Pharmacokinetics of MK-3682B in Participants With Moderate to Severe Renal Insufficiency (MK-3682B-030)

Overview

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.

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 26, 2016

Interventions

  • Drug: MK-3682B
    • FDC oral tablet containing 225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir.

Arms, Groups and Cohorts

  • Experimental: Moderate RI Participants
    • Participants with an estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73m^2 to <60 mL/min/1.73m^2 take 2 MK-3682B FDC tablets on Day 1 after fasting for 10 hours.
  • Experimental: Severe RI Participants
    • Participants with an eGFR of ≥15 mL/min/1.73m^2 to <30 mL/min/1.73m^2 take 2 MK-3682B FDC tablets on Day 1 after fasting for 10 hours.
  • Experimental: Healthy Participants
    • Healthy participants (creatinine clearance [CLcr] ≥80 mL/min) take 2 MK-362B FDC tablets on Day 1 after fasting for 10 hours. Healthy participants are matched to RI participants based on mean age, body mass index (BMI) and gender.

Clinical Trial Outcome Measures

Primary Measures

  • Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682)
    • Time Frame: 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
    • AUC0-last is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to the time of the last quantifiable (< lower limit of quantification [LLOQ]) sample following oral administration of MK-3682B.
  • AUC From Dosing to Infinity (AUC0-∞) of Uprifosbuvir
    • Time Frame: 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
    • AUC0-∞ is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
  • AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir
    • Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
    • AUC0-24 is a measure of total exposure to uprifosbuvir in plasma from dosing to 24 hours following oral administration of MK-3682B.
  • Maximum Plasma Concentration (Cmax) of Uprifosbuvir
    • Time Frame: 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
    • Cmax is the maximum amount of uprifosbuvir in plasma following oral administration of MK-3682B.
  • Plasma Concentration 24 Hours Post-dose (C24) of Uprifosbuvir
    • Time Frame: 24 hours post-dose
    • C24 is the plasma concentration of uprifosbuvir 24 hours following oral administration of MK-3682B.
  • Time to Reach Maximum Plasma Concentration (Tmax) of Uprifosbuvir
    • Time Frame: 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
    • Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir following oral administration of MK-3682B.
  • Apparent Total Body Clearance (CL/F) of Uprifosbuvir
    • Time Frame: 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
    • CL/F is the apparent total body clearance of uprifosbuvir following oral administration of MK-3682B.
  • Apparent Volume of Distribution (Vz/F) of Uprifosbuvir
    • Time Frame: 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
    • Vz/F is the apparent volume of distribution of uprifosbuvir following oral administration of MK-3682B.
  • Apparent Terminal Half-life in Plasma (t½) of Uprifosbuvir
    • Time Frame: 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
    • t1/2 is the amount of time required to clear 50% of uprifosbuvir from plasma following oral administration of MK-3682B.
  • AUC0-last of Uprifosbuvir Metabolite M5
    • Time Frame: 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
    • AUC0-last is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from the start of dosing to the time of the last quantifiable (<LLOQ) sample following oral administration of MK-3682B.
  • AUC0-∞ of Uprifosbuvir Metabolite M5
    • Time Frame: 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
    • AUC0-∞ is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from the start of dosing to infinity following oral administration of MK-3682B.
  • AUC0-24 of Uprifosbuvir Metabolite M5
    • Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
    • AUC0-24 is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from dosing to 24 hours following oral administration of MK-3682B.
  • Cmax of Uprifosbuvir Metabolite M5
    • Time Frame: 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
    • Cmax is the maximum amount of uprifosbuvir metabolite M5 in plasma following oral administration of MK-3682B.
  • C24 of Uprifosbuvir Metabolite M5
    • Time Frame: 24 hours post-dose
    • C24 is the plasma concentration of uprifosbuvir metabolite M5 24 hours following oral administration of MK-3682B.
  • Tmax of Uprifosbuvir Metabolite M5
    • Time Frame: 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
    • Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M5 following oral administration of MK-3682B.
  • Lag Time (Tlag) of Uprifosbuvir Metabolite M5
    • Time Frame: 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
    • Tlag is the time from dosing to first appearance in plasma of uprifosbuvir metabolite M5 following oral administration of MK-3682B.
  • t½ of Uprifosbuvir Metabolite M5
    • Time Frame: 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
    • t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M5 from plasma following oral administration of MK-3682B.
  • AUC0-last of Uprifosbuvir Metabolite M6
    • Time Frame: 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
    • AUC0-last is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from the start of dosing to the time of the last quantifiable (<LLOQ) sample following oral administration of MK-3682B.
