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A Multiple Dose Study of Grazoprevir (MK-5172) in Hepatitis C-Infected Participants (MK-5172-010)

This study has been completed.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp. Identifier:
First received: February 17, 2012
Last updated: March 1, 2017
Last verified: March 2017
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).

Condition Intervention Phase
Hepatitis C
Drug: Grazoprevir
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir [ Time Frame: 4, 8, and 24 hours post-dose on Day 7 ]
    Each participant was assigned to undergo Fine Needle Aspiration (FNA) to obtain liver tissue at different time points. Specifically, one participant underwent FNA at 4 hr post-dose only, another participant underwent FNA at 8 hr post-dose only, and a third participant underwent FNA at 24 hr post-dose only. (The fourth participant underwent FNA at 72 hr post-dose and therefore was not included in the calculation of AUC0-24hr.) Therefore, in calculating AUC0-24hr, there were only 3 data points: 1 data point at 4 hr post-dose, 1 data point at 8 hr post-dose, and 1 data point at 24 hr post-dose. The model assumed that drug concentration was at steady-state, and that the concentration at 24 hr post-dose was equal to the concentration at 0 hr post-dose.

  • Hepatic Concentration of GZR (C[H]Xhr) [ Time Frame: 4, 8, 24, and 72 hours post-dose on Day 7 ]
    C(H)Xhr of GZR was expressed as liver concentration (μmol GZR/L liver) using the concentration of the extracted liver sample (mass of the liver biopsy/0.2 mL solvent), and assuming that liver has the specific gravity of water (1 g/mL). The arithmetic mean C(H)Xhr concentration is based on the means of 4 FNA passes per participant in all 4 participants.

  • Apparent Terminal Hepatic Half-life (t[H]½ ) of GZR [ Time Frame: 4, 8, 24, and 72 hours post-dose on Day 7 ]
    t(H)1/2 is a measure of the time required for the maximum post-dose liver concentration of GZR to decrease by 50%.

Secondary Outcome Measures:
  • Plasma AUC[0-24 hr] of GZR [ Time Frame: 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 ]
    AUC0-24hr is a measure of the mean concentration of drug in plasma after dosing to 24 hours post-dose.

  • Maximum Plasma Concentration (Cmax) of GZR [ Time Frame: 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 ]
    Cmax is a measure of the maximum plasma concentration post-dose.

  • Lowest Plasma Concentration (Ctrough) of GZR [ Time Frame: 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 ]
    Ctrough is a measure of drug concentration 24 hours post-dose.

  • Time to Maximum Plasma Concentration (Tmax) of GZR [ Time Frame: 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 ]
    Tmax is a measure of time to reach maximum post-dose plasma drug concentration.

  • Plasma t½ of GZR [ Time Frame: 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 ]
    t1/2 is a measure of time for the maximum plasma concentration of GZR to decrease by 50%.

Enrollment: 4
Study Start Date: October 2013
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Grazoprevir 100 mg
Participants received GZR 100 mg once daily (q.d.) for 7 days. Liver FNA was performed on Day 7.
Drug: Grazoprevir
GZR 100 mg tablet by mouth q.d. for 7 days.
Other Name: MK-5172


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT01537900

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp. Identifier: NCT01537900     History of Changes
Other Study ID Numbers: 5172-010
2011-000435-83 ( EudraCT Number )
Study First Received: February 17, 2012
Results First Received: February 3, 2016
Last Updated: March 1, 2017
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description:

Additional relevant MeSH terms:
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections processed this record on April 28, 2017