Primary Objective: - to evaluate the pharmacokinetic (PK) parameters (AUC0-t, AUC0-inf, Cmax, C24hr, Tmax, and apparent t*) of MK-3682 and its circulating metabolites (IDX20664 and IDX23267), MK-5172, and MK-8742 following administration of two…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Hypotheses for this study:
- to estimate the pharmacokinetic (PK) parameters (AUC0-t, AUC0-inf, Cmax,
C24hr, Tmax, and apparent t*) of MK-3682 and its circulating metabolites
(IDX20664 and IDX23267), MK-5172, and MK-8742 following administration of two
premarket formulations of a fixed-dose combination of MK-3682A (FDC-A and
FDC-B) 300 mg/100 mg/50 mg relative to the individual components when
co-administered at a dose of 300 mg/100 mg/50 mg.
- to estimate the effects of a high fat meal on the pharmacokinetic (PK)
parameters (AUC0-t, AUC0-inf, Cmax, C24hr, Tmax, and apparent t*) of MK-3682
and its circulating metabolites (IDX20664 and IDX23267), MK-5172, and MK-8742
following administration of two premarket formulations of a fixed-dose
combination of MK-3682A (FDC-A and FDC-B) 300 mg/100 mg/50 mg relative to the
fasted state.
Secondary outcome
Safety
Background summary
Merck is developing an all-oral combination regimen consisting of MK-3682 (HCV
NS5B nucleoside monophosphate prodrug inhibitor), MK-5172 (HCV NS3A protease
inhibitor), and MK-8742 (HCV NS5A inhibitor). MK-3682, MK-5172, and MK-8742,
all with potent activity against several HCV genotypes, are being developed as
an all-oral direct-acting antiviral regimen. The current study should provide
relative bioavailability data to guide pre-market formulation development of an
FDC (fixed-dose combination) for these three antiviral agents which will be
used in Phase III development.
Study objective
Primary Objective:
- to evaluate the pharmacokinetic (PK) parameters (AUC0-t, AUC0-inf, Cmax,
C24hr, Tmax, and apparent t*) of MK-3682 and its circulating metabolites
(IDX20664 and IDX23267), MK-5172, and MK-8742 following administration of two
premarket formulations of a fixed-dose combination of MK-3682A (FDC-A and
FDC-B) relative to the individual components when co-administered at a dose of
300 mg/100 mg/50 mg.
- to evaluate the effects of a high fat meal on the pharmacokinetic (PK)
parameters (AUC0-t, AUC0-inf, Cmax, C24hr, Tmax, and apparent t*) of MK-3682
and its circulating metabolites (IDX20664 and IDX23267), MK-5172, and MK-8742
following administration of two premarket formulations of a fixed-dose
combination of MK-3682A (FDC-A and FDC-B) relative to the fasted state, when
provided at a dose of 300 mg/100 mg/50 mg.
Secondary Objective:
- to evaluate the safety and tolerability of single oral doses of
co-administered MK-3682, MK-5172, and MK-8742.
Study design
Open-Label, Single-Dose, Randomized, Three-Period Crossover Study with a
Fourth, Fixed-Sequence Fed Period (Five Treatments Administered in Four
Periods)
Intervention
Treatment A: Co-administration of 2 x 150 mg MK-3682 tablets, 1 x 100 mg
MK-5172 tablet, and 1 x 50 mg MK-8742 tablet
Administered following an overnight fast of at least 10.5 hours.
Treatment B: 1 x MK-3682A (MK-3682/MK-5172/MK-8742, 300 mg/100 mg/50 mg) FDC-A
Tablet
Administered following an overnight fast of at least 10.5 hours.
Treatment C: 1 x MK-3682A (MK-3682/MK-5172/MK-8742, 300 mg/100 mg/50 mg) FDC-B
Tablet
Administered following an overnight fast of at least 10.5 hours.
Treatment D: 1 x MK-3682A (MK-3682/MK-5172/MK-8742, 300 mg/100 mg/50 mg) FDC-A
Tablet
Treatment E: 1 x MK-3682A (MK-3682/MK-5172/MK-8742, 300 mg/100 mg/50 mg) FDC-B
Tablet
Study burden and risks
For MK-3682, possible adverse events include: dizziness, headache, nausea,
abdominal discomfort, and abnormal feces.
For MK-5172, possible adverse events include: headache, loose stools, abdominal
pain, nausea, abdominal discomfort, and fatigue.
For MK-8742, possible adverse events include: included gastrointestinal
disorders, fatigue; infections, nervous system disorders, dysguesia, and skin
irritation - the most commonly reported adverse event was headache.
The blood collection procedure is not dangerous, but may cause discomfort or
bruising. Occasionally, fainting or an infection at the bloodsampling site can
occur. The effects of the test medication on an unborn child are unknown
East Lincoln Ave 126
Rahway NJ 07065
US
East Lincoln Ave 126
Rahway NJ 07065
US
Listed location countries
Age
Inclusion criteria
1. Non-tobacco using males and non-pregnant females, 18-55 years of age, inclusive.
2. A body mass index (BMI) of 19-32 kg/m² inclusive.
3. Good health as determined by lack of clinically significant abnormalities in health assessments performed at screening.
Exclusion criteria
1. Females who are pregnant, lactating or likely to become pregnant during the study.
2. Significant history or current evidence of chronic infectious disease, system disorders, organ dysfunction, especially cardiovascular disorders.
3. Receipt of any drug as part of a research study within 30 days before initial dosing.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-004907-58-NL |
| CCMO | NL51532.056.14 |