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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Cabotegravir (GSK1265744B ) is available as white to almost white, oval shaped, film coated tablet, of weight 515 mg. The tablet contains micronized cabotegravir, lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycolate, and magnesium stearate. Each tablet is equivalent to 30 mg cabotegravir and needs to be taken orally with 240 mL of water. Cabotegravir tablet will be administered to subjects either in fasting condition or following a high fat meal.
GSK Investigational Site
Overland Park, Kansas, United States
Area under the concentration time curve from time zero (pre dose) extrapolated to infinite time of cabotegravir
AUC (0 infinity\[inf\]) is defined as the area under cabotegravir plasma concentration time curve from time zero (pre dose) extrapolated to infinite time.
Time frame: Pre dose, 0.5 hour (h), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on Day(D) 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2
Area under the concentration time curve from time zero (pre dose) to last time of quantifiable concentration of cabotegravir
AUC (0-t) is defined as area under cabotegravir plasma concentration time curve from time zero (pre dose) to the last time of quantifiable concentration.
Time frame: Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2
Maximum observed plasma concentration of cabotegravir
Cmax is defined as the maximum observed plasma concentration of cabotegravir.
Time frame: Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2
Concentration of cabotegravir at 24 hours post dose (C24)
C24 is defined as the plasma concentration at 24 hours after administration of cabotegravir.
Time frame: Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2
Plasma terminal phase half life of cabotegravir
Terminal elimination half life (t1/2) is defined as the duration until observation of half of the maximum concentration of cabotegravir.
Time frame: Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2
Lag time before observation of cabotegravir concentration in sampled matrix
tlag is the observed time prior to the first quantifiable plasma concentration of cabotegravir
Time frame: Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2
Time of occurrence of maximum observed plasma concentration of cabotegravir
tmax is defined as the time of the maximum observed plasma concentration of cabotegravir.
Time frame: Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2
Percentage of area under the concentration time curve of cabotegravir from time zero extrapolated to infinite time obtained by extrapolation
AUC (0-inf) is defined as the area under cabotegravir plasma concentration time curve from time zero (pre dose) extrapolated to infinite time. %AUCex is percentage of AUC(0 inf) obtained by extrapolation.
Time frame: Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2
Time of last measurable concentration of cabotegravir
tlast is defined as the time of the last observed quantifiable concentration of cabotegravir.
Time frame: Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2
Apparent clearance of cabotegravir following oral dosing
Clearance of a drug is a measure of rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose of cabotegravir (apparent oral clearance, CL/F) is influenced by the fraction of dose absorbed.
Time frame: Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2
Apparent volume of distribution of cabotegravir
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution of cabotegravir after oral dose (Vz/F) is influenced by the fraction absorbed.
Time frame: Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2
Number of subjects with adverse events and serious adverse events
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated), temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose can result in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/ incapacity, is a congenital anomaly/ birth defect, or any other situation related to impaired liver function.
Time frame: Upto approx. 68 days
Number of subjects with severity type
Intensity of an AE is used to rate the severity of an event. The intensities can be mild (easily tolerated), moderate (sufficiently discomforting to interfere with normal activities), or severe (prevents normal activities); however, both AEs and SAEs can be assessed as severe.
Time frame: Upto approx. 68 days
Number of subjects on concurrent medications
The number of subjects starting any other medication along with cabotegravir will be analyzed.
Time frame: Upto approx. 68 days
Number of subjects with abrnormal hematological and biochemistry laboratory parameters
Subjects will be assessed for any abnormality in hematological parameters such as platelet count, red blood cells (RBC) count, hemoglobin, hematocrit, absolute white blood cell (WBC) count, reticulocyte count, RBC distribution width, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCVC), differential WBC count including neutrophils, lymphocytes, monocytes, eosinophils, basophils and any abnormality in clinical chemistry parameters such as blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, potassium, chloride, calcium, total carbon dioxide, creatine phosphokinase (CPK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), alkaline phosphatase, total and direct Bilirubin, total protein, albumin, and uric acid. Subjects will be asked to fast for at least 4 hours prior to laboratory assessments. A single repeat will be performed.
Time frame: Upto approx. 68 days
Number of subjects with abnormal electrocardiogram
Duplicate ECGs will be collected with the subject in a semi supine position having rested in this position for at least 10 minutes beforehand and will be collected at Baseline (Day 1) of Period 1; however, single ECGs will be performed at all other timepoints. ECGs will be performed using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate according to Fridericia's formula (QTcF) intervals.
Time frame: At Screening (D 30 to D1), pre dose, and 4h post dose on D1
Number of subjects with abnormal vital signs (body temperature, systolic and diastolic blood pressure, and pulse rate)
Vital signs will be measured in semi supine position after 10 minutes rest and will include temperature, systolic and diastolic blood pressure and pulse rate. Measurements that deviate substantially from previous readings will be repeated immediately. Two blood pressure (BP) and heart rate (HR) measurements will be taken at pre dose on Day 1. The mean value recorded at pre dose will be classified as Baseline. Single BP and HR will be obtained at all other timepoints during the study.
Time frame: Upto approx. 68 days
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