  • AUC0-∞ of Uprifosbuvir Metabolite M6
    • Time Frame: 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
    • AUC0-∞ is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from the start of dosing to infinity following oral administration of MK-3682B.
  • AUC0-24 of Uprifosbuvir Metabolite M6
    • Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
    • AUC0-24 is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from dosing to 24 hours following oral administration of MK-3682B.
  • Cmax of Uprifosbuvir Metabolite M6
    • Time Frame: 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
    • Cmax is the maximum amount of uprifosbuvir metabolite M6 in plasma following oral administration of MK-3682B.
  • C24 of Uprifosbuvir Metabolite M6
    • Time Frame: 24 hours post-dose
    • C24 is the plasma concentration of uprifosbuvir metabolite M6 24 hours following oral administration of MK-3682B.
  • Tmax of Uprifosbuvir Metabolite M6
    • Time Frame: 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
    • Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M6 following oral administration of MK-3682B.
  • t½ of Uprifosbuvir Metabolite M6
    • Time Frame: 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
    • t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M6 from plasma following oral administration of MK-3682B.
  • AUC0-last of Grazoprevir (MK-5172)
    • Time Frame: 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
    • AUC0-last is a measure of total exposure to grazoprevir in plasma from the start of dosing to the time of the last quantifiable (<LLOQ) sample following oral administration of MK-3682B.
  • AUC0-∞ of Grazoprevir
    • Time Frame: 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
    • AUC0-∞ is a measure of total exposure to grazoprevir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
  • AUC0-24 of Grazoprevir
    • Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
    • AUC0-24 is a measure of total exposure to grazoprevir in plasma from the start of dosing to 24 hours post-dose following oral administration of MK-3682B.
  • Cmax of Grazoprevir
    • Time Frame: 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
    • Cmax is the maximum amount of grazoprevir in plasma following oral administration of MK-3682B.
  • C24 of Grazoprevir
    • Time Frame: 24 hours post-dose
    • C24 is the plasma concentration of grazoprevir 24 hours following oral administration of MK-3682B.
  • Tmax of Grazoprevir
    • Time Frame: 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
    • Tmax is the time required to reach the maximum post-dose plasma concentration of grazoprevir following oral administration of MK-3682B.
  • CL/F of Grazoprevir
    • Time Frame: 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
    • CL/F is the apparent total body clearance of grazoprevir following oral administration of MK-3682B.
  • Vz/F of Grazoprevir
    • Time Frame: 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
    • Vz/F is the apparent volume of distribution of grazoprevir following oral administration of MK-3682B.
  • t½ of Grazoprevir
    • Time Frame: 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
    • t1/2 is the amount of time required to clear 50% of grazoprevir from plasma following oral administration of MK-3682B.
  • AUC0-last of Ruzasvir (MK-8408)
    • Time Frame: 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
    • AUC0-last is a measure of total exposure to ruzasvir in plasma from the start of dosing to the time of the last quantifiable (<LLOQ) sample following oral administration of MK-3682B.
  • AUC0-∞ of Ruzasvir
    • Time Frame: 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
    • AUC0-∞ is a measure of total exposure to ruzasvir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
  • AUC0-24 of Ruzasvir
    • Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
    • AUC0-24 is a measure of total exposure to ruzasvir in plasma from dosing to 24 hours following oral administration of MK-3682B.
  • Cmax of Ruzasvir
    • Time Frame: 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
    • Cmax is the maximum amount of ruzasvir in plasma following oral administration of MK-3682B.
  • C24 of Ruzasvir
    • Time Frame: 24 hours post-dose
    • C24 is the plasma concentration of ruzasvir 24 hours following oral administration of MK-3682B.
  • Tmax of Ruzasvir
    • Time Frame: 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
    • Tmax is the time required to reach the maximum post-dose plasma concentration of ruzasvir following oral administration of MK-3682B.
  • CL/F of Ruzasvir
    • Time Frame: 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
    • CL/F is the apparent total body clearance of ruzasvir following oral administration of MK-3682B.
  • Vz/F of Ruzasvir
    • Time Frame: 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
    • Vz/F is the apparent volume of distribution of ruzasvir following oral administration of MK-3682B.
  • t½ of Ruzasvir
    • Time Frame: 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
    • t1/2 is the amount of time required to clear 50% of ruzasvir from plasma following oral administration of MK-3682B.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Merck Sharp & Dohme LLC
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Director, Study Director, Merck Sharp & Dohme LLC

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.