A Drug Interaction Study to Assess the Pharmacokinetics of Narlaprevir and Antiretroviral Drugs
Condition: Healthy
Intervention: Narlaprevir; Ritonavir; Tenofovir Disoproxil Fumarate; Raltegravir
Intervention description: 100 mg, film-coated tablets, taken as 200 mg per os daily; 100 mg, film-coated tablets, taken as 100 mg per os daily; 300 mg, film-coated tablets, taken as 300 mg per os daily; 400 mg, film-coated tablets, taken as 400 mg per os daily
Intervention MeSH terms: Ritonavir; Tenofovir; Raltegravir Potassium
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 21 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: hepatitis C; chronic; pharmacokinetics; HIV; coinfection; concomitant therapy

Summary:

      The study purpose is to evaluate the potential for a pharmacokinetic drug-drug interaction,
      safety and tolerability when Narlaprevir, Ritonavir (used as a metabolic inhibitor) and
      Tenofovir disoproxil fumarate (part 1) and Narlaprevir, Ritonavir and Raltegravir (part 2)
      are administered in combination to healthy volunteers.
    

Eligibility criteria:

        Inclusion Criteria (the subject must meet all the criteria listed below for entry at
        baseline and at Days -1 and 1 before each treatment Period):

          -  Subjects must be willing to give written informed consent for the trial and able to
             adhere to dose and visit schedules.

          -  Subjects having a Body Mass Index (BMI) between 18,5 and 30 kg/m^2, inclusive.

          -  Subjects should diagnosed as "healthy": no pathology of the gastrointestinal tract,
             liver, kidneys, cardiovascular system, central nervous system (previously carried out
             by standard clinical and lab tests which did not reveal the presence of any diseases.
             Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must not exceed
             the normal range; QT interval calculated by Bazett's formula (QTcB) for men should be
             ≤ 450 ms and ≤ 470 ms for women, the interval PR should be ≤ 200 ms).

          -  Vital sign measurements (taken after ~3 minutes in a supine or sitting position) must
             be within the following ranges:

               1. systolic blood pressure, 100 - 130 mm Hg;

               2. diastolic blood pressure, 60 -90 mm Hg;

               3. pulse rate, 60-80 bpm.

          -  Female subjects must be:

               1. postmenopausal (defined as 12 months with no menses; age > 40 years and with a
                  follicle-stimulating hormone (FSH) level of >40 u/mL);

               2. surgically sterilized at least 3 months prior to baseline (e.g., documented
                  hysterectomy or tubal ligation).

          -  Men must agree to use a medically accepted method of contraception (condom and
             spermicide) during the trial and for 3 months after stopping the medication.

        Exclusion Criteria (the subject will be excluded from entry if any of the criteria listed
        below are met at baseline):

          -  Females with childbearing potential.

          -  Subjects who, in the opinion of the investigator, will not be able to participate
             optimally in the study.

          -  Positive results for hepatitis B surface antigen, hepatitis C antibodies or HIV,
             positive RW results.

          -  Allergic reactions in history.

          -  Intolerance to medication.

          -  Chronic disease of cardiovascular, bronchopulmonary, and/or neuroendocrine systems,
             gastrointestinal, liver, pancreas, kidney and/or blood disease.

          -  History or presence of impaired renal function, lactase deficiency, lactose
             intolerance, glucose-galactose malabsorption.

          -  History of urinary obstruction or difficulty in voiding.

          -  Gastrointestinal surgery in history (except of appendectomy).

          -  Acute infections less than 4 weeks before participation in the study.

          -  Subjects with a medical history of osteopenia and/or osteoporosis.

          -  Regular administration of any medicines less than 4 weeks before participation in the
             study.

          -  Administration of medicines with marked influence on hemodynamics, liver function et
             al (barbiturates, omeprazole, cimetidine et al) less than 30 days before participation
             in the study.

          -  Blood donation (450 ml or more of blood or plasma) less than 2 months before
             participation in the study.

          -  Intake of more than 10 units of alcohol in a week (1 unit of alcohol is equal to 0.5 L
             of beer, 200 mL of wine or 50 mL of spirits) or history of drug abuse or alcoholism.

          -  Smoking of more than 10 cigarettes or equivalent tobacco use per day.

          -  Participation in phase 1 clinical trial less than 3 months before participation in the
             study.

          -  Positive screen for drugs abuse and drugs use.

          -  Subjects with a medical history of psychiatric or personality disorders that in the
             opinion of the investigator and sponsor, affects the subject's ability to participate
             in the trial.

          -  Subjects who are part of the study staff personnel or family members of the study
             staff personnel.