Clinical trial NCT01937975: The Pharmacokinetics of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Participants With Renal Insufficiency (MK-5172-050)
Official title: An Open-Label Study to Investigate the Pharmacokinetics of MK-5172 and MK-8742 in Subjects With Renal Insufficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Hepatitis C
Renal Impairment
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-09-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir
timeFrame: Up to 24 hours postdose
measure: Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir
timeFrame: 24 hours postdose
measure: Maximum Plasma Concentration (Cmax) of Grazoprevir
timeFrame: Up to 120 hours postdose
measure: Time of Maximum Plasma Concentration (Tmax) of Grazoprevir
timeFrame: Up to 120 hours postdose
measure: Apparent Terminal Half-life (T1/2) of Grazoprevir
timeFrame: Up to 120 hours postdose
measure: Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir
timeFrame: Up to 24 hours postdose
measure: Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir
timeFrame: Up to 24 hours postdose
measure: Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir
timeFrame: Up to 24 hours postdose
measure: Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir
timeFrame: 24 hours postdose
measure: Maximum Plasma Concentration (Cmax) of Elbasvir
timeFrame: Up to 120 hours postdose
measure: Time of Maximum Plasma Concentration (Tmax) of Elbasvir
timeFrame: Up to 120 hours postdose
measure: Apparent Terminal Half-life (T1/2) of Elbasvir
timeFrame: Up to 120 hours postdose
measure: Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir
timeFrame: Up to 24 hours postdose
measure: Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir
timeFrame: Up to 24 hours postdose
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.