An Interaction Study to Assess Drug Levels in Fasting Healthy Adult Subjects

• Status: Completed
• Trial end date: 2009-04-01
• Target enrollment: 0
• Participant gender: All

Summary

To date, no study has investigated whether there is a drug interaction between the protease inhibitor fosamprenavir and the integrase inhibitor raltegravir. COL112775 is a randomized, open-label, 6-arm, 3-period, drug interaction study to assess steady-state plasma amprenavir (APV) and raltegravir (RTG) pharmacokinetics in 48 healthy, fasting, HIV-negative adults after administration of a 7-day regimen of RTG 400mg BID alone and after 14-day regimens of unboosted fosamprenavir (FPV) 1400mg twice daily (BID), FPV 700mg/RTV 100mg BID, or FPV 1400mg/ritonavir (RTV) 100mg once daily (QD) with and without concurrent RTG 400mg BID. Blood samples for drug concentration measurement will be collected over 12 hours at the end of each dosing period. Subjects will undergo a physical examination, complete blood count (CBC) with differential, HIV test, hepatitis B/C test, liver function test, renal function analysis, and lipid panel at screening, and all of these tests, except those for HIV and hepatitis B/C, will be repeated at follow-up post-study. Adverse events and adherence (by pill count and medication diary) will be assessed by the investigator/study personnel at the end of each dosing period

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Garden State Infectious Disease Associates, PA
• Collaborator: GlaxoSmithKline
• Treatments: Fosamprenavir; Raltegravir Potassium; Ritonavir

Criteria

Inclusion Criteria:

• Healthy subjects with no clinically significant abnormality identified by physician by evaluation of medical history, physical examination, clinical laboratory tests or vital signs.

• Between 18 and 64 years.

• A female subject is eligible to participate if she is neither pregnant nor lactating, and falls into one of the following categories:

• non-childbearing potential including females with documented (medical report verification) hysterectomy or bilateral oophorectomy, or post-menopausal females defined as being amenorrheic for greater than 1 year and having estradiol and follicle stimulating hormone (FSH) levels consistent with menopause.

• childbearing potential with a negative serum pregnancy test at screen and who agrees to use one of the following methods of contraception from screening or at least two weeks prior to the first dose (whichever is earlier) until the follow-up visit (any contraception method must be used consistently and correctly, i.e., in accordance with both the product label and the instructions of a physician).

• Agreement for complete abstinence from intercourse.

• Double barrier contraception (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide).

• Any intrauterine device (IUD) with published data showing that the expected failure rate is less than 1% per year (not all IUDs meet this criterion)

• Any other method with published data showing that the lowest expected failure rate for that method is less than 1% per year.

• Adequate renal function (calculated creatinine clearance via Cockcroft and Gault method (CrCl) > 50 mL/min).

• Adequate hepatic function (total bilirubin < 2.5mg/dL; hepatic transaminases < 5x normal).

• Adequate hematologic function (absolute neutrophil count [ANC] > 750 neutrophils/mm^3; platelets > 50,000/mm^3; hematocrit > 25%).

• Non-smoker, defined as not having used nicotine-containing products within the past 6 months.

• Willingness and ability to adhere to treatment and follow-up procedures.

• The ability to understand and sign a written informed consent form.

• Body weight > or =50 kg for males and > or=45 kg for females and body mass index (BMI) in the range of 19 to 30 kg/m^2 (BMI = weight [kg]/(height [m])^2).

Exclusion Criteria:

• Have an active infection that required parenteral antibiotics or hospitalization within 2 weeks prior to enrollment.

• A history of or documented gastrointestinal diseases that impact drug absorption.

• Have a significant documented sulfa allergy (e.g., Stevens-Johnson Syndrome) or a history of sensitivity to any of the study medications, or components thereof.

• HIV, Hepatitis B or C positive .

• Cigarette/cigar/pipe smokers.

• History of alcohol/drug abuse or dependence within 12 months of the study, or a history of alcohol consumption in the past six months exceeding 7 units/week for women and 14 units/week for men (where 1 unit = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor).

• Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.

• Use of prescription or non-prescription drugs (including aspirin and nonsteroidal anti-inflammatory drug (NSAIDs), vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer, such as St. John's Wort) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the investigator the medication will not interfere with the study procedures or compromise subject safety.

• Subjects who have donated plasma within 7 days prior to the screening visit or where participation in this study would result in donation of blood in excess of 500 mL of blood within 56 day period.