Primary ObjectiveTo evaluate and compare the pharmacokinetic (PK) parameters (AUC0-t, AUC0-inf, Cmax, C24hr, Tmax, and apparent t*) of MK-3682 and its circulating metabolites MK-5172, and MK-8742 following administration of three test premarket…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Hypothesis (Estimation):
To estimate the comparative bioavailability of each of the three test PMFs of
an FDC of MK-3682A (FDC-F, FDC-G, and FDC-H) relative to the reference PMF of
MK-3682A FDC (FDC-E) following single-dose administration.
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
a fixed-dose combination (FDC) to provide an all-oral direct-acting antiviral
regimen. The current study will provide relative bioavailability (BA) data to
guide premarket formulation (PMF) development of an MK-3682A FDC which will be
used in Phases 2 and 3. Tablets with different dissolution profiles will be
screened; dissolution profiles will be spaced to result in different F2
(similarity factor) values. The information obtained from this study will be
used to (1) set tablet manufacturing compression targets broadly; (2) validate
the existing process window; and (3) inform time points for setting in vitro
dissolution method specifications.
Study objective
Primary Objective
To evaluate and compare the pharmacokinetic (PK) parameters (AUC0-t, AUC0-inf,
Cmax, C24hr, Tmax, and apparent t*) of MK-3682 and its circulating metabolites
MK-5172, and MK-8742 following administration of three test premarket
formulations (PMFs) of a fixed-dose
combination (FDC) of MK-3682A (FDC-F, FDC-G, and FDC-H), each manufactured to
obtain different dissolution properties versus a reference PMF of MK-3682A FDC
(FDC-E). Hypothesis (Estimation): To estimate the comparative bioavailability
of each of the three test PMFs of an FDC of MK-3682A (FDC-F, FDC-G, and FDC-H)
relative to the reference PMF of MK-3682A FDC (FDC-E) following single-dose
administration.
Secondary Objective
To evaluate the safety and tolerability of single oral doses of MK-3682,
MK-5172, and MK-8742, administered as an FDC tablet.
Study design
This is an open-label, single-dose, randomized, four-treatment, four-period,
foursequence, crossover study in 16 non-tobacco using, healthy adult male and
female subjects.
Intervention
The subjects will receive the study drugs, under direct observation, on Day 1
of each period according to the four-treatment, four-period,
four-sequence randomization schedule. Each treatment will be administered to
subjects following an overnight fast of at least 10
hours. All doses will be administered with 240 mL of room temperature water.
Treatment 1 (Reference): 1 x MK-3682A (MK-3682/MK-5172/MK-8742, 225 mg/50 mg/25
mg) FDC-E Tablet
Treatment 2 (Test): 1 x MK-3682A (MK-3682/MK-5172/MK-8742, 225 mg/50 mg/25 mg)
FDC-F Tablet
Treatment 3 (Test): 1 x MK-3682A (MK-3682/MK-5172/MK-8742, 225 mg/50 mg/25 mg)
FDC-G Tablet
Treatment 4 (Test): 1 x MK-3682A (MK-3682/MK-5172/MK-8742, 225 mg/50 mg/25 mg)
FDC-H Tablet
Study burden and risks
For MK-3682, possible adverse events include: dizziness, headache, nauseam
abdominal discomfort, and abnormal feces
For MK-5172, possible adverse events include: headache, loose stools, abdominal
pain, nausea, abdmonial discomfort and fatigue
For MK-8742, possible adverse events include: gastrointestinal disorders,
fatique, 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 was unknown.
East Lincoln Avenue 126
Rahway NJ 07065
US
East Lincoln Avenue 126
Rahway NJ 07065
US
Listed location countries
Age
Inclusion criteria
1. Non-tobacco using males and females, 18-55 years of age, inclusive.
2. A body mass index (BMI) of 19-32 kg/m² inclusive as calculated according to QPS Netherlands B.V. Standard Operating Procedures.
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 intend to become pregnant during the study.
2. History of allergy or sensitivity to MK-3682, MK-5172, or MK-8742 or history of any drug hypersensitivity or intolerance which, in the opinion of the Investigator, would compromise the safety of the subject or the integrity of study.
3. Significant history or current evidence of chronic infectious disease, system disorders, organ dysfunction, especially cardiovascular disorders (angina, heart failure, irregular heartbeats, heart attack, hypertension, hypotension), stroke, renal or hepatic disorder, diabetes or bleeding
4. 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 | EUCTR2015-002023-26-NL |
| CCMO | NL53636.056.15 |