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

Study Overview
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Brief Summary
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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.

Official Title
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A Multisite Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Pitolisant (BF2.649) For Alcohol Use Disorder Treatment

Conditions
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Alcohol Abuse, Nervous System

Intervention / Treatment
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* Drug: Pitolisant (BF2.649)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 Male subject who wants to conceive a child during the duration of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pitolisant (BF2.649)<br>Histamine H3 receptor H3R antagonist/ inverse agonist | Drug: Pitolisant (BF2.649)<br> <br> |
| Placebo Comparator: Placebo<br>placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monthly Heavy Drinking Days (HDD/month) |  | Change from Baseline of Monthly Heavy Drinking Days and at week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Time Line Follow Back (TLFB) |  | at week 24 versus Baseline | 
| Alcohol Use Disorders Identification Test (AUDIT) |  | at week 24 versus Baseline | 
| Pittsburgh Sleep Quality Index (PSQI) |  | at week 24 versus Baseline | 
| Quality of Life (SF-12) |  | at week 24 versus Baseline |