A Phase I, Open Label, Two Period, Single Fixed-Sequence Crossover Study to Evaluate the Effect of Etravirine on GSK1349572 Pharmacokinetics in Healthy Adult Subjects (ING111603)

GSK1349572 Drug Interaction Study With Etravirine

Sponsors

Lead sponsor: GlaxoSmithKline

Collaborator: Shionogi

Source GlaxoSmithKline
Brief Summary

A study in healthy volunteers to determine whether there is a drug interaction between GSK1349572 and etravirine

Overall Status Completed
Start Date October 2008
Completion Date December 2008
Primary Completion Date December 2008
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, Ctau, and Cmin following administration of GSK1349572 50 mg q24h for 5 days and following co-administration with ETV 200 mg q12h for 14 days. 19 days
Secondary Outcome
Measure Time Frame
Safety and tolerability parameters, including adverse event, concurrent medication, clinical laboratory, ECG, and vital signs assessments. 19 days
Plasma ETV steady state PK parameters, including AUC(0-t), t½, Cmax, and Cmin following co-administration of GSK1349572 50 mg q24h and ETV 200 mg q12h. 19 days
Enrollment 16
Condition
Intervention

Intervention type: Drug

Intervention name: GSK1349572

Description: GSK1349572 50 mg in combination with Etravirine

Arm group label: Sequence 1

Eligibility

Criteria:

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 65 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. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt, HRT should be discontinued for 2 weeks and then the subject rescreened, as HRT can suppress FSH.

- Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 14 days after the last dose of study medication.

- 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. 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, 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.

- 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. One 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.

- 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 or AST > 2x upper limit of normal.A single repeat is allowed for eligibility determination.

- 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.

- ECG criteria outside protocol limits.

Gender: All

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
GSK Clinical Trials Study Director GlaxoSmithKline
Location
facility GSK Investigational Site
Location Countries

United States

Verification Date

May 2009

Responsible Party

Name title: Study Director

Organization: GSK

Keywords
Has Expanded Access No
Number Of Arms 1
Arm Group

Arm group label: Sequence 1

Arm group type: Experimental

Study Design Info

Allocation: Non-Randomized

Intervention model: Single Group Assignment

Masking: None (Open Label)

Source: ClinicalTrials.gov