Clinical trial NCT04035200: Safety, Tolerability and Efficacy Study of V117957 in Subjects With Insomnia Associated With Alcohol Cessation
Official title: A Phase 2, Randomized, Double-Blind, Multi-Center, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety, Tolerability, and Efficacy of V117957 in Subjects With an Alcohol Use Disorder Who Are Experiencing Insomnia Associated With Alcohol Cessation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Insomnia
Lead sponsor: Imbrium Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Purdue Pharma LP
First posted: 2019-07-29
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change From Baseline of Wakefulness After Sleep Onset (WASO) Measured by Polysomnography (PSG)
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
Secondary outcomes:
measure: Change From Baseline in Mean Sleep Efficiency (SE)
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
measure: Change From Baseline in Mean Latency to Persistent Sleep (LPS)
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
measure: Change From Baseline in Mean Total Sleep Time (TST)
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
measure: Change From Baseline in Mean Number of Awakenings (NAW)
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
measure: Change From Baseline in Subjective Sleep Quality (sSleep)
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
measure: Change From Baseline in Subjective Total Sleep Time (sTST)
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
measure: Change From Baseline in Subjective Wakefulness After Sleep Onset (sWASO)
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
measure: Change From Baseline in Subjective Sleep Onset Latency (sSOL)
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
measure: Change From Baseline in Subjective Sleep Efficiency (sSE)
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
measure: Change From Baseline in Subjective Number of Awakenings (sNAW)
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
measure: Change From Baseline in Subjective Morning Sleepiness on Awakening
timeFrame: Baseline, Nights 1 / 2, Nights 20 / 21
measure: Proportion of Responders to V117957 1 mg and 2 mg Compared to Placebo
timeFrame: Nights 1 / 2, Nights 20 / 21
measure: Occurrence of Rebound Insomnia During the Washout/Follow-up Period
timeFrame: Baseline Compared to Washout/Follow-up Period (Nights 22 / 23)
measure: Next Day Residual Effects as Determined by Digit Symbol Substitution Test (DSST).
timeFrame: Baseline, Night 2, Night 21
measure: Next Day Residual Effects as Determined by Karolinska Sleepiness Scale (KSS)
timeFrame: Baseline, Night 2 (9- and 10-hours postdose), Night 21 (9- and 10-hours postdose)
measure: Next Day Residual Effects as Determined by Profile of Mood States (POMS) - Brief
timeFrame: Baseline, Night 2, Night 21
Other outcomes:
Locations:
city: Glendale
country: United States
facility: California Clinical Trials Medical Group
state: California
city: Riverside
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Santa Ana
country: United States
facility: CITrials
state: California
city: Santa Ana
country: United States
facility: SDS Clinical Trials, Inc.
state: California
city: Clearwater
country: United States
facility: St. Francis Medical Institute
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Miami Lakes
country: United States
facility: Innovative Clinical Research, Inc.
state: Florida
city: Miami
country: United States
facility: Research Centers of America, LLC
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research Inc
state: Georgia
city: Chevy Chase
country: United States
facility: Investigational Site
state: Maryland
city: Glen Burnie
country: United States
facility: Sleep Disorders Centers of the Mid Atlantic
state: Maryland
city: Las Vegas
country: United States
facility: Wake Research - Clinical Research Center of Nevada, LLC
state: Nevada
city: Brooklyn
country: United States
facility: SPRI Clinical Trials
state: New York
city: New York
country: United States
facility: Clinilabs Drug Development Corporation
state: New York
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Georgetown
country: United States
facility: Advanced Medical Trials
state: Texas
Study officials:
References: