InsomniaPhase 1NCT01043926

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

A Phase 1 study testing Suvorexant in people with Insomnia and Hepatic Insufficiency, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

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. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Insomnia, Hepatic Insufficiency
What is being tested?: Suvorexant
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: No sites listed yet
Study dates: 22 Feb 2010to 14 Apr 2010
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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
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

Show all 9Show fewer

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

Who cannot join

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

Show all 33Show fewer

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
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

About this study

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

Read the 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.

Conditions: Insomnia, Hepatic Insufficiency
Being tested: Suvorexant
Keywords: Hepatic Insufficiency
Medical subject headings: Sleep Initiation and Maintenance Disorders, Hepatic Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SuvorexantDrug
Also called MK-4305
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.

Study groups in NCT01043926
Study group	Role	What they receive
Participants with Moderate Hepatic Insufficiency (Part I)	Experimental	Participants with moderate hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part I of the study. Receives: Drug: Suvorexant
Healthy Participants (Part I)	Experimental	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. Receives: Drug: Suvorexant
Participants with Mild Hepatic Insufficiency (Part II)	Experimental	Participants with mild hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part II of the study (if conducted). Receives: Drug: Suvorexant
Healthy Participants (Part II)	Experimental	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). Receives: Drug: Suvorexant

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
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.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose

Secondary outcomes (3)

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.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, and 144 hours post-dose
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.
Measured: From administration of study drug through 14 days after administration of 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.
Measured: From administration of study drug through 14 days after administration of study drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Feb 201014 Apr 2010

First posted7 Jan 2010 (estimated)
Study start22 Feb 2010
Primary completion14 Apr 2010
Study completion14 Apr 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for InsomniaStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01043926
Sponsor's protocol ID: 4305-017
Other IDs: 2010_500
Status last verified: Aug 2018
First submitted: 5 Jan 2010
Last updated: 21 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Insomnia trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single Dose Study to Investigate the Pharmacokinetics of MK-4305 in Patients With Hepatic Insufficiency
ClinicalTrials.gov ID: NCT01043926
Acronym / sponsor ID: 4305-017
Conditions: Insomnia, Hepatic Insufficiency
Keywords: Hepatic Insufficiency
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 22 Feb 2010 (actual)
Primary completion: 14 Apr 2010 (actual)
Study completion: 14 Apr 2010 (actual)
First posted: 7 Jan 2010 (estimated)
Results: Posted 29 Aug 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study Design:

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Participants with Moderate Hepatic Insufficiency (Part I)	Experimental	Drug: SuvorexantParticipants with moderate hepatic insufficiency will receive a single dose of 20 mg open-label suvorexant during Part I of the study.
Healthy Participants (Part I)	Experimental	Drug: SuvorexantHealthy 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 (Part II)	Experimental	Drug: SuvorexantParticipants 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 (Part II)	Experimental	Drug: SuvorexantHealthy 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).

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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
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

Key exclusion criteria (33 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SuvorexantAlso: MK-4305single 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.	Drug	Healthy Participants (Part I), Healthy Participants (Part II), Participants with Mild Hepatic Insufficiency (Part II), Participants with Moderate Hepatic Insufficiency (Part I)

Primary outcome

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
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
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.

3 secondary outcomes

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
Number of Participants With an Adverse Event (AE)
Time frame: From administration of study drug through 14 days after administration of 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

Results and safety

Results posted to the registry on 29 Aug 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Participants With Moderate Hepatic Insufficiency (Part I)	8	8
Healthy Participants (Part I)	8	8
Participants With Mild Hepatic Insufficiency (Part II)	0	0
Healthy Participants (Part II)	0	0

Primary outcome: 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. Geometric mean (95% Confidence Interval). Unit: μM•hr

Measure	Participants With Moderate Hepatic Insufficiency (Part I) n = 8	Healthy Participants (Part I) n = 8
Value	14.09 (10.48 to 18.93)	13.73 (10.09 to 18.69)

Participants With Moderate Hepatic Insufficiency (Part I) vs Healthy Participants (Part I): AUC(0-∞) Geometric Mean Ratio: 1.03 (90% CI 0.74 to 1.43), ANCOVA

Population analysed: All Treated Participants

Primary outcome: 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

Population analysed: 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.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs were collected from the time of study drug administration up to approximately 14 days post study drug administration.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Participants With Moderate Hepatic Insufficiency (Part I)	0 of 8 (0%)	7 of 8 (87.5%)	Not reported
Healthy Participants (Part I)	0 of 8 (0%)	5 of 8 (62.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Suvorexant in people with Insomnia and Hepatic Insufficiency, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01043926.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2018.