BACLOFEN FOR IMPROVING BENZODIAZEPINE TITRATION IN BENZODIAZEPINE DEPENDENCE. BABET

The primary objective of this study is to evaluate the **efficacy** of baclofen, compared to placebo, in reducing benzodiazepine doses in patients with benzodiazepine use disorder. This is clinically relevant as benzodiazepine use disorder is a significant concern in psychiatry and addiction medicine, and effective interventions are needed to manage and reduce dependency on these medications.

Secondary objectives include: - Assessing the safety of baclofen in reducing benzodiazepine doses in patients with benzodiazepine use disorder. - Evaluating the efficacy of baclofen in increasing the frequency of discontinuation of benzodiazepine use after 4 months. - Assessing the efficacy of baclofen on quality of sleep, symptoms of anxiety, symptoms of depression, quality of life, craving, and withdrawal symptoms.

The clinical trial involves participants diagnosed with **benzodiazepine use disorder** (BUD), as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 criteria. The study population includes both male and female subjects, aged between 18 and 65 years. Participants are required to have an average daily benzodiazepine dosage between 50 mg and 200 mg of diazepam equivalents over the 28 days prior to inclusion and must have been using benzodiazepines for more than 12 weeks. The trial does not involve a vulnerable population. Participants must have experienced at least one history of BUD treatment failure, defined as a failure to withdraw from the full dose according to a previously established tapering schedule. Women of childbearing potential are required to have a negative pregnancy test at inclusion and must use effective contraception throughout the trial. All participants must be affiliated with a social security system and capable of providing free, informed, and written consent. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the efficacy of **baclofen** in reducing benzodiazepine doses in patients with benzodiazepine use disorder. This study is a randomized, double-blind, placebo-controlled trial, with an estimated duration extending until December 2026. Participants will be randomly assigned to receive either baclofen or a placebo, with the primary objective being the difference in total benzodiazepine consumption, measured in mg-diazepam, between the 28 days before inclusion and the last 28 days before the final visit on Day 62/64 of randomization.

The trial will commence with a screening visit to confirm eligibility based on criteria such as age, benzodiazepine use disorder severity, and previous treatment failures. Participants will be required to have an average daily benzodiazepine dosage between 50 mg and 200 mg-diazepam over the 28 days prior to inclusion. The study will include several follow-up visits to monitor the efficacy and safety of the treatment, with assessments including benzodiazepine withdrawal severity, craving scores, anxiety, depression, sleep quality, and quality of life. The end-of-study visit will evaluate the primary and secondary endpoints, including the frequency of adverse events and benzodiazepine discontinuation.

Participant involvement is expected to last up to 18 weeks, with conditions for early termination including serious adverse events or withdrawal of consent. The trial will adhere to rigorous ethical standards, ensuring informed consent and the protection of participant welfare throughout the study period.

The clinical trial involves the administration of **Baclofen**, a chemical substance used as a muscle relaxant, to facilitate benzodiazepine tapering in cases of severe addiction. Baclofen is administered orally in a pharmaceutical form identified as PHF00231MIG. The maximum daily dose is 60 mg, with a total maximum dose of 5460 mg over a treatment period of up to 13 weeks. The trial aims to assess the efficacy of Baclofen in reducing benzodiazepine doses in patients with benzodiazepine use disorder.

**Zopiclone** is included as an auxiliary treatment in the trial. It is administered orally in the pharmaceutical form PHF00082MIG. The maximum daily dose is 200 mg, with a total maximum dose of 25200 mg over a treatment period of up to 18 weeks. Zopiclone is a chemical substance classified under the ATC code N05CF01.

**Zolpidem**, another auxiliary treatment, is administered orally in the pharmaceutical form PHF00149MIG. The active substances in this formulation are **Azelastine Hydrochloride** and **Fluticasone Propionate**, both of which are chemical substances. The maximum daily dose is 200 mg, with a total maximum dose of 25200 mg over a treatment period of up to 18 weeks. Zolpidem is classified under the ATC code N05CF02.

The trial also includes the use of **Benzodiazepine Derivatives** as auxiliary treatments. These are administered orally in pharmaceutical forms PHF00245MIG and PHF00006MIG. The maximum daily dose for these derivatives is 200 mg, with a total maximum dose of 25200 mg over a treatment period of up to 18 weeks. They are classified under the ATC code N05CD and N05BA, respectively.

**Cellulose Microcrystalline** is used as a placebo in the trial. It does not have a specified pharmaceutical form or active substance name, and it is not classified under any ATC code. The role of this substance in the trial is to serve as a comparator to assess the efficacy of Baclofen.

The efficacy of **baclofen** in reducing benzodiazepine doses in patients with benzodiazepine use disorder will be assessed through a clinical trial. The primary endpoint for evaluating efficacy is the difference in total benzodiazepine consumption, measured in mg-diazepam, between the 28 days prior to inclusion in the clinical trial and the last 28 days before visit 5 on Day 62/64 of randomization. Secondary endpoints include the frequency of serious and non-serious adverse events of special interest, frequency of all-cause study discontinuations, and frequency of benzodiazepine discontinuation at the last visit of the treatment period, assessed through self-report and urine tests.

Additional secondary endpoints involve the assessment of benzodiazepine withdrawal severity using the Clinical Institute Withdrawal Assessment of Benzodiazepine (CIWA-B), craving scores via the Visual Analog Scale (VAS), anxiety symptoms using the State Trait Inventory Anxiety (STAI-Y), depression scores with the Montgomery-Åsberg Depression Rating Scale (MADRS), subjective sleep quality through the Pittsburgh Sleep Quality Index (PSQI), and quality of life using the SF-12 v2. These parameters will be measured and collected at specified timepoints throughout the trial to ensure comprehensive analysis of the efficacy of baclofen in the target population.