Clinical trial NCT02661126: Pharmacokinetics of MK-3682B in Participants With Moderate to Severe Renal Insufficiency (MK-3682B-030)
Official title: A Two-Part, Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-3682B (MK-3682/MK-5172/MK-8408 Fixed Dose Combination) When Administered to Subjects With Moderate and Severe Renal Insufficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2016-01-22
Enrollment: 16
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: The purpose of this study is to compare the plasma pharmacokinetics (PK) of single doses of MK-3682B, a fixed dose combination (FDC) tablet containing uprifosbuvir (MK-3682) + grazoprevir (MK-5172) + ruzasvir (MK-8408) in participants with moderate (Part 1) and severe (Part 2) renal insufficiency (RI) to plasma PK in healthy participants.


Eligibility criteria: Inclusion Criteria:

All Participants:

* Healthy adult males or females 18-80 years of age at screening
* Continuous non-smokers or moderate smokers (≤ 20 cigarettes/day or the equivalent) and agrees to consume no more than 10 cigarettes per day during the study period
* BMI ≥ 18 and ≤ 40.0 kg/m\^2
* Agrees not to become pregnant or father a child during participation in the study
* Females of childbearing potential must either be abstinent for 14 days prior to dosing and throughout the study or be using an acceptable birth control method
* Vasectomized or non-vasectomized males must agree to use a condom with spermicide or abstain from sexual intercourse from the first dose until 90 days after dosing
* Males must agree not to donate sperm from dosing until 90 days after dosing

Moderate and Severe RI Participants:

* Baseline health is judged to be stable based on medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the Investigator
* Has had no clinically significant change in renal status at least 1 month prior to dosing and is not currently or has not previously been on hemodialysis
* Moderate RI: has baseline eGFR ≥ 30 mL/min/1.73m\^2 and \< 60 mL/min/1.73m\^2, based on the Modification of Diet in Renal Disease (MDRD) equation at screening
* Severe RI: has baseline eGFR ≥ 15 mL/min/1.73m\^2 and \< 30 mL/min/1.73m\^2, based on the MDRD equation at screening

Healthy Participants:

* Is within ± 10 years of the mean age of moderate and severe RI arms
* BMI is within 10% of the mean BMI of participants with moderate and severe RI arms
* Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECGs, as deemed by the Investigator
* Baseline CLcr ≥ 80 mL/min based on Cockcroft-Gault equation at screening

Exclusion Criteria:

* Is mentally or legally incapacitated or has significant emotional problems at the time of the screening
* History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator
* History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk by participating in the study
* Is female and pregnant or lactating
* Positive results for the urine or saliva drug screen or urine or breath alcohol screen at screening or check-in unless the positive drug screen is due to prescription drug use that is approved by the Investigator and Sponsor
* Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
* Seated heart rate is equal to or lower than 44 beats per minute (bpm) or higher than 100 bpm at screening
* Has had a renal transplant or has had nephrectomy
* Donation of blood or had significant blood loss within 56 days prior to dosing of study drug, or donation of plasma within 7 days prior to dosing
* Has participated in another clinical trial within 28 days prior to dosing of study drug

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682)
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC From Dosing to Infinity (AUC0-∞) of Uprifosbuvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
measure: Maximum Plasma Concentration (Cmax) of Uprifosbuvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: Plasma Concentration 24 Hours Post-dose (C24) of Uprifosbuvir
timeFrame: 24 hours post-dose
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Uprifosbuvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: Apparent Total Body Clearance (CL/F) of Uprifosbuvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: Apparent Volume of Distribution (Vz/F) of Uprifosbuvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: Apparent Terminal Half-life in Plasma (t½) of Uprifosbuvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-last of Uprifosbuvir Metabolite M5
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-∞ of Uprifosbuvir Metabolite M5
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-24 of Uprifosbuvir Metabolite M5
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
measure: Cmax of Uprifosbuvir Metabolite M5
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: C24 of Uprifosbuvir Metabolite M5
timeFrame: 24 hours post-dose
measure: Tmax of Uprifosbuvir Metabolite M5
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: Lag Time (Tlag) of Uprifosbuvir Metabolite M5
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: t½ of Uprifosbuvir Metabolite M5
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-last of Uprifosbuvir Metabolite M6
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-∞ of Uprifosbuvir Metabolite M6
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-24 of Uprifosbuvir Metabolite M6
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
measure: Cmax of Uprifosbuvir Metabolite M6
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: C24 of Uprifosbuvir Metabolite M6
timeFrame: 24 hours post-dose
measure: Tmax of Uprifosbuvir Metabolite M6
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: t½ of Uprifosbuvir Metabolite M6
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-last of Grazoprevir (MK-5172)
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-∞ of Grazoprevir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-24 of Grazoprevir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
measure: Cmax of Grazoprevir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: C24 of Grazoprevir
timeFrame: 24 hours post-dose
measure: Tmax of Grazoprevir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: CL/F of Grazoprevir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: Vz/F of Grazoprevir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: t½ of Grazoprevir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-last of Ruzasvir (MK-8408)
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-∞ of Ruzasvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: AUC0-24 of Ruzasvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
measure: Cmax of Ruzasvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: C24 of Ruzasvir
timeFrame: 24 hours post-dose
measure: Tmax of Ruzasvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: CL/F of Ruzasvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: Vz/F of Ruzasvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
measure: t½ of Ruzasvir
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: