Pharmacokinetics of Suvorexant in Participants With Hepatic Insufficiency (MK-4305-017)

Insomnia Clinical Trial

Official title:

A Single Dose Study to Investigate the Pharmacokinetics of MK-4305 in Patients With Hepatic Insufficiency

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01043926
• Other study ID #: 4305-017
• Secondary ID: 2010_500
• Status: Completed
• Phase: Phase 1
• Start date: February 22, 2010
• Est. completion date: April 14, 2010

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will determine whether the plasma concentration-time profile and pharmacokinetics (PK) of suvorexant (MK-4305) in participants with moderate and mild hepatic insufficiency are similar to those observed in healthy participants.

Description:

Study Design:

This study plans to enroll 16 participants in Part I (8 participants with moderate hepatic insufficiency and 8 healthy participants) and 16 participants in Part II (8 participants with mild hepatic insufficiency and 8 healthy participants).

Part II will be conducted only if the primary hypothesis is not met and there is a significant difference in the PK of suvorexant between healthy participants and moderate hepatic insufficiency participants in Part I.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 14, 2010
• Est. primary completion date: April 14, 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria for Hepatic Insufficiency Participants:

• Females of reproductive potential must have a negative pregnancy test and agree to use (and/or have their partner use) two acceptable methods of birth control

• Body Mass Index (BMI) =35 kg/m^2 prior to start of study

• Diagnosis of stable hepatic insufficiency

• Smoking is restricted to =10 cigarettes per day

Inclusion Criteria for Healthy Matched Participants:

• Females of reproductive potential must have a negative pregnancy test and agree to use (and/or have their partner use) two acceptable methods of birth control

• BMI within approximately 20% of that of his/her hepatic participant

• Participant is healthy

• Participant is matched by race, gender, age (+/- 5 yrs) to his/her hepatic participant enrolled in the study

• Smoking is restricted to =10 cigarettes per day

Exclusion Criteria for Hepatic Insufficiency Participants:

• Participant is mentally or legally incapacitated

• History of a clinically significant psychiatric disorder over the last 5 to 10 years

• Participant has a history of any illness not related to his/her hepatic insufficiency

• History of a persistent sleep abnormality occurring for at least three (3)

months

• Participant has a history of stroke, chronic seizures, or major neurological disorder

• History of clinically significant hematological, immunological, renal,

respiratory, or genitourinary abnormalities, uncomplicated kidney stones or childhood asthma

• History of cancer

• History of cataplexy

• Participant is a nursing mother

• Participant consumes >3 servings of alcohol a day

• Participant consumes >6 caffeine servings a day

• History of multiple and/or severe allergies

• Participant is currently using or has history of illegal drug use

• Participant has traveled across 3 or more time zones within 2 weeks of study participation

• Participant works a night shift and is not able to avoid night shift work within 1 week before each treatment visit

Exclusion Criteria for Healthy Matched Participants:

• Participant is mentally or legally incapacitated. History of a clinically significant psychiatric disorder over the last 5 to 10 years.

• Participant has a history of any illness

• History of a persistent sleep abnormality occurring for at least three (3) months

• Participant has a history of stroke, chronic seizures, or major neurological disorder

• History of clinically significant endocrine, gastrointestinal,

cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities, uncomplicated kidney stones or childhood asthma

• History of cancer

• History of cataplexy

• Participant is a nursing mother

• Participant consumes >3 servings of alcohol a day

• Participant consumes >6 caffeine servings a day

• History of multiple and/or severe allergies

• Participant is currently using or has history of illegal drug use

• Participant has a history of any chronic and/or active hepatic disease

• Participant has traveled across 3 or more time zones within 2 weeks of study participation

• Participant works a night shift and is not able to avoid night shift work within 1 week before each treatment visit

Related Conditions & MeSH terms

• Hepatic Insufficiency
• Insomnia

Intervention

Drug:
• Suvorexant
single 20 mg dose of suvorexant will be administered as 2 x 10 mg film coated tablets on Day 1 after an overnight fast with water.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-8) After Single Dose Suvorexant: Moderate Hepatic Insufficiency Participants Versus Healthy Participants (Part I)	Overall exposure was assessed by the area under the plasma concentration versus time curve from time zero to infinity (AUC[0-8]). AUC(0-8) was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC[0-last]) and Ct/?, where Ct was the last measurable concentration and ? was the apparent terminal rate constant.	Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
Primary	AUC(0-8) After Single Dose Suvorexant: Mild Hepatic Insufficiency Participants Versus Healthy Participants (Part II)	Overall exposure was assessed by the area under the plasma concentration versus time curve from time zero to infinity (AUC[0-8]). AUC(0-8) was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC[0-last]) and Ct/?, where Ct was the last measurable concentration and ? was the apparent terminal rate constant.	Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
Secondary	Maximum Plasma Concentration (Cmax) of Suvorexant After Single Dose: Moderate Hepatic Insufficiency Participants Versus Healthy Participants	Cmax was defined as the maximum observed concentration of a drug after administration.	Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
Secondary	Number of Participants With an Adverse Event (AE)	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.	From administration of study drug through 14 days after administration of study drug
Secondary	Number of Participants Who Discontinued Study Due to an AE	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.	From administration of study drug through 14 days after administration of study drug