Pharmacokinetics of MK-3682B in Participants With Moderat... | NCT02661126

NCT02661126

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
MK-3682B-030	Other Identifier	Merck Protocol Number
CA16919	Other Identifier	Celerion Protocol Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	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.	Drug: MK-3682B

Interventions

Name	Type	Description	Arm Group Labels	Other Names
MK-3682B	Drug	FDC oral tablet containing 225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir.	Healthy Participants Moderate RI Participants Severe RI Participants

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	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.	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.	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.	24 hours post-dose
Time to Reach Maximum Plasma Concentration (Tmax) of Uprifosbuvir

Eligibility Module

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

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

ID	Title	Description
FG000	Moderate RI Participants	Participants with an eGFR of ≥30 mL/min/1.73m^2 to <60 mL/min/1.73m^2 took 2 MK-3682B fixed dose combination (FDC) tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
FG001	Healthy Participants	Healthy participants (creatinine clearance [CLcr] ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Moderate RI Participants	Participants with an eGFR of ≥30 mL/min/1.73m^2 to <60 mL/min/1.73m^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
BG001	Healthy Participants

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous	Healthy participants were matched to moderate RI participants based on age.

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

All participants are included in the analysis.

Posted

Geometric Mean

95% Confidence Interval

uM*hr

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

ID	Title	Description
OG000	Moderate RI Participants	Participants with an eGFR of ≥30 mL/min/1.73m^2 to <60 mL/min/1.73m^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Moderate RI Participants	Participants with an eGFR of ≥30 mL/min/1.73m^2 to <60 mL/min/1.73m^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D006525	Hepatitis, Viral, Human