Hepatitis CPhase 1NCT02661126
Pharmacokinetics of MK-3682B in Participants With Moderate to Severe Renal Insufficiency (MK-3682B-030)
A Phase 1 study testing MK-3682B in people with Hepatitis C, run by Merck Sharp & Dohme LLC.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C
- What is being tested?
- MK-3682B
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- No sites listed yet
- Study dates
- 19 Jan 2016to 26 Aug 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
About this study
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
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.
- Conditions
- Hepatitis C
- Being tested
- MK-3682B
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-3682BDrug
FDC oral tablet containing 225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir.
| Study group | Role | What they receive |
|---|---|---|
| Moderate RI Participants | Experimental | 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. Receives: Drug: MK-3682B |
| Severe RI Participants | Experimental | 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. Receives: Drug: MK-3682B |
| Healthy Participants | Experimental | 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. Receives: Drug: MK-3682B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682)
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.
Measured: 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
AUC From Dosing to Infinity (AUC0-∞) of Uprifosbuvir
AUC0-∞ is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Measured: 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
AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir
AUC0-24 is a measure of total exposure to uprifosbuvir in plasma from dosing to 24 hours following oral administration of MK-3682B.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
Maximum Plasma Concentration (Cmax) of Uprifosbuvir
Cmax is the maximum amount of uprifosbuvir in plasma following oral administration of MK-3682B.
Measured: 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
Plasma Concentration 24 Hours Post-dose (C24) of Uprifosbuvir
C24 is the plasma concentration of uprifosbuvir 24 hours following oral administration of MK-3682B.
Measured: 24 hours post-dose
Time to Reach Maximum Plasma Concentration (Tmax) of Uprifosbuvir
Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir following oral administration of MK-3682B.
Measured: 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
Apparent Total Body Clearance (CL/F) of Uprifosbuvir
CL/F is the apparent total body clearance of uprifosbuvir following oral administration of MK-3682B.
Measured: 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
Apparent Volume of Distribution (Vz/F) of Uprifosbuvir
Vz/F is the apparent volume of distribution of uprifosbuvir following oral administration of MK-3682B.
Measured: 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
Apparent Terminal Half-life in Plasma (t½) of Uprifosbuvir
t1/2 is the amount of time required to clear 50% of uprifosbuvir from plasma following oral administration of MK-3682B.
Measured: 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 of Uprifosbuvir Metabolite M5
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.
Measured: 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-∞ of Uprifosbuvir Metabolite M5
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.
Measured: 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
AUC0-24 of Uprifosbuvir Metabolite M5
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.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
Cmax of Uprifosbuvir Metabolite M5
Cmax is the maximum amount of uprifosbuvir metabolite M5 in plasma following oral administration of MK-3682B.
Measured: 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
C24 of Uprifosbuvir Metabolite M5
C24 is the plasma concentration of uprifosbuvir metabolite M5 24 hours following oral administration of MK-3682B.
Measured: 24 hours post-dose
Tmax of Uprifosbuvir Metabolite M5
Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M5 following oral administration of MK-3682B.
Measured: 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
Lag Time (Tlag) of Uprifosbuvir Metabolite M5
Tlag is the time from dosing to first appearance in plasma of uprifosbuvir metabolite M5 following oral administration of MK-3682B.
Measured: 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
t½ of Uprifosbuvir Metabolite M5
t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M5 from plasma following oral administration of MK-3682B.
Measured: 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 of Uprifosbuvir Metabolite M6
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.
Measured: 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-∞ of Uprifosbuvir Metabolite M6
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.
Measured: 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
AUC0-24 of Uprifosbuvir Metabolite M6
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.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
Cmax of Uprifosbuvir Metabolite M6
Cmax is the maximum amount of uprifosbuvir metabolite M6 in plasma following oral administration of MK-3682B.
Measured: 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
C24 of Uprifosbuvir Metabolite M6
C24 is the plasma concentration of uprifosbuvir metabolite M6 24 hours following oral administration of MK-3682B.
Measured: 24 hours post-dose
Tmax of Uprifosbuvir Metabolite M6
Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M6 following oral administration of MK-3682B.
Measured: 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
t½ of Uprifosbuvir Metabolite M6
t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M6 from plasma following oral administration of MK-3682B.
Measured: 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 of Grazoprevir (MK-5172)
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.
Measured: 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-∞ of Grazoprevir
AUC0-∞ is a measure of total exposure to grazoprevir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Measured: 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
AUC0-24 of Grazoprevir
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.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
Cmax of Grazoprevir
Cmax is the maximum amount of grazoprevir in plasma following oral administration of MK-3682B.
Measured: 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
C24 of Grazoprevir
C24 is the plasma concentration of grazoprevir 24 hours following oral administration of MK-3682B.
Measured: 24 hours post-dose
Tmax of Grazoprevir
Tmax is the time required to reach the maximum post-dose plasma concentration of grazoprevir following oral administration of MK-3682B.
Measured: 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 of Grazoprevir
CL/F is the apparent total body clearance of grazoprevir following oral administration of MK-3682B.
Measured: 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 of Grazoprevir
Vz/F is the apparent volume of distribution of grazoprevir following oral administration of MK-3682B.
Measured: 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
t½ of Grazoprevir
t1/2 is the amount of time required to clear 50% of grazoprevir from plasma following oral administration of MK-3682B.
Measured: 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 of Ruzasvir (MK-8408)
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.
Measured: 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-∞ of Ruzasvir
AUC0-∞ is a measure of total exposure to ruzasvir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Measured: 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
AUC0-24 of Ruzasvir
AUC0-24 is a measure of total exposure to ruzasvir in plasma from dosing to 24 hours following oral administration of MK-3682B.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
Cmax of Ruzasvir
Cmax is the maximum amount of ruzasvir in plasma following oral administration of MK-3682B.
Measured: 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
C24 of Ruzasvir
C24 is the plasma concentration of ruzasvir 24 hours following oral administration of MK-3682B.
Measured: 24 hours post-dose
Tmax of Ruzasvir
Tmax is the time required to reach the maximum post-dose plasma concentration of ruzasvir following oral administration of MK-3682B.
Measured: 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 of Ruzasvir
CL/F is the apparent total body clearance of ruzasvir following oral administration of MK-3682B.
Measured: 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 of Ruzasvir
Vz/F is the apparent volume of distribution of ruzasvir following oral administration of MK-3682B.
Measured: 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
t½ of Ruzasvir
t1/2 is the amount of time required to clear 50% of ruzasvir from plasma following oral administration of MK-3682B.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2016 (estimated)
- Study start19 Jan 2016
- Primary completion26 Aug 2016
- Study completion26 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02661126
- Sponsor's protocol ID
- 3682B-030
- Other IDs
- MK-3682B-030, CA16919
- Status last verified
- Dec 2018
- First submitted
- 19 Jan 2016
- Last updated
- 9 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02661126
- Acronym / sponsor ID
- 3682B-030
- Conditions
- Hepatitis C
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 19 Jan 2016 (actual)
- Primary completion
- 26 Aug 2016 (actual)
- Study completion
- 26 Aug 2016 (actual)
- First posted
- 22 Jan 2016 (estimated)
- Results
- Posted 14 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Moderate RI Participants | Experimental | Drug: MK-3682BParticipants 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. |
| Severe RI Participants | Experimental | Drug: MK-3682BParticipants 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. |
| Healthy Participants | Experimental | Drug: MK-3682BHealthy 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-3682BFDC oral tablet containing 225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir. | Drug | Healthy Participants, Moderate RI Participants, Severe RI Participants |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-3682B in people with Hepatitis C, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 42 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2019.