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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01043926
First received: January 5, 2010
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Insomnia
Hepatic Insufficiency
Drug: Suvorexant
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Dose Study to Investigate the Pharmacokinetics of MK-4305 in Patients With Hepatic Insufficiency

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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) [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose ] [ Designated as safety issue: No ]
    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.

  • AUC(0-∞) After Single Dose Suvorexant: Mild Hepatic Insufficiency Participants Versus Healthy Participants (Part II) [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Maximum Plasma Concentration (Cmax) of Suvorexant After Single Dose: Moderate Hepatic Insufficiency Participants Versus Healthy Participants [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose ] [ Designated as safety issue: No ]
    Cmax was defined as the maximum observed concentration of a drug after administration.

  • Number of Participants With an Adverse Event (AE) [ Time Frame: From administration of study drug through 14 days after administration of study drug ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Who Discontinued Study Due to an AE [ Time Frame: From administration of study drug through 14 days after administration of study drug ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 16
Study Start Date: February 2010
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Participants with Moderate Hepatic Insufficiency (Part I)
Participants with moderate hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part I of the study.
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.
Other Name: MK-4305
Experimental: Healthy Participants (Part I)
Healthy participants matched to participants with moderate hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part I of the study.
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.
Other Name: MK-4305
Experimental: Participants with Mild Hepatic Insufficiency (Part II)
Participants with mild hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part II of the study (if conducted).
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.
Other Name: MK-4305
Experimental: Healthy Participants (Part II)
Healthy participants matched to participants with mild hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part II of the study (if conducted).
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.
Other Name: MK-4305

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01043926

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01043926     History of Changes
Other Study ID Numbers: 4305-017, 2010_500
Study First Received: January 5, 2010
Results First Received: August 19, 2014
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Hepatic Insufficiency

Additional relevant MeSH terms:
Hepatic Insufficiency
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on November 25, 2014