Comparison of Safety and Resulting Blood Level Profiles After Administration of a New Boceprevir Tablet Versus Its Current Capsule Formulation for Treatment of Chronic Hepatitis C (P06992)(COMPLETED)
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: boceprevir; boceprevir; boceprevir; boceprevir
Intervention description: Boceprevir (tablet or capsule) at 800 mg administered under either fed or fasted conditions.; Boceprevir (tablet or capsule) at 800 mg administered under either fed or fasted conditions.; Boceprevir (tablet or capsule) at 800 mg administered under either fed or fasted conditions.; Boceprevir (tablet or capsule) at 800 mg administered under either fed or fasted conditions.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 177.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: boceprevir; hepatitis C; bioequivalence; SCH 503034

Summary:

      This is a single-dose, randomized, cross-sectional comparison study examining the relative
      safety and resulting blood level profiles after administration of a new boceprevir tablet
      formulation versus its current capsule formulation for treatment of chronic hepatitis C. In
      Part 1 of the study participants will receive boceprevir tablets and capsules under fed
      conditions. In Part 2 of the study a new group of participants will receive boceprevir
      tablets and capsules under fasted conditions.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must be willing to give written informed consent for the trial and able to
             adhere to dose and visit schedules.

          -  Subjects must be willing to give written informed consent for pharmacogenetic

        testing, and able to adhere to applicable visit schedules.

        - Subjects of either gender and of any race between the ages of 18 and 65

        years, inclusive, having a Body Mass Index (BMI) between 18 and 32,

        inclusive. BMI = weight (kg)/height (m)^2. (Individuals with values outside (or

        indicate lower or higher) of these ranges may be enrolled if clinically

        acceptable to the investigator and sponsor.)

          -  Subjects' clinical laboratory tests (complete blood count [CBC], blood chemistry, and
             urinalysis) must be within normal limits or clinically acceptable to the investigator
             and within an allowed expanded range supplied by sponsor. However, subject's liver
             function test results (ie, aspartate aminotransferase [AST], alanine aminotransferase
             [ALT]) must not be elevated above normal limits at Screening and on Day -1. No
             rescreening of liver function tests will be allowed.

          -  Subjects must be free of any clinically significant disease that would interfere with
             the study evaluations.

          -  The Screening 12 lead electrocardiogram [ECG] conduction intervals must be within
             gender specific normal range (e.g, ECG QTcB,measure in males ≤430 msec and QTcB
             measure in females ≤450 msec, PR interval ≤200 msec).

          -  Vital sign measurements (taken after ~3 minutes in a sitting position) must be

        within the following ranges: (Individuals with values outside of these ranges

        may be enrolled if clinically acceptable to the investigator and sponsor.)

          1. oral body temperature, between 35.0°C and 37.5°C

          2. systolic blood pressure, 90 to 140 mm Hg

          3. diastolic blood pressure, 45 to 90 mm Hg

          4. pulse rate, 40 to 100 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, and serum E2 <
             73 pmol/L), or

          2. surgically sterilized at least 3 months prior to baseline (eg, documented

             hysterectomy or tubal ligation), or

          3. premenopausal and if unsterilized must have used a medically

             accepted method of contraception for 3 months (or abstained from

             sexual intercourse) prior to the screening period, and agree to use a

             medically accepted method of contraception during the trial (including

             the screening period prior to receiving trial medication) and for

             2 months after stopping the trial medication. An acceptable method of

             contraception includes one of the following:

        i. stable oral, transdermal, injectable, or sustained-release vaginal

        hormonal contraceptive regimen without breakthrough uterine

        bleeding for 3 months prior to Screening; in addition, during

        study use of condom and/or spermicide (when marketed in the

        country).

        ii. intrauterine device (inserted at least 2 months prior to Screening

        visit); in addition, during study use of condom and/or spermicide

        (when marketed in the country).

        iii. condom (male or female) with spermicide (when marketed

        within the country),

        iv. diaphragm or cervical cap with spermicide (when marketed

        within the country) and condom (male),

        - Non-vasectomized men must agree to use a condom with spermicide or abstain from sexual
        intercourse, during the trial and for 1 month after stopping the medication.

        Exclusion Criteria:

          -  Female subjects who are pregnant, intend to become pregnant (within

             3 months of ending the study), or are breastfeeding.

          -  Subjects who, in the opinion of the investigator, will not be able to participate
             optimally in the study.

          -  Any surgical or medical condition which might significantly alter the

        absorption, distribution, metabolism or excretion of any drug. The investigator

        should be guided by evidence of any of the following, and be discussed with

        the sponsor prior to enrollment into the trial:

          1. history or presence of inflammatory bowel disease, ulcers,

             gastrointestinal or rectal bleeding;

          2. history of major gastrointestinal tract surgery such as gastrectomy,

             gastroenterostomy, or bowel resection;

          3. history of pancreatic injury or pancreatitis;

          4. history or presence of liver disease or liver injury;

          5. history or presence of impaired renal function as indicated by clinically

             significant elevation in creatinine, blood urea nitrogen [BUN]/urea, urinary albumin,
             or

             clinically significant urinary cellular constituents ; or

          6. history of urinary obstruction or difficulty in voiding.

             - Subject who has a history of any infectious disease within 4 weeks prior to

             drug administration that in the opinion of the investigator, affects the subject's
             ability to participate in the trial.

               -  Subjects who are positive for hepatitis B surface antigen, hepatitis C

             antibodies or human immunodeficiency virus [HIV].

             - Subjects who have a positive screen for drugs with a high potential for abuse

             (during the Screening period or clinical conduct of the trial).

             - Subjects with a 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 with a history of alcohol or drug abuse in the past 2 years.- Subjects who
             have donated blood in the past 60 days.

             - Subjects who have previously received boceprevir.

               -  Subjects who are currently participating in another clinical study or have

             participated in a clinical study (e.g., laboratory or clinical evaluation) within 30
             days of baseline.

             - Subjects who are part of the study staff personnel or family members of the

             study staff personnel.

               -  Subjects who have demonstrated allergic reactions (eg, food, drug, atopic

             reactions or asthmatic episodes) which, in the opinion of the investigator and

             sponsor, interfere with their ability to participate in the trial.

             - Subjects who smoke more than 10 cigarettes or equivalent tobacco use per

             day.

               -  Subjects who have a history of malignancy.

               -  Subjects who have received any prohibited treatment (prescription and non
                  prescription medication except acetaminophen, potent inhibitors and inducers of
                  cytochrome P3A [CYP3A4], or vitamins and herbals) more recently than the
                  indicated washout period prior to Randomization which, in the opinion of the
                  investigator and sponsor, interferes with their ability to participate in the
                  trial.