Trial Outcomes & Findings for Pharmacokinetics of Suvorexant in Participants With Hepatic Insufficiency (MK-4305-017) (NCT NCT01043926)
NCT ID: NCT01043926
Last Updated: 2018-09-21
Results Overview
Overall exposure was assessed by the area under the plasma concentration versus time curve from time zero to infinity (AUC\[0-∞\]). AUC(0-∞) was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC\[0-last\]) and Ct/λ, where Ct was the last measurable concentration and λ was the apparent terminal rate constant.
COMPLETED
PHASE1
16 participants
Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
2018-09-21
Participant Flow
16 participants were enrolled in Part I of the study. Because the primary hypothesis was met, no participants were enrolled in Part II of the study.
Participant milestones
| Measure |
Participants With Moderate Hepatic Insufficiency (Part I)
Participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
Healthy Participants (Part I)
Healthy participants matched to participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
Participants With Mild Hepatic Insufficiency (Part II)
Participants with mild hepatic insufficiency were to receive a single dose of 20 mg open-label suvorexant during Part II of the study. No participants were enrolled on this arm.
|
Healthy Participants (Part II)
Healthy participants matched to participants with mild hepatic insufficiency were to receive a single dose of 20 mg open-label suvorexant during Part II of the study. No participants were enrolled on this arm.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
0
|
0
|
|
Overall Study
COMPLETED
|
8
|
8
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics of Suvorexant in Participants With Hepatic Insufficiency (MK-4305-017)
Baseline characteristics by cohort
| Measure |
Participants With Moderate Hepatic Insufficiency (Part I)
n=8 Participants
Participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
Healthy Participants (Part I)
n=8 Participants
Healthy participants matched to participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58 years
STANDARD_DEVIATION 5.1 • n=5 Participants
|
57 years
STANDARD_DEVIATION 4.0 • n=7 Participants
|
57.3 years
STANDARD_DEVIATION 4.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dosePopulation: All Treated Participants
Overall exposure was assessed by the area under the plasma concentration versus time curve from time zero to infinity (AUC\[0-∞\]). AUC(0-∞) was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC\[0-last\]) and Ct/λ, where Ct was the last measurable concentration and λ was the apparent terminal rate constant.
Outcome measures
| Measure |
Participants With Moderate Hepatic Insufficiency (Part I)
n=8 Participants
Participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
Healthy Participants (Part I)
n=8 Participants
Healthy participants matched to participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-∞) After Single Dose Suvorexant: Moderate Hepatic Insufficiency Participants Versus Healthy Participants (Part I)
|
14.09 μM•hr
Interval 10.48 to 18.93
|
13.73 μM•hr
Interval 10.09 to 18.69
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dosePopulation: Per protocol, the decision to perform AUC(0-∞) analysis in mild hepatic insufficiency participants was conditional on results of AUC(0-∞) analysis in moderate hepatic insufficiency participants. Since the primary hypothesis in moderate hepatic insufficiency participants was met, AUC(0-∞) analysis in mild hepatic insufficiency was not done.
Overall exposure was assessed by the area under the plasma concentration versus time curve from time zero to infinity (AUC\[0-∞\]). AUC(0-∞) was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC\[0-last\]) and Ct/λ, where Ct was the last measurable concentration and λ was the apparent terminal rate constant.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dosePopulation: All Treated Participants
Cmax was defined as the maximum observed concentration of a drug after administration.
Outcome measures
| Measure |
Participants With Moderate Hepatic Insufficiency (Part I)
n=8 Participants
Participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
Healthy Participants (Part I)
n=8 Participants
Healthy participants matched to participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Suvorexant After Single Dose: Moderate Hepatic Insufficiency Participants Versus Healthy Participants
|
0.800 μM
Interval 0.603 to 1.062
|
0.854 μM
Interval 0.636 to 1.147
|
SECONDARY outcome
Timeframe: From administration of study drug through 14 days after administration of study drugPopulation: All Treated Participants
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug.
Outcome measures
| Measure |
Participants With Moderate Hepatic Insufficiency (Part I)
n=8 Participants
Participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
Healthy Participants (Part I)
n=8 Participants
Healthy participants matched to participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
|---|---|---|
|
Number of Participants With an Adverse Event (AE)
|
7 participants
|
5 participants
|
SECONDARY outcome
Timeframe: From administration of study drug through 14 days after administration of study drugPopulation: All Treated Participants
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug.
Outcome measures
| Measure |
Participants With Moderate Hepatic Insufficiency (Part I)
n=8 Participants
Participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
Healthy Participants (Part I)
n=8 Participants
Healthy participants matched to participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
|---|---|---|
|
Number of Participants Who Discontinued Study Due to an AE
|
0 participants
|
0 participants
|
Adverse Events
Participants With Moderate Hepatic Insufficiency (Part I)
Healthy Participants (Part I)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Participants With Moderate Hepatic Insufficiency (Part I)
n=8 participants at risk
Participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
Healthy Participants (Part I)
n=8 participants at risk
Healthy participants matched to participants with moderate hepatic insufficiency received a single dose of 20 mg open-label suvorexant.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
1/8 • AEs were collected from the time of study drug administration up to approximately 14 days post study drug administration.
|
0.00%
0/8 • AEs were collected from the time of study drug administration up to approximately 14 days post study drug administration.
|
|
General disorders
Fatigue
|
12.5%
1/8 • AEs were collected from the time of study drug administration up to approximately 14 days post study drug administration.
|
0.00%
0/8 • AEs were collected from the time of study drug administration up to approximately 14 days post study drug administration.
|
|
Nervous system disorders
Somnolence
|
75.0%
6/8 • AEs were collected from the time of study drug administration up to approximately 14 days post study drug administration.
|
62.5%
5/8 • AEs were collected from the time of study drug administration up to approximately 14 days post study drug administration.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
- Publication restrictions are in place
Restriction type: OTHER