Safety, Tolerability and Efficacy Study of V117957 in Subjects With Insomnia Associated With Alcohol Cessation
Condition: Insomnia
MeSH terms: Sleep Initiation and Maintenance Disorders
Intervention: V117957 tablets; Placebo
Intervention description: V117957 tablets taken orally at bedtime; Tablets to match V117957
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 114.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the safety, tolerability and efficacy of V117957 in
      subjects with alcohol use disorder (AUD) who experience insomnia associated with alcohol
      cessation, compared to placebo.
    

Eligibility criteria:

        Key Inclusion Criteria include:

          -  Male or female, 18-64 years of age with a body weight of 50-100 kg (110-220 lbs) and a
             body mass index (BMI) of 18-32 kg/m2.

          -  Otherwise healthy as determined by medical evaluation that includes: medical history,
             physical examination, neurological exam, laboratory tests, vital signs, and cardiac
             monitoring.

          -  History of moderate or severe alcohol use disorder (AUD) categorized based on
             Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria,
             as follows:

               -  Moderate as defined by presence of 4-5 of the 11 criteria

               -  Severe as defined by the presence of ≥ 6 of the 11 criteria.

          -  At least 3 weeks and not more than 6 months since last alcoholic beverage intake at
             the time of study screening. Any subject who completed an alcohol detoxification
             program must be at least 7 days from completion of the program at the time of
             screening.

          -  Persistent insomnia that emerged or worsened during AUD period, or during or after
             alcohol cessation characterized by a study-specific sleep diary.

          -  A female participant is eligible to participate if she is not pregnant and not
             breastfeeding. Both females of childbearing potential and nonsurgically sterilized
             males with a sexual partner of childbearing potential must be willing to use adequate
             and reliable contraception throughout the study.

          -  Willing to refrain from a behavioral or other treatment program for insomnia during
             participation in the study.

        Key Exclusion Criteria include:

          -  Current diagnosis of a sleep-related breathing disorder including obstructive sleep
             apnea (with or without continuous positive airway pressure (CPAP) treatment), periodic
             limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder or
             narcolepsy.

          -  An apnea-hypopnea index (AHI) score of >10 or a periodic limb movement arousal index
             (PLMAI) score of > 15 recorded during the screening period PSG.

          -  Documented history of insomnia prior to onset of the alcohol use disorder (AUD), which
             did not worsen during the AUD period or during or after alcohol cessation.

          -  Comorbid conditions which interfere with normal sleep pattern or the evaluation of
             next day residual effects.

          -  Any lifetime history of suicidal ideation or behavior.

          -  History of or any current conditions that might interfere with drug absorption,
             distribution, metabolism, or excretion (including any surgical interventions for
             weight loss).

          -  Any history of seizures (except related to alcohol withdrawal) or head trauma with
             sequelae.

          -  Known history of testing positive for human immunodeficiency virus (HIV), hepatitis B
             surface antigen (HBsAg) or hepatitis C antibody (anti-HCV).

          -  History of diagnosed, active liver disease or elevated liver enzymes/bilirubin.

          -  History of kidney stones or renal insufficiency or abnormal kidney function at
             screening.

          -  Uncontrolled hypertension (> 140 mm Hg systolic / 90 mm Hg diastolic).

          -  Use of any medication that affects sleep and/or wake function during the week before
             starting the screening period.

          -  Subjects currently undergoing treatment of other addictions in addition to alcohol.

          -  Excessive caffeine consumption.

          -  Positive urine drug screen for prohibited substances, except for cannabis on a
             case-by-case basis.

          -  History of drug use disorder over the past year, other than
             alcohol/nicotine/caffeine/cannabis.

          -  Plans to travel across more than 3 time zones in the 2 weeks before screening, or
             during study participation.

          -  Night or rotating shift worker.

          -  Any history and/or current evidence of other medical (eg, cardiac, respiratory,
             gastrointestinal, renal, malignancy other than basal cell carcinoma), neurological, or
             psychiatric conditions that, in the opinion of the investigator, could affect the
             subject's safety or interfere with the study.

        Other protocol-specific inclusion/exclusion criteria may apply.