DDI Study of Etravirine and GSK1265744

A Phase I, Open Label Crossover Study to Evaluate the Effect of Etravirine on GSK1265744 Pharmacokinetics in Healthy Adult Subjects

The primary objective of this study is to compare steady-state plasma PK, safety and tolerability of GSK1265744 with and without etravirine

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Infection, Human Immunodeficiency Virus
• Intervention / Treatment: Drug: GSK1265744

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 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 cardiac monitoring.
• Male or female between 18 and 50 years of age.
• A female subject is eligible to participate if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant).
• Male subjects must agree to use one of the contraception methods listed in the protocol.
• Body weight >=50 kg for men and >=45 kg for women and body mass index (BMI) within the range 18.5-31.0 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

• The subject has a positive pre-study drug/alcohol screen.
• 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).
• 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 GSK Medical Monitor, contraindicates their participation.
• 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.
• Has a history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
• Pregnant females as determined by positive serum or urine human chorionic gonadotrophin (hCG) test at screening or prior to dosing.
• Lactating females.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• 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.
• History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PCTA) or any clinically significant cardiac disease.
• History/evidence of clinically significant pulmonary disease.
• History of significant renal or hepatic diseases.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• A positive test for HIV antibody.
• Serum creatinine values greater than the upper limit of normal. Serum ALT, ,AST, alkaline phosphatase or bilirubin > 1.5x upper limit of normal.
• 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 90-140mmHg, 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.
• Exclusion criteria for screening ECG

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; All subjects	Drug: GSK1265744; GSK drug; Other Names: etravirine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PK parameters of GSK1265744	24 days

Secondary Outcome Measures

Outcome Measure	Time Frame
PK parameters of etravirine	24 days
clinical laboratory assessmetns, vital signs, ECGs	24 days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: June 12, 2009
• First Submitted That Met QC Criteria: June 12, 2009
• First Posted (Estimate): June 15, 2009

Study Record Updates

• Last Update Posted (Estimate): August 31, 2010
• Last Update Submitted That Met QC Criteria: August 30, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: drug interaction; integrase inhibitor
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Etravirine; Cabotegravir
• Other Study ID Numbers: 111839