Clinical trial NCT01537900: A Multiple Dose Study of Grazoprevir (MK-5172) in Hepatitis C-Infected Participants (MK-5172-010)
Official title: A Multiple Dose Study to Evaluate Pharmacokinetics and Hepatitis C Virus RNA Dynamics Following Administration of MK-5172 in Hepatitis C Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-02-23
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir
timeFrame: 4, 8, and 24 hours post-dose on Day 7
measure: Hepatic Concentration of GZR (C[H]Xhr)
timeFrame: 4, 8, 24, and 72 hours post-dose on Day 7
measure: Apparent Terminal Hepatic Half-life (t[H]½ ) of GZR
timeFrame: 4, 8, 24, and 72 hours post-dose on Day 7
Secondary outcomes:
measure: Plasma AUC[0-24 hr] of GZR
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
measure: Maximum Plasma Concentration (Cmax) of GZR
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
measure: Lowest Plasma Concentration (Ctrough) of GZR
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
measure: Time to Maximum Plasma Concentration (Tmax) of GZR
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
measure: Plasma t½ of GZR
timeFrame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: