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

NCT01537900 | Completed Phase 1 Results

• 2 other identifiers: 5172-0102011-000435-83
• Study Type: interventional
• Target: 4
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (3)

• Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir

  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.

  4, 8, and 24 hours post-dose on Day 7

• Hepatic Concentration of GZR (C[H]Xhr)

  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.

  4, 8, 24, and 72 hours post-dose on Day 7

• Apparent Terminal Hepatic Half-life (t[H]½ ) of GZR

  t(H)1/2 is a measure of the time required for the maximum post-dose liver concentration of GZR to decrease by 50%.

  4, 8, 24, and 72 hours post-dose on Day 7

Secondary Outcomes (5)

• Plasma AUC[0-24 hr] of GZR

  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

• Maximum Plasma Concentration (Cmax) of GZR

  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

• Lowest Plasma Concentration (Ctrough) of GZR

  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

• Time to Maximum Plasma Concentration (Tmax) of GZR

  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

• Plasma t½ of GZR

  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

Study Arms (1)

Grazoprevir 100 mg

EXPERIMENTAL

Participants received GZR 100 mg once daily (q.d.) for 7 days. Liver FNA was performed on Day 7.

Drug: Grazoprevir

Interventions

Grazoprevir DRUG

GZR 100 mg tablet by mouth q.d. for 7 days.

Also known as: MK-5172

Grazoprevir 100 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hepatitis C

Interventions

grazoprevir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2012
• First Posted: February 23, 2012
• Study Start: October 1, 2013
• Primary Completion: July 31, 2014
• Study Completion: July 31, 2014
• Last Updated: September 14, 2018
• Results First Posted: March 4, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share