A Multiple Dose Study of Grazoprevir (MK-5172) in Hepatitis C-Infected Participants (MK-5172-010)
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: Grazoprevir
Intervention description: GZR 100 mg tablet by mouth q.d. for 7 days.
Intervention MeSH terms: Grazoprevir
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The goal of this study was to compare hepatic pharmacokinetics (PK) derived from liver tissue
      to plasma PK after administration of grazoprevir (MK-5172) to participants with chronic
      hepatitis C virus (HCV) infection. Participants will be randomized to one of four different
      liver ultrasound-guided Fine Needle Aspirate (FNA) schedules (at 4-, 8-, 24-, or 72-hours
      after the Day 7 dose).
    

Eligibility criteria:

        Inclusion criteria:

          -  has a Body Mass Index (BMI) ≥18.5 kg/m² and ≤36.0 kg/m²

          -  has chronic compensated, genotype 1 HCV infection

          -  has no cirrhosis of the liver as confirmed by FibroSure®/Fibro Test® and/or local
             country procedure (e.g. transient elastography/Fibroscan)

          -  does not require anticoagulants, nonsteroidal anti-inflammatory agents, and aspirin
             for at least fourteen (14) days preceding the initial liver biopsy and continuing
             throughout the entire study

          -  if is a female participant of reproductive potential, is willing to use 2 medically
             acceptable forms of contraception for 2 weeks prior to start of treatment through 2
             weeks after last study treatment

          -  if is a male participant with a partner(s) of reproductive potential, is willing to
             use 2 medically acceptable forms of contraception from first dose to 90 days after
             last dose

        Exclusion criteria:

          -  has a history of stroke, chronic seizures, or major neurological disorder

          -  has received previous treatment with a direct-acting antiviral (DAA)

          -  has evidence of high grade bridging fibrosis from prior liver biopsy within 3 years of
             study entry

          -  has evidence or history of chronic hepatitis not caused by HCV infection including but
             not limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH),
             drug-induced hepatitis, or autoimmune hepatitis

          -  has clinical or laboratory evidence of cirrhosis or other advanced liver disease

          -  has decompensated liver disease as indicated by a history of ascites, hepatic
             encephalopathy, or bleeding esophageal varices

          -  has been diagnosed with, or suspected of having, hepatocellular carcinoma (HCC)

          -  has clinically significant abnormality on an electrocardiogram (ECG)

          -  is co-infected with human immunodeficiency virus (HIV)

          -  is positive for Hepatitis B surface antigen (HBsAg) or other evidence of active
             Hepatitis B infection

          -  has a history of gastric bypass surgery, bowel resection or other disorder that may
             interfere with absorption

          -  has a history of clinically significant uncontrolled endocrine, gastrointestinal,
             cardiovascular, hematological, immunological, renal, respiratory, or genitourinary
             abnormalities or diseases

          -  has clinically significant neoplastic disease

          -  uses alcohol to excess, defined as greater than 3 glasses of alcoholic beverages (1
             glass is approximately equivalent to: beer [354 mL], wine [118 mL], or distilled
             spirits [29.5 mL]) per day

          -  is a current regular user (including use of any illicit drugs) or history of drug
             (including alcohol) abuse within the last 3 months

          -  has undergone surgery, donation of 1 unit of blood (approximately 500 mL) or
             participation in another investigational study within a period of 4 weeks prior to the
             screening visit

          -  has a history of multiple and/or severe allergies, or anaphylactic reaction or
             intolerability to prescription or nonprescription drugs or food

          -  is pregnant or lactating

          -  is expecting to donate eggs or sperm