An Interaction Study to Assess Drug Levels in Healthy Adult Subjects
Condition: Healthy
Intervention: Maraviroc; Fosamprenavir; Ritonavir
Intervention description: 300 mg BID; 1400 mg BID, 700 mg BID or 1400 mg QD; 100 mg BID, 100 mg QD
Intervention MeSH terms: Ritonavir; Fosamprenavir; Maraviroc
Phase: Phase 2
Study type: Interventional
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy Subjects; Pharmacokinetics study; Pharmacokinetics of medications

Summary:

      To date, no study has investigated whether there is a drug interaction between the protease
      inhibitor fosamprenavir and the entry inhibitor maraviroc. COL112237 is a randomized,
      open-label, 6-arm, 3-period, drug interaction study to assess steady-state plasma amprenavir
      (APV) and maraviroc (MVC) pharmacokinetics in 48 healthy, HIV-negative adults after
      administration of a 7-day regimen of MVC 300mg 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 MVC 300mg 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.
    

Eligibility 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.

               -  child-bearing 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
                  antiinflammatory 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.