Evaluation of Baclofen as an Adjunctive Therapy for Reducing Pharmaceutical GHB Requirements in Inpatient Detoxification for GHB Use Disorder

The primary objective of this study is to evaluate whether **baclofen** as an add-on therapy can reduce the requirement for pharmaceutical gamma-hydroxybutyrate (GHB) during inpatient detoxification in patients diagnosed with GHB use disorder (GUD). This is clinically relevant as it may offer a more effective detoxification strategy, potentially improving patient outcomes and reducing the dependency on GHB during treatment.

The clinical trial focuses on individuals diagnosed with **GHB use disorder** (GUD) as per DSM-V-TR criteria, specifically targeting those requiring intramural GHB detoxification and consuming more than 50ml of GHB per day. The study population includes both male and female participants over the age of 18, without any specific vulnerability considerations. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the need for inpatient detoxification, and participants are expected to have a significant history of GHB use. Lifestyle factors such as diet and physical activity are not specified, and the trial does not target a vulnerable population. The primary objective is to evaluate the efficacy of baclofen as an add-on therapy in reducing the need for pharmaceutical GHB during detoxification.

The clinical trial is designed to evaluate the efficacy of **baclofen** as an add-on therapy in reducing the need for pharmaceutical **gamma-hydroxybutyrate (GHB)** during inpatient detoxification for patients diagnosed with GHB use disorder (GUD). This study is a randomized, double-blind, controlled trial, categorized as a Phase IV proof-of-concept study. The trial is expected to commence recruitment on March 1, 2024, and conclude by July 31, 2026. Participants will be randomly assigned to receive either Baclofen Mylan 10 mg or 25 mg tablets, or a placebo, administered orally. The trial will also utilize Xyrem 500 mg/mL oral solution as an auxiliary treatment.

The study will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the **screening visit**, eligibility will be assessed based on criteria such as a diagnosis of GUD according to DSM-V-TR criteria, a daily GHB use of more than 50 mL, and age over 18 years. Follow-up visits will be scheduled to monitor the dosage of pharmaceutical GHB and assess the primary endpoint, which is the pharmaceutical GHB dosage at the end of the titration phase. The end-of-study visit will evaluate the overall outcomes and any adverse events.

Participant involvement is expected to last for a maximum treatment period of 12 weeks. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse events that pose a risk to the participant's health. The trial aims to provide valuable insights into the potential benefits of baclofen in managing GHB use disorder, contributing to improved detoxification strategies.

The clinical trial involves the use of **Baclofen**, a chemical substance, as an experimental medication. Two formulations of Baclofen are utilized: **Baclofen Mylan 10 mg tablets** and **Baclofen Mylan 25 mg tablets**. Both formulations are administered orally. The maximum daily dose for Baclofen is 120 mg, with a maximum total dose of 30 mg per administration. The treatment period for Baclofen is limited to 1 day. Baclofen is classified under the ATC code M03BX01 and is manufactured by MYLAN B.V. The tablets are not formulated for pediatric use and are not designated as orphan drugs.

In addition to Baclofen, the trial includes the use of **Xyrem 500 mg/mL oral solution**, which contains the active substance **Sodium Oxybate**. This auxiliary medication is also administered orally. The maximum daily dose for Xyrem is 200 mL, with a treatment period extending up to 12 months. Sodium Oxybate is a chemical substance and is not formulated for pediatric use. The product is manufactured by UCB PHARMA S.A. (ANDERL BE) and is not designated as an orphan drug. The use of Xyrem in the trial serves as a comparator treatment to assess the efficacy of Baclofen in reducing the need for pharmaceutical GHB during inpatient detoxification in patients with GHB use disorder (GUD).

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the dosage of pharmaceutical **gamma-hydroxybutyrate (GHB)** required at the end of the titration phase during inpatient detoxification in patients with **gamma-hydroxybutyrate use disorder (GUD)