A Trial Evaluating Pitolisant (BF2.649) in Alcohol Use Disorder Treatment

NCT02800083 | Withdrawn Phase 2 DMC

• 1 other identifier: P15-14/BF2.649
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

• The study primary end point is the decrease in the number of monthly heavy drinking days (HDD) (≥ 60 g/day in men and ≥ 40 g/d in women) from baseline to the end of the double blind Randomized Treatment (RT).
• The Secondary end points will be designed to assess safety and tolerability and to further investigate the effect of pitolisant on other alcohol use criteria (e.g. total alcohol consumption, number of abstinence days), craving as well as the improvement in mental health (depression, sleep) and quality of life.
• Total alcohol consumption (TAC) from baseline to end of treatment. TAC was defined as mean daily alcohol consumption in g/day over a month (28 days).
• Percent of patients without HDDs during the 24 weeks RT phase of the study. (Continuous Controlled Drinking=CCD)
• Percent of Abstinent Days during RT phase (PAD)
• Continuous Abstinence Duration from baseline during 24 weeks RT phase (CAD)
• 4-week point prevalence abstinence at end of treatment
• Improvement in alcohol biomarkers (e.g. ALAT, ASAT, % CDT) during 24 week RT phase
• Craving (Obsessive Compulsive Drinking Scale) during 24 week RT phase
• Beck Depression Inventory (BDI) during 24 week RT phase
• Quality of sleep (Pittsburgh Sleep Quality Index) during RT phase.
• Treatment retention during 24 week RT
• Quality of life (SF-12) during RT phase
• Percent patients without HDDs during the OL follow up period
• Quality of life (SF-12) during OL phase
• Quality of sleep (Pittsburgh Sleep Quality Index) during OL phase
• Treatment retention OL phase Safety will be assessed by evaluation of treatment emergent adverse events (TEAE), physical examinations, clinical laboratory tests (blood chemistry, hematology, and urinalysis), subsequent end of treatment potential withdrawal, evaluation scales and physical examination, measurement of heart rate, blood pressure, and body weight at each study visit )V0-FU5). If at ECG Fridericia's corrected QT interval ≥ 500 ms or if difference to baseline is ≥ 60 ms it will be required to check ECG by second measurement after lying down 10 minutes.

Conditions

Alcohol Abuse, Nervous System

Outcome Measures

Primary Outcomes (1)

• Monthly Heavy Drinking Days (HDD/month)

  Change from Baseline of Monthly Heavy Drinking Days and at week 24

Secondary Outcomes (9)

• Total daily Alcohol Consumption (TAC)

  at week 24 versus Baseline

• Percent of Abstinent Days during 24 weeks medication phase (PAD)

  at week 24 versus Baseline

• Improvement in alcohol biomarkers (ALAT, ASAT, % CDT)

  at baseline , at week 4 , at week 8, at week 12, at week 16, at week 20 and at week 24. versus Baseline

• Continuous Abstinence Duration during 24 weeks medication phase (CAD)

  at week 24 versus Baseline

• Obsessive Compulsive Drinking Scale (OCDC)

  at week 24 versus Baseline

Study Arms (2)

Pitolisant (BF2.649)

EXPERIMENTAL

Histamine H3 receptor H3R antagonist/ inverse agonist

Drug: Pitolisant (BF2.649)

Placebo

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

Pitolisant (BF2.649) DRUG

Pitolisant (BF2.649)

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female with moderate or severe DSM-5 alcohol use disorder (based on the alcohol use disorders section of the MINI Plus)
• Ages 18-65.
• Low to moderate alcohol withdrawal symptoms: CIWA-Ar scale \<10 at baseline assessment
• Normal weight: 18 kg/m2 ≤ BMI ≤ 35 kg/m2.
• Excessive alcohol use: number of heavy drinking days (≥ 60 g/day in men and ≥ 40 g/d in women) ≥15 during 30 days prior to screening and ≥7 during the 2 weeks between screening and baseline.
• Treatment-seeking, treatment goal: reduced drinking or abstinence
• If fertile, both males and females must agree to use effective birth control. Females of child-bearing potential must use a medically accepted effective method of birth control, agree to continue this method for the duration of the study and be negative to serum pregnancy test performed at the screening visit. Females should not be breast-feeding.
• Adequate social support according to the investigator to comply with the study requirements described in the protocol (e.g. transportation to and from trial site, self-rating scales, drug compliance, scheduled visits, etc.).
• Voluntarily expressed willingness to participate in the study, understanding protocol procedures and having signed and dated an informed consent prior to the start of protocol required procedures while not intoxicated (BAC\<0.05).
• Willing to receive psychosocial support

You may not qualify if:

• History of delirium tremens, epilepsy, or withdrawal seizures
• Clinical depression or suicidality: Beck Depression Inventory (BDI) \< 16 and suicidality (Item G =0)
• Recent illicit drug use, i.e. cannabis, cocaine, amphetamines or opioids.
• Clinically significant cardiovascular, hematologic, severe hepatic impairment or (FLTs\> 3 ULN), renal (Stage 2 and 3 according to international classification of renal kidney disease), neurological, endocrinological abnormalities or abnormal clinical laboratory results (in most cases \> 3ULN).
• History of serious head trauma or injury causing loss of consciousness that lasted more than 3 minutes.
• HIV positive; HCV positive; HBsAg positive
• History of psychosis, or current severe psychiatric disorder, e.g. schizophrenia, bipolar disorder, severe depression or organic brain syndrome unrelated to alcohol abuse
• Physical dependence on sedatives or hypnotics that requires pharmacologically supported detox.
• Receiving ongoing alcohol use disorder medication (e.g. Baclofen)
• Other active clinically significant illness, which could interfere with the study conduct or counter-indicate the study treatments or place the patient at risk during the trial or compromise the study participation.
• Known history of syncope, arrhythmia, myocardial infarction or any known significant ECG abnormality
• Known hypersensitivity to the tested treatment including active substance and excipients.
• Participation in clinical trial and receipt of investigational drug(s) during previous 60 days, except as explicitly approved by the Principal Investigator.
• Insufficient medical insurance according to local regulations.
• Pregnant woman or a pregnancy detected with a positive serum pregnancy test performed at the screening visit or lactating women

Sponsors & Collaborators

• Bioprojet: lead

MeSH Terms

Conditions

Alcohol-Induced Disorders, Nervous System

Interventions

pitolisant

Condition Hierarchy (Ancestors)

Neurotoxicity Syndromes; Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2016
• First Posted: June 15, 2016
• Study Start: October 1, 2016
• Primary Completion: December 1, 2019
• Last Updated: January 12, 2017

Record last verified: 2016-06