaining 12 subjects will receive a single dose of cabotegravir orally along with high fat meal (Schedule 'B'). After 15 days, the subjects earlier undergoing 'Schedule A' will be switched to 'Schedule B' and those undergoing 'Schedule B' will undergo 'Schedule A'. All the subjects will be followed up to 30 days from the day of receiving first dose of cabotegravir to evaluate the effect of a high fat meal on the pharmacokinetics of cabotegravir.
Inclusion Criteria:
An eligible subject should be between 18 to 65 years of age inclusive, at the time of signing the informed consent
Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the medical monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Body weight >= 50 kilograms (kg) and body mass index (BMI) within the range 18.5 to 31.0 kilograms per squared meter (kg/m^2) (inclusive).
Male or female subjects. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies:
Non reproductive potential defined as:
Pre menopausal females with one of the following:
Reproductive potential and agrees to follow one of the options listed in the modified list of highly effective methods for avoiding pregnancy in females of reproductive potential (FRP) from 30 days prior to the first dose of the study medication and until after the last dose of the study medication and completion of the follow up visit. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception
Capable of giving signed informed consent that includes compliance with the requirements and restrictions listed in the consent form and in the protocol
Alanine aminotransferase (ALT), alkaline phosphatase, and bilirubin <=1.5x Upper Limit of Normal (ULN ) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
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 clinically significant cardiovascular disease including:
History of inflammatory bowel disease
History of cholecystectomy or other gastrointestinal surgery (except appendectomy more than three months prior to study)
History of peptic ulceration or pancreatitis within the preceding 6 months of screening
History of ongoing or clinically relevant seizure disorder within the previous 2 years, including subjects who have required treatment for seizures within this time period. A prior history of seizure, with a seizure free period of at least 2 years, off antiepileptics, 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 other medical condition which, in the judgment of the investigator and medical monitor, could jeopardize the integrity of the data derived from that subject or the safety of the subject. This includes but is not limited to any pre existing condition that interferes with normal gastrointestinal anatomy or motility that could interfere with the absorption, metabolism, and/or excretion of the study drug.
Unable to refrain from the use of prescription or non prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the investigator and GSK medical monitor the medication will not interfere with the study procedures or compromise subject safety.
History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams of alcohol: 12 ounces (360 milliliters (mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits
Urinary cotinine levels indicative of smoking or history or regular use of tobacco or nicotine containing products within 30 days prior to screening.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
Positive hepatitis B surface antigen (HBsAg), or a positive hepatitis B core antibody (HBcAb) with a negative hepatitis B surface antibody (HBsAb) at screening or within 3 months prior to first dose of study treatment.
Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of the study treatment.
A positive pre study drug/alcohol screen.
A positive test for HIV antibody.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
The subject's systolic blood pressure is outside the range of 90 to 140 millimeters of mercury (mmHg), or diastolic blood pressure is outside the range of 45 to 90 mmHg
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half lives or twice the duration of the biological effect of the investigational product (whichever is longer); however, the subject should not be participating in another clinical trial at the time of screening, and by the time of first dosing should not be within the time periods listed above
Exposure to more than four new chemical entities within 12 months prior to the first dosing day