Phase 1, Open Label, Two Arm, Fixed Sequence Study to Evaluate the Effect of Rifampin and Rifabutin on GSK1349572 Pharmacokinetics in Healthy Male and Female Volunteers

ViiV Healthcare1 site in 1 country27 target enrollmentMay 2011

Overview

Brief Summary

This study will be a phase I, open label, two arm, fixed sequence crossover study to investigate the effect of rifampin and rifabutin on the steady state pharmacokinetics (PK) of GSK1349572 and the safety and tolerability of GSK1349572 and rifamycin co-administration. Subjects enrolled in Arm 1 will receive GSK1349572 50 mg once daily for 7 days, GSK1348572 50 mg twice daily for 7 days, and GSK1349572 50 mg twice daily in combination with rifampin 600 mg once daily for 14 days. Subjects in Arm 2 will receive GSK1349572 50 mg once daily for 7 days and GSK1349572 50 mg once daily in combination with rifabutin 300 mg once daily for 14 days. Serial PK sampling will be completed following the last dose of each treatment. Safety and tolerability will be assessed throughout the study through assessment of adverse events (AEs), and clinical laboratory tests.

This study will be conducted at one center in the US with healthy adult male and female subjects.

Registry

clinicaltrials.gov

Start Date

May 2011

End Date

December 2011

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

ViiV Healthcare

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and electrocardiogram (ECG).
•Within 28 or fewer days prior to enrollment, a complete blood count with differential, comprehensive serum chemistry profile, human immunodeficiency virus (HIV) antibody test, and Hepatitis C antibody test will be performed, with the following laboratory values:
•Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin less than or equal to upper limit of normal (ULN)
•Hemoglobin greater than or equal to 12.0 for men, greater than or equal to11.0 for women
•Serum creatinine less than or equal to1.5 mg/dL
•Platelet count greater than or equal to 125,000 /cu mm
•Absolute neutrophil count greater than or equal to 1250 /cu mm
•HIV antibody test negative
•Hepatitis C antibody negative
•Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.

Exclusion Criteria

•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.
•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 or 5 half-lives (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.
•If heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
•History of regular alcohol consumption within 6 months of the study defined as:
•An average weekly intake of \>14 drinks/week for men or \>7 drinks/week for women.
•Any illicit drug use within the preceding 2 months.
•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.

Arms & Interventions

Arm 1

Subjects will have a screening visit within 30 days prior to the first dose of study drug, three treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. Subjects enrolled in Arm 1 will receive GSK1349572 50 mg once daily for 7 days, GSK1348572 50 mg twice daily for 7 days, and GSK1349572 50 mg twice daily in combination with rifampin 600 mg once daily for 14 days.

Intervention: GSK1349572

Arm 1

Subjects will have a screening visit within 30 days prior to the first dose of study drug, three treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. Subjects enrolled in Arm 1 will receive GSK1349572 50 mg once daily for 7 days, GSK1348572 50 mg twice daily for 7 days, and GSK1349572 50 mg twice daily in combination with rifampin 600 mg once daily for 14 days.

Intervention: Rifampin

Arm 2

Subjects will have a screening visit within 30 days prior to the first dose of study drug, two treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. Subjects in Arm 2 will receive GSK1349572 50 mg once daily for 7 days and GSK1349572 50 mg once daily in combination with rifabutin 300 mg once daily for 14 days.

Intervention: GSK1349572

Arm 2

Subjects will have a screening visit within 30 days prior to the first dose of study drug, two treatment periods, and a follow-up visit 7-14 days after the last dose of study drug. Subjects in Arm 2 will receive GSK1349572 50 mg once daily for 7 days and GSK1349572 50 mg once daily in combination with rifabutin 300 mg once daily for 14 days.

Intervention: Rifabutin