Healthy Volunteer Study To Assess The Bioavailability of GSK1265744 When Administered Orally Either When Fasted or Following a Meal.

A Single Dose, Randomized Study to Assess the Relative Bioavailability of Two Formulations and Food Effect on GSK1265744 in Healthy Male and Female Subjects

To evaluate the single dose relative bioavailability of GSK1265744 10mg administered in either oral solution fasted, two 5mg tablets fasted, or two 5mg tablets following a moderate meal.

Study Overview

• Status: Completed
• Conditions: HIV Infection; Infection, Human Immunodeficiency Virus
• Intervention / Treatment: Drug: GSK1265744 10 mg oral solution; Drug: GSK1265744 5 mg tablet; Drug: GSK1265744 5 mg tablet

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14202
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECG. 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 55 years of age.

• 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. A follicle stimulating hormone (FSH) level will be performed to confirm a post-menopausal status. For this study, FSH levels > 40 mlU/ml is confirmatory.
• A male is eligible to enter and participate in the study if he is surgically sterile OR if he either agrees to abstain from sexual intercourse with a female partner or agrees to use a condom/spermicide, in addition to having his female partner use another form of contraception as outlined in Section 7.1.
• Body weight >= 50 kg (110 lbs.) for men and >= 45 kg (99 lbs) for women and body mass index (BMI) within the range 18.5-31.0 kg/m2 (inclusive).
• A signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening.
• Subject must be 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.
• Has a positive pre-study Hepatitis B surface antigen; positive hepatitis C (HCV) antibody or detectable HCV ribonucleic acid (RNA); or positive HIV-1 antibody result.
• Has a history of regular alcohol consumption averaging >7 drinks/week for women or >14 drinks/week for men within 6 months of the screening visit.

Note: 1 drink is equivalent to 12 g alcohol = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.

• 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.
• Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated restrictions while participating in the study.
• The subject has received an investigational drug or participated in any other research trial within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
• Participation in the study would result in donation of blood in excess of 500 mL within a 56 day period.

Note: This does not include plasma donation.

- History or presence of allergy or intolerance to the study drug or its components or drugs of its class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.

Note: "Study" or "investigational" drugs include GSK1265744 or placebo.

• 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.
• Exclusion criteria for screening ECG per protocol
• The subject's systolic blood pressure is outside the range of 90-140mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 50-100bpm for female subjects or 45-100 bpm for male subjects.
• Has a history of regular use of tobacco- or nicotine-containing products within 3 months of the screening visit.
• The subject has a positive pre-study drug and/or alcohol screen.
• Use of prescription or non-prescription drugs, including antacids, vitamins, herbal and dietary supplements (including St John's Wort and iron supplements) 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 sponsor the medication will not interfere with the study procedures or compromise subject safety

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment A; GSK1265744 10mg oral solution	Drug: GSK1265744 10 mg oral solution; GSK1265744; Other Names: GSK1265744
EXPERIMENTAL: Treatment B; GSK1265744 5mg tablet, fasted	Drug: GSK1265744 5 mg tablet; GSK1265744 5mg tablet, fasted; Other Names: GSK1265744; Drug: GSK1265744 5 mg tablet; GSK1265744 5mg tablet, fed; Other Names: GSK1265744
EXPERIMENTAL: Treatment C; GSK1265744 5mg tablet, fed	Drug: GSK1265744 5 mg tablet; GSK1265744 5mg tablet, fasted; Other Names: GSK1265744; Drug: GSK1265744 5 mg tablet; GSK1265744 5mg tablet, fed; Other Names: GSK1265744

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of pharmacokinetic parameters	Plasma GSK1265744 Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC(0-infinity)], Area under the concentration-time curve over the dosing interval [AUC(0-t)], and Maximum observed concentration (Cmax).	6 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability parameters, including the collection adverse events		6 days
Composite of pharmacokinetic parameters	Plasma GSK1265744 Terminal phase half-life (t½), Lag time before observation of drug concentrations in sampled matrix (tlag), Time of occurrence of Cmax (tmax), and Apparent clearance following oral dosing (CL/F).	6 days
Safety and tolerability parameters including the change from baseline in clinical laboratory assessments	Clinical chemistry, hematology and urinalysis compared to baseline values	6 days
Safety and tolerability parameters including the collection of concurrent medication		6 days
Safety and tolerability parameters including the change from baseline in electrocardiogram values (ECG).		6 days
Safety and tolerability parameters including change from baseline in vital sign measurements	blood pressure and heart rate	6 days

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: GlaxoSmithKline; Shionogi

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): August 1, 2008
• Study Completion (ACTUAL): August 1, 2008

Study Registration Dates

• First Submitted: September 5, 2008
• First Submitted That Met QC Criteria: December 18, 2008
• First Posted (ESTIMATE): December 22, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): April 2, 2012
• Last Update Submitted That Met QC Criteria: March 29, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Healthy volunteer; HIV infected subjects; GSK1265744.
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Cabotegravir
• Other Study ID Numbers: ITZ111682