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

Primary Purpose

Insomnia, Hepatic Insufficiency

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Suvorexant
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Insomnia focused on measuring Hepatic Insufficiency

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Participants with Moderate Hepatic Insufficiency (Part I)

    Healthy Participants (Part I)

    Participants with Mild Hepatic Insufficiency (Part II)

    Healthy Participants (Part II)

    Arm Description

    Participants with moderate hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part I of the study.

    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.

    Participants with mild hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part II of the study (if conducted).

    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).

    Outcomes

    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)
    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)
    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
    Cmax was defined as the maximum observed concentration of a drug after administration.
    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.
    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.

    Full Information

    First Posted
    January 5, 2010
    Last Updated
    August 21, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01043926
    Brief Title
    Pharmacokinetics of Suvorexant in Participants With Hepatic Insufficiency (MK-4305-017)
    Official Title
    A Single Dose Study to Investigate the Pharmacokinetics of MK-4305 in Patients With Hepatic Insufficiency
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    February 22, 2010 (Actual)
    Primary Completion Date
    April 14, 2010 (Actual)
    Study Completion Date
    April 14, 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Insomnia, Hepatic Insufficiency
    Keywords
    Hepatic Insufficiency

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    16 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Participants with Moderate Hepatic Insufficiency (Part I)
    Arm Type
    Experimental
    Arm Description
    Participants with moderate hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part I of the study.
    Arm Title
    Healthy Participants (Part I)
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Participants with Mild Hepatic Insufficiency (Part II)
    Arm Type
    Experimental
    Arm Description
    Participants with mild hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part II of the study (if conducted).
    Arm Title
    Healthy Participants (Part II)
    Arm Type
    Experimental
    Arm Description
    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).
    Intervention Type
    Drug
    Intervention Name(s)
    Suvorexant
    Other Intervention Name(s)
    MK-4305
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    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)
    Description
    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.
    Time Frame
    Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
    Title
    AUC(0-∞) After Single Dose Suvorexant: Mild Hepatic Insufficiency Participants Versus Healthy Participants (Part II)
    Description
    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.
    Time Frame
    Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
    Secondary Outcome Measure Information:
    Title
    Maximum Plasma Concentration (Cmax) of Suvorexant After Single Dose: Moderate Hepatic Insufficiency Participants Versus Healthy Participants
    Description
    Cmax was defined as the maximum observed concentration of a drug after administration.
    Time Frame
    Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
    Title
    Number of Participants With an Adverse Event (AE)
    Description
    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.
    Time Frame
    From administration of study drug through 14 days after administration of study drug
    Title
    Number of Participants Who Discontinued Study Due to an AE
    Description
    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.
    Time Frame
    From administration of study drug through 14 days after administration of study drug

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Monitor
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Available IPD and Supporting Information:
    Available IPD/Information Type
    CSR Synopsis
    Available IPD/Information URL
    http://www.merck.com/clinical-trials/study.html?id=4305-017&kw=4305-017&tab=access

    Learn more about this trial

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

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