SM-1 vs 2 Comparators and Placebo in Participants With a History of Transient Insomnia.
Condition: Transient Insomnia
MeSH terms: Sleep Initiation and Maintenance Disorders
Intervention: SM-1; D+Z; D+L; Placebo
Intervention description: 3-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam.; 2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem.; 2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam.; Identical in appearance to SM-1, D+Z and D+L and has the same excipients, but no diphenhydramine, zolpidem, lorazepam or delayed-release coating materials.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Insomnia; Transient Insomnia; Sleep initiation and maintenance disorder

Summary:

      The purpose of this study is to investigate the effectiveness, safety and tolerability of a
      combination drug product (SM-1) containing diphenhydramine, zolpidem and lorazepam, in adult
      participants who sometimes have difficulty in falling asleep or staying asleep, but who do
      not have chronic insomnia. Participants will receive SM-1, or a combination of
      diphenhydramine and zolpidem, or a combination of diphenhydramine and lorazepam, or placebo
      during 4 one-night stays at a sleep center.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed written consent form.

          -  Experienced at least 1 prior episode of transient insomnia meeting all of the
             following criteria: difficulty falling asleep or staying asleep; next day impairment
             or distress associated with the disturbed sleep; frequency of 1 to 7 nights per week;
             duration of less than 1 month or more than 1 month of intermittent episodes.

          -  Routinely spends 6.5 - 9.5 hours in bed each night, with bed time varying no more than
             2 hours over a week. Potential participants will be required to complete a paper diary
             for a minimum of 7 days during the screening period, with at least 5 entries completed
             over the 7 days.

          -  Body Mass Index (BMI) between 19 and 32 kg/m2.

          -  Good general health, as determined by a thorough medical, sleep and psychiatric
             history review, brief physical examination including vital sign measurements, and an
             assessment of screening laboratory test results.

          -  Female subjects of childbearing potential must be using an acceptable method of
             contraception during the study and for the 30 days following the last dose of study
             drug, and must have a negative urine pregnancy test at every study visit. Female
             subjects of non-childbearing potential are not required to use contraception if they
             have been surgically sterilized or are post-menopausal as defined by the cessation of
             menses for a period of at least 2 years before screening.

          -  Male subjects must use an acceptable method of contraception during the study and for
             the 30 days following the last dose of study drug.

          -  Willing and able to be confined to the study center for 1 night in each of 4 treatment
             periods, as required by the protocol.

          -  Refrains from the use of alcohol within 24 hours of check-in for each of 4 treatment
             periods involving an overnight stay at the study center.

          -  Refrains from napping (any sleep episode occurring outside subject's main sleep
             episode) on days of check-in for each of 4 treatment periods involving an overnight
             stay at the study center.

        Exclusion Criteria:

          -  Females who are pregnant, breast-feeding, or planning a pregnancy during the study
             period.

          -  Clinically significant medical disorder or currently unstable medical condition that,
             in the opinion of the investigator, would confound the results of the study.

          -  Abnormal laboratory value at screening, judged clinically significant by the
             investigator.

          -  History or current evidence of severe hepatic (liver) impairment.

          -  Clinically significant psychiatric illness, or the history or presence of a major
             psychiatric illness in the past year.

          -  Clinically significant abnormal finding on physical examination, as determined by the
             investigator.

          -  Lifetime history of seizure disorder (other than childhood febrile seizures) or
             serious head injury.

          -  History of chronic insomnia or other sleep disorders, such as sleep apnea, narcolepsy,
             parasomnia, restless leg syndrome, or circadian rhythm disorder.

          -  Air travel across more than 2 time zones, an expected change in sleep schedule, or
             involvement in night work or shift work within 1 month before screening or during the
             study period.

          -  Reports a recent history of napping of more than once per week.

          -  History of alcohol or substance use disorder within the year before screening, or
             current evidence of alcohol or substance use disorder.

          -  Self-report of a usual consumption of more than 14 units of alcohol per week. One unit
             of alcohol is equivalent to 12 ounces of beer, 4 ounces of wine, or 1 ounce of liquor.

          -  Regular consumption of more than 500 mg of caffeine per day.

          -  History of routinely smoking during sleep period.

          -  Discontinuation of smoking or participation in a smoking cessation program within 30
             days of screening or plans to discontinue smoking during the study.

          -  Positive urine drug screen at screening.

          -  Positive alcohol breathalyzer test at any visit.

          -  History of allergy or known sensitivity, hypersensitivity, or adverse reaction to
             diphenhydramine, zolpidem, or lorazepam or other drugs of the same pharmaceutical
             classes.

          -  Use of any medication which affects sleep-wake function within 5 half-lives or 2
             weeks, whichever is longer, before screening until study completion. This includes
             prescription, over-the-counter (OTC), and herbal (e.g. valerian root, melatonin)
             medications.

          -  Use of any investigational drug within 30 days or 5 half-lives, whichever is longer,
             before screening.

          -  Planned surgery (inpatient or outpatient) during the study period.

          -  Employee or family member of the investigator or study center personnel.