Pilot Study of a Combination Drug Product for Treatment of Short-term Insomnia
Condition: Short-term Insomnia
MeSH terms: Sleep Initiation and Maintenance Disorders
Intervention: SM-1; Comparator; Placebo
Intervention description: 3-drug combination product containing 50 mg diphenhydramine, 5 mg zolpidem and 0.5 mg lorazepam; 2-drug combination comprised of 5 mg zolpidem and 0.5 mg lorazepam; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 39.0
Sex: All
Minimum age: 25 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Short-term insomnia; difficulty sleeping; sedative; hypnotic

Summary:

      The purpose of this study is to evaluate the effect of a combination drug product containing
      diphenhydramine, zolpidem and lorazepam on total sleep time. Participants will be adults who
      sometimes have difficulty falling asleep or staying asleep, but who do not have chronic
      insomnia. The study involves 3 one-night stays in a sleep center in New York City.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Body mass index (BMI) between 19 and 32 kg/m2, inclusive;

          -  Report occasional difficulty falling asleep or staying asleep;

          -  Report a regular, habitual bedtime between 21:00 and 24:00, routinely spend at least
             7.5 and no more than 9.0 hours in bed each night and observe a bedtime that does not
             vary by more than 2 hours over the course of the week. Subjects will be required to
             complete at least 5 days of sleep information in a diary provided at the screening
             visit and returned to study personnel no later than 24 hours prior to check-in for the
             first overnight visit.

          -  Be in good general health as determined by a thorough medical history and physical
             examination including vital signs and clinical laboratory tests;

          -  Females of childbearing potential must be using an acceptable method of contraception,
             have a negative serum pregnancy test at screening and have a negative urine pregnancy
             test before randomization and prior to each Treatment Period. Acceptable methods of
             contraception include oral, intrauterine and injectable contraceptives or double
             barrier methods. After screening, subjects using oral contraceptives must agree to add
             a double barrier method until 30 days following the last dose of study medication.
             Female subjects relying on oral contraceptives must have been using them for at least
             one month prior to screening;

          -  Female subjects who have been surgically sterilized are eligible if they have a
             negative serum pregnancy test at screening and negative urine pregnancy test at
             check-in for Visits 2 and 3, or are post-menopausal as defined by the cessation of
             menses for a period of at least 2 years prior to screening or have had a complete
             hysterectomy;

          -  Male subjects must use an acceptable method of contraception during the course of the
             study and for the 30 days following the last dose of study medication. Acceptable
             methods of contraception include:

               1. Abstinence

               2. A condom and one of the following:

             i. Vasectomy for more than 6 months. ii. Female partner who meets one of the following
             conditions:

               1. Uses a spermicidal gel or foam; or

               2. Has had a tubal ligation, hysterectomy or bilateral oophorectomy; or

               3. Is post-menopausal (menopause is defined as over the age of 60 years, or between
                  45 and 60 years being amenorrheic for at least 2 years with plasma follicle
                  stimulating hormone (FSH) level > 30 UI/L); or

          -  Be able to read, understand, and provide written/dated informed consent before
             enrolling in the study and must be willing to comply with all study procedures;

          -  Be willing and able to be confined to the clinical research site for one night in each
             of 3 treatment periods as required by the protocol.

          -  Refrain from alcohol on PSG days;

          -  On the days of check-in for each of the study's two treatment periods, refrain from
             the use of alcohol and from napping, defined as any sleep episode occurring outside of
             the subject's main sleep episode of the day;

          -  Report a recent history of napping of no more than once per week.

          -  An Epworth Sleepiness Scale score ≤8 at screening.

        Exclusion Criteria:

          -  Clinically significant, acute illness within 14 days prior to screening (Visit 1).

          -  Clinically significant, unstable medical illness;

          -  Evidence or history of clinically significant allergic (except for untreated,
             asymptomatic, seasonal allergies at time of dosing), hematological, renal, endocrine,
             pulmonary, gastrointestinal, cardiovascular, hepatic or neurological disease;

          -  History of cancer or diabetes;

          -  A supine blood pressure > 140/90 millimeters mercury (mm/Hg) at screening;

          -  Heart rate > 100 beats per minute (BPM) at screening;

          -  Clinically significant psychiatric illness, including chronic psychiatric illness or
             the history or presence of any Axis I condition;

          -  History or presence of chronic pain;

          -  Lifetime history of seizure disorder or serious head injury;

          -  Clinically significant sleep disorder, including insomnia, sleep apnea, narcolepsy,
             parasomnia, restless leg syndrome or circadian rhythm disorder;

          -  Any condition that may affect drug absorption;

          -  Travel across more than three time zones, an expected change in sleep schedule or
             involvement in night shift work within one month prior to screening or during the
             study period;

          -  Any clinically significant abnormal finding on physical examination, vital signs or
             clinical laboratory tests, as determined by the Investigator;

          -  History of allergies, or known sensitivity, hypersensitivity, or adverse reaction to
             any drug similar to diphenhydramine, zolpidem or lorazepam;

          -  Pregnant or lactating females;

          -  Positive serum pregnancy test at Visit 1 or positive urine pregnancy test at check-in
             for Visit 2 or 3;

          -  Positive urine drug screen at the Visit 1;

          -  Recent history (≤ one year) of alcohol or drug abuse, or current evidence of substance
             dependence or abuse as defined by DSM-V criteria;

          -  Regular consumption of "large amounts" of xanthine-containing substances (i.e., more
             than 500 mg of caffeine per day or equivalent amounts of xanthine-containing
             substances);

          -  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;

          -  Use of more than 10 products containing nicotine per day or routinely smokes during
             sleep period

          -  Discontinuation of smoking or participation in a smoking cessation program within 90
             days of screening;

          -  Any use with the six months prior to screening of restricted concomitant medications
             including prescription hypnotics, antidepressants, anxiolytics, anticonvulsants or
             narcotics;

          -  Use of any prescription drug, OTC medication, grapefruit juice, herbal preparation or
             food supplement, excluding vitamins, acetaminophen or hormonal contraceptives within
             two weeks of randomization;

          -  Use of any investigational drug within 30 days prior to screening or any prior
             exposure to the study drugs diphenhydramine, zolpidem or lorazepam or other drugs of
             the same pharmaceutical classes;

          -  Positive alcohol breathalyzer test at the time of screening or prior to dosing at
             Visit 2, 3 or 4.