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Safety and Efficacy Study of Suvorexant in Participants With Primary Insomnia - Study A (MK-4305-028)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01097616
First received: March 26, 2010
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

This is a multicenter study to test the hypothesis that suvorexant (MK-4305) is superior to placebo in improving insomnia as measured by change from baseline in: subjective total sleep time and time to sleep onset, wake time after persistent sleep onset, and latency to onset of persistent sleep. Participants who complete the initial 3-month Treatment (TRT) Phase may participate in an optional 3-month Extension (EXT) Phase.


Condition Intervention Phase
Primary Insomnia
Drug: Suvorexant High Dose (HD)
Drug: Suvorexant Low Dose (LD)
Drug: Comparator: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of MK-4305 in Patients With Primary Insomnia - Study A

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Total Sleep Time (sTSTm) at Month 1 [ Time Frame: Baseline and Month 1 ] [ Designated as safety issue: No ]
    sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily electronic diary (e-diary). Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any polysomnography [PSG] nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  • Suvorexant HD Versus Placebo: Change From Baseline in sTSTm at Month 3 [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
    sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  • Suvorexant HD Versus Placebo: Change From Baseline in Wakefulness After Persistent Sleep Onset (WASO) at Month 1 [ Time Frame: Baseline and Month 1 ] [ Designated as safety issue: No ]
    WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  • Suvorexant HD Versus Placebo: Change From Baseline in WASO at Month 3 [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
    WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  • Suvorexant HD Versus Placebo: Change From Baseline in Mean Subjective Time to Sleep Onset (sTSOm) at Month 1 [ Time Frame: Baseline and Month 1 ] [ Designated as safety issue: No ]
    sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  • Suvorexant HD Versus Placebo: Change From Baseline in sTSOm at Month 3 [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
    sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  • Suvorexant HD Versus Placebo: Change From Baseline in Latency to Onset of Persistent Sleep (LPS) at Month 1 [ Time Frame: Baseline and Month 1 ] [ Designated as safety issue: No ]
    LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment ("Lights-Off") to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  • Suvorexant HD Versus Placebo: Change From Baseline in LPS at Month 3 [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
    LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment ("Lights-Off") to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  • Number of Participants With an Adverse Event (AE) During Initial 3-Month DB TRT Phase [ Time Frame: Up to 3 months ] [ 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. Participants with an AE occurring during the initial 3-month DB TRT Phase are counted once in this summary.

  • Number of Participants Who Discontinued Study Drug Due to an AE Occurring During Initial 3-Month DB TRT Phase [ Time Frame: Up to 3 months ] [ 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. Participants who discontinued study drug treatment due to an AE occurring during the initial 3-month DB TRT Phase are counted once in this summary.


Secondary Outcome Measures:
  • Suvorexant LD/HD Versus Placebo: Change From Baseline in sTSTm at Week 1 [ Time Frame: Baseline and Week 1 ] [ Designated as safety issue: No ]
    sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Week 1 range is Days 2-8 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  • Suvorexant LD Versus Placebo: Change From Baseline in sTSTm at Month 1 [ Time Frame: Baseline and Month 1 ] [ Designated as safety issue: No ]
    sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  • Suvorexant LD Versus Placebo: Change From Baseline in sTSTm at Month 3 [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
    sTSTm is the average over a defined day range of the participant's report of the total amount of time spent asleep before waking for the day, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  • Suvorexant LD/HD Versus Placebo: Change From Baseline in WASO at Night 1 [ Time Frame: Baseline and Night 1 ] [ Designated as safety issue: No ]
    WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  • Suvorexant LD Versus Placebo: Change From Baseline in WASO at Month 1 [ Time Frame: Baseline and Month 1 ] [ Designated as safety issue: No ]
    WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  • Suvorexant LD Versus Placebo: Change From Baseline in WASO at Month 3 [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
    WASO is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  • Suvorexant LD/HD Versus Placebo: Change From Baseline in sTSOm at Week 1 [ Time Frame: Baseline and Week 1 ] [ Designated as safety issue: No ]
    sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Week 1 range is Days 2-8 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  • Suvorexant LD Versus Placebo: Change From Baseline in sTSOm at Month 1 [ Time Frame: Baseline and Month 1 ] [ Designated as safety issue: No ]
    sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 1 range is Days 23-30 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  • Suvorexant LD Versus Placebo: Change From Baseline in sTSOm at Month 3 [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
    sTSOm is the average over a defined day range of the participant's report of the duration of time that it took to fall asleep, as recorded in a daily e-diary. Averages were derived by taking the mean of all available daily measurements (excluding the mornings following any PSG nights) falling within the day range; Month 3 range is Days 76-90 (Day 1 is day of first double-blind dose). A participant must have at least 3 days of data during the defined day range to calculate an average for the day range; otherwise, the mean value was considered missing for that day range. The baseline value is the mean of the last 7 daily measurements obtained during the placebo Run-in period.

  • Suvorexant LD/HD Versus Placebo: Change From Baseline in LPS at Night 1 [ Time Frame: Baseline and Night 1 ] [ Designated as safety issue: No ]
    LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment ("Lights-Off") to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  • Suvorexant LD Versus Placebo: Change From Baseline in LPS at Month 1 [ Time Frame: Baseline and Month 1 ] [ Designated as safety issue: No ]
    LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment ("Lights-Off") to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.

  • Suvorexant LD Versus Placebo: Change From Baseline in LPS at Month 3 [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
    LPS is measured during overnight sleep laboratory (PSG) assessments at baseline, Night 1, Month 1 and Month 3, and is defined as the duration of time from the beginning of PSG assessment ("Lights-Off") to the first interval of 10 consecutive minutes of sleep. Beginning of PSG assessment ("Lights-Off") is at approximately the participant's habitual bedtime. The participant is awakened, or allowed to get out of bed if already awake, after 8 hours of PSG recording ("Lights-On"). PSG assessments consist of electronic measurement of brain activity and eye and muscle movements. PSG data was scored by a Centralized PSG reading center.


Enrollment: 1023
Study Start Date: May 2010
Study Completion Date: December 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Suvorexant HD
Drug
Drug: Suvorexant High Dose (HD)
Suvorexant 40 mg + placebo matching suvorexant 20 mg for participants <65 years old; Suvorexant 30 mg + placebo matching suvorexant 15 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Participants receive this dose during the 3-month TRT Phase and, if applicable, the optional 3-month EXT Phase. During the 1-week double-blind (DB) Run-out (RO) following the TRT/EXT phase, participants in this study arm receive the noted suvorexant dose or placebo, in a 1:1 ratio. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.
Other Name: MK-4305
Experimental: Suvorexant LD
Drug
Drug: Suvorexant Low Dose (LD)
Suvorexant 20 mg + placebo matching suvorexant 40 mg for participants <65 years old; Suvorexant 15 mg + placebo matching suvorexant 30 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Participants receive this dose during the 3-month TRT Phase and, if applicable, the optional 3-month EXT Phase. During the 1-week DB RO following the TRT/EXT phase, participants in this study arm receive the noted suvorexant dose or placebo, in a 1:1 ratio. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.
Other Name: MK-4305
Placebo Comparator: Placebo
Placebo Comparator
Drug: Comparator: Placebo
Matching placebos to suvorexant 40 mg and 20 mg for participants <65 years old; matching placebos to suvorexant 30 mg and 15 mg for participants ≥65 years old; all study drug is tablet for oral administration, taken once daily at bedtime. Placebo is a third treatment arm for comparison to the two active (suvorexant) treatment arms during the 3-month TRT Phase and, if applicable, the optional 3-month EXT Phase. During the 1-week DB RO following the TRT/EXT phase, participants in this study arm continue to receive placebo. During the 2-week single-blind Run-in period prior to randomization all participants receive placebo to suvorexant once daily at bedtime.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be ≥18 yrs old on the day of signing informed consent
  • Diagnosed with Primary Insomnia
  • Good physical and mental health
  • Participant ≥65 yrs old score at least 25 on the Mini Mental State Examination
  • A female participant who is of reproductive potential has a negative serum pregnancy test and agrees to use contraception
  • Reports difficulty with initiating and maintaining sleep during the 4 weeks prior to Visit 1 (accordingly to specific protocol criteria)
  • Reports spending 6.5 to 9 hours nightly in bed on at least 3 out of 7 nights prior to Visit 1
  • Regular bedtime is between 9 pm-1 am
  • Willing to refrain from napping while in study
  • Able to read, understand and complete questionnaires and all diaries
  • Willing to limit alcohol, caffeine, and nicotine consumption while in the study
  • For a portion of participants: Must be willing to stay overnight in a sleep laboratory and must be willing to stay in bed for at least 8 hours each night while at the sleep laboratory

Exclusion Criteria:

  • Female participant is pregnant and/or breastfeeding at Prestudy visit, or expecting to conceive while in study
  • History or diagnosis of another sleep disorder
  • Difficulty sleeping due to a medical condition
  • History of a neurological disorder
  • History of bipolar disorder, psychotic disorder, or posttraumatic stress disorder, or current psychiatric disorder that requires a prohibited medication
  • Ongoing depression
  • History of substance abuse or dependence
  • History or current evidence of a clinically significant cardiovascular disorder or clinically significant electrocardiogram (ECG) at Prestudy Visit
  • Taking certain prohibited medications
  • Consumption of the equivalent of >15 cigarettes a day
  • History of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
  • Participant is considered morbidly obese
  • Previously randomized in another investigational study of suvorexant
  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: NCT01097616

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: NCT01097616     History of Changes
Other Study ID Numbers: 4305-028, 2010_520
Study First Received: March 26, 2010
Results First Received: August 19, 2014
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sleep Initiation and Maintenance Disorders
Dyssomnias
Mental Disorders
Nervous System Diseases
Sleep Disorders
Sleep Disorders, Intrinsic

ClinicalTrials.gov processed this record on November 24, 2014