Phase 1
N=16
Pharmacokinetics of MK-3682B in Participants With Moderate to Severe Renal Insufficiency (MK-3682B-030)
Hepatitis C
Bottom Line
View on ClinicalTrials.gov: NCT02661126 ↗Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Dec 2018
Primary outcome: Primary: Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682) — 8.55; 4.23 uM*hr
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- MK-3682B (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Aug 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682) |
8.55; 4.23 | — |
| PRIMARY AUC From Dosing to Infinity (AUC0-∞) of Uprifosbuvir |
8.56; 4.28 | — |
| PRIMARY AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir |
8.54; 4.24 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of Uprifosbuvir |
3030; 1570 | — |
| PRIMARY Plasma Concentration 24 Hours Post-dose (C24) of Uprifosbuvir |
3.65 | — |
| PRIMARY Time to Reach Maximum Plasma Concentration (Tmax) of Uprifosbuvir |
1.00; 1.00 | — |
| PRIMARY Apparent Total Body Clearance (CL/F) of Uprifosbuvir |
96.3; 193 | — |
| PRIMARY Apparent Volume of Distribution (Vz/F) of Uprifosbuvir |
290; 724 | — |
| PRIMARY Apparent Terminal Half-life in Plasma (t½) of Uprifosbuvir |
2.09; 2.60 | — |
| PRIMARY AUC0-last of Uprifosbuvir Metabolite M5 |
14.8; 7.62 | — |
| PRIMARY AUC0-∞ of Uprifosbuvir Metabolite M5 |
16.2; 7.99 | — |
| PRIMARY AUC0-24 of Uprifosbuvir Metabolite M5 |
4.59; 2.67 | — |
| PRIMARY Cmax of Uprifosbuvir Metabolite M5 |
321; 173 | — |
| PRIMARY C24 of Uprifosbuvir Metabolite M5 |
262; 129 | — |
| PRIMARY Tmax of Uprifosbuvir Metabolite M5 |
20.00; 13.00 | — |
| PRIMARY Lag Time (Tlag) of Uprifosbuvir Metabolite M5 |
2.00; 2.00 | — |
| PRIMARY t½ of Uprifosbuvir Metabolite M5 |
26.27; 25.33 | — |
| PRIMARY AUC0-last of Uprifosbuvir Metabolite M6 |
63.9; 33.5 | — |
| PRIMARY AUC0-∞ of Uprifosbuvir Metabolite M6 |
71.4; 36.2 | — |
| PRIMARY AUC0-24 of Uprifosbuvir Metabolite M6 |
27.2; 13.9 | — |
| PRIMARY Cmax of Uprifosbuvir Metabolite M6 |
1540; 906 | — |
| PRIMARY C24 of Uprifosbuvir Metabolite M6 |
905; 466 | — |
| PRIMARY Tmax of Uprifosbuvir Metabolite M6 |
8.00; 3.50 | — |
| PRIMARY t½ of Uprifosbuvir Metabolite M6 |
33.58; 30.55 | — |
| PRIMARY AUC0-last of Grazoprevir (MK-5172) |
0.974; 0.730 | — |
| PRIMARY AUC0-∞ of Grazoprevir |
1.32; 0.826 | — |
| PRIMARY AUC0-24 of Grazoprevir |
0.436; 0.380 | — |
| PRIMARY Cmax of Grazoprevir |
67.5; 54.7 | — |
| PRIMARY C24 of Grazoprevir |
9.41; 7.36 | — |
| PRIMARY Tmax of Grazoprevir |
2.00; 2.25 | — |
| PRIMARY CL/F of Grazoprevir |
99.1; 158 | — |
| PRIMARY Vz/F of Grazoprevir |
6030; 9750 | — |
| PRIMARY t½ of Grazoprevir |
42.21; 42.85 | — |
| PRIMARY AUC0-last of Ruzasvir (MK-8408) |
2.07; 1.32 | — |
| PRIMARY AUC0-∞ of Ruzasvir |
2.19; 1.40 | — |
| PRIMARY AUC0-24 of Ruzasvir |
1.11; 0.744 | — |
| PRIMARY Cmax of Ruzasvir |
117; 80.9 | — |
| PRIMARY C24 of Ruzasvir |
23.9; 15.5 | — |
| PRIMARY Tmax of Ruzasvir |
3.00; 3.00 | — |
| PRIMARY CL/F of Ruzasvir |
31.0; 48.8 | — |
| PRIMARY Vz/F of Ruzasvir |
1410; 2060 | — |
| PRIMARY t½ of Ruzasvir |
31.50; 29.31 | — |
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
Data sourced from ClinicalTrials.gov (NCT02661126). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.