The Pharmacokinetics of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Participants With Renal Insufficiency (MK-5172-050)

NCT01937975 | Completed Phase 1 Results

• 1 other identifier: 5172-050
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Grazoprevir (MK-5172) and Elbasvir (MK-8742) were studied as the principal components of combination oral therapy for hepatitis C virus (HCV). The study examined the pharmacokinetic (PK) profiles of Grazoprevir and Elbasvir following 10 days of dosing in participants with end stage renal disease (ESRD) on hemodialysis (HD) or participants with severe renal impairment. Both groups were compared to healthy matched controls.

Conditions

Chronic Hepatitis C; Renal Impairment

Outcome Measures

Primary Outcomes (14)

• Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir

  Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

  Up to 24 hours postdose

• Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir

  Blood for determination of Grazoprevir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

  24 hours postdose

• Maximum Plasma Concentration (Cmax) of Grazoprevir

  Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9

  Up to 120 hours postdose

• Time of Maximum Plasma Concentration (Tmax) of Grazoprevir

  Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9

  Up to 120 hours postdose

• Apparent Terminal Half-life (T1/2) of Grazoprevir

  Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10

  Up to 120 hours postdose

• Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir

  Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

  Up to 24 hours postdose

• Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir

  Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10

  Up to 24 hours postdose

• Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir

  Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

  Up to 24 hours postdose

• Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir

  Blood for determination of Elbasvir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

  24 hours postdose

• Maximum Plasma Concentration (Cmax) of Elbasvir

  Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9

  Up to 120 hours postdose

• Time of Maximum Plasma Concentration (Tmax) of Elbasvir

  Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9

  Up to 120 hours postdose

• Apparent Terminal Half-life (T1/2) of Elbasvir

  Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10

  Up to 120 hours postdose

• Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir

  Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

  Up to 24 hours postdose

• Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir

  Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10

  Up to 24 hours postdose

Study Arms (3)

Participants with End Stage Renal Disease on Hemodialysis

EXPERIMENTAL

Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days..

Drug: Grazoprevir; Drug: Elbasvir

Participants with Severe Renal Impairment

EXPERIMENTAL

Participants with Severe Renal Impairment (estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.

Drug: Grazoprevir; Drug: Elbasvir

Healthy Participants

EXPERIMENTAL

Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.

Drug: Grazoprevir; Drug: Elbasvir

Interventions

Grazoprevir DRUG

100 mg oral tablet administered once a day for 10 days

Healthy Participants; Participants with End Stage Renal Disease on Hemodialysis; Participants with Severe Renal Impairment

Elbasvir DRUG

50 mg oral tablet administered once a day for 10 days

Healthy Participants; Participants with End Stage Renal Disease on Hemodialysis; Participants with Severe Renal Impairment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Participants
• For a female of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to the first dose and throughout the study or be using an acceptable birth control method. Females of non-childbearing potential must have undergone a sterilization procedure at least 6 months prior to the first dose
• Non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse during the trial and for 90 days after stopping the study medication and agree not to donate sperm during this time period Participants with ESRD on HD
• Maintained on a stable regimen of HD within 3 months prior to first dosing Participants with Severe Renal Impairment
• Estimated glomerular filtration rate (eGFR) at screening is \< 30 mL/min/1.73m\^2 Healthy Controls
• Participant is within ± 10 years of the mean age and within 10% of the mean body mass index of severe renal impairment participants
• eGFR at screening is \>=80 mL/min/1.73m\^2

You may not qualify if:

• All Participants
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease whose current condition is considered unstable
• History or presence of alcoholism and drug abuse within the past 6 months
• Female participants who are pregnant or lactating
• Regular user of any medication (including over the counter) that would significantly alter GFR
• Donation of blood or significant blood loss within 56 days prior to the first dose of study medication(s)
• Plasma donation within 7 days prior to the first dose of study medication(s)
• A renal transplant or nephrectomy Participants with ESRD or Severe Renal Impairment
• Rapidly fluctuating renal function

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Caro L, Wenning L, Feng HP, Guo Z, Du L, Bhagunde P, Fandozzi C, Panebianco D, Marshall WL, Butterton JR, Iwamoto M, Yeh WW. Pharmacokinetics of elbasvir and grazoprevir in subjects with end-stage renal disease or severe renal impairment. Eur J Clin Pharmacol. 2019 May;75(5):665-675. doi: 10.1007/s00228-018-2585-3. Epub 2019 Jan 25.

  PMID: 30680407 RESULT

MeSH Terms

Conditions

Hepatitis C, Chronic; Renal Insufficiency

Interventions

grazoprevir; elbasvir

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2013
• First Posted: September 10, 2013
• Study Start: September 6, 2013
• Primary Completion: December 17, 2013
• Study Completion: December 17, 2013
• Last Updated: June 12, 2019
• Results First Posted: March 4, 2016

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share