A Single-center, Randomized, Open-label, Crossover Study to Assess the Relative Bioavailability of Tablet Formulations of GSK2248761 in Healthy Adult Subjects. SGN114435
Overview
- Phase
- Phase 1
- Intervention
- GSK2248761 WBM Capsule
- Conditions
- Infections, Human Immunodeficiency Virus and Herpesviridae
- Sponsor
- ViiV Healthcare
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Plasma GSK2248761 Maximum observed concentration (Cmax)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This is a single-center, randomized, two part, open-label, crossover study in healthy adult subjects to assess the oral bioavailability of three GSK2248761 Wet Bead Milled (WBM) tablet formulations manufactured by three different processes relative to the GSK2248761 WBM capsule formulation (Part A) and the effect of a moderate-fat meal on the bioavailability of the selected WBM tablet formulation (Part B).
Detailed Description
ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ECGs. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- •Male or female between 18 and 50 years of age inclusive, at the time of signing the informed consent.
- •A female subject is eligible to participate if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who: Is pre-menopausal with a documented bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy, or Is post-menopausal defined as 12 months of spontaneous amenorrhea.
- •Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the follow-up visit.
- •Body weight greater than or equal to 50 kilograms (kg) for men and greater than or equal to 45 kg for women and body mass index (BMI) within the range 18.5-31.0 kilograms per meters squared (inclusive).
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Exclusion Criteria
- •As a result of the medical interview, physical examination, or screening investigations, the Investigator considers the subject unfit for the study.
- •The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- •Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
- •History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of greater than14 drinks/week for men or greater than 7 drinks/week for women.
- •Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until collection of the final pharmacokinetic sample during each treatment period.
- •History or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
- •History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting surgery or percutaneous transluminal coronary angioplasty or any clinically significant cardiac disease.
- •History/evidence of clinically significant pulmonary disease.
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy should be excluded.
Arms & Interventions
Periods 1 - 4
Subjects will be randomized in a cross over fashion to receive the GSK2248761 WBM capsule formulation or one of three WBM tablet formulations in one of four sequences.
Intervention: GSK2248761 WBM Capsule
Periods 1 - 4
Subjects will be randomized in a cross over fashion to receive the GSK2248761 WBM capsule formulation or one of three WBM tablet formulations in one of four sequences.
Intervention: GSK2248761 WBM Tablet Formulation 1
Periods 1 - 4
Subjects will be randomized in a cross over fashion to receive the GSK2248761 WBM capsule formulation or one of three WBM tablet formulations in one of four sequences.
Intervention: GSK2248761 WBM Tablet Formulation 2
Periods 1 - 4
Subjects will be randomized in a cross over fashion to receive the GSK2248761 WBM capsule formulation or one of three WBM tablet formulations in one of four sequences.
Intervention: GSK2248761 WBM Tablet Formulation 3
Period 5
Subjects in Part B will receive a formulation of GSK2248761 200mg WBM Tablet chosen from Periods 1 - 4 in part A in the fed state (moderate fat meal).
Intervention: GSK2248761 WBM Tablet
Outcomes
Primary Outcomes
Plasma GSK2248761 Maximum observed concentration (Cmax)
Time Frame: 5 weeks
Plasma GSK2248761 Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity))
Time Frame: 5 weeks
Plasma GSK2248761 observed concentration 24 hours after dose (C24)
Time Frame: 5 weeks
Plasma GSK2248761 Area under the concentration-time curve over the dosing interval (AUC (0 - t))
Time Frame: 5 weeks
Secondary Outcomes
- Clinical laboratory screens(5 weeks)
- Vital sign assessments (systolic and diastolic blood pressure and pulse)(5 weeks)
- Plasma GSK2248761 Time of occurrence of Cmax (tmax)(5 weeks)
- Plasma GSK2248761 Apparent clearance following oral dosing (CL/F)(5 weeks)
- Plasma GSK2248761 terminal phase half life (t½)(5 weeks)
- Plasma GSK2248761 Percentage of AUC(0-infinity) obtained by extrapolation (%AUCex)(5 weeks)
- Plasma GSK2248761 Time of last quantifiable concentration (tlast)(5 weeks)
- Safety and tolerability parameters, including adverse events(5 weeks)
- concurrent medication(5 weeks)
- Electrocardiograms (ECG)(5 weeks)
- Plasma GSK2248761 Lag time before observation of drug concentrations (tlag)(5 weeks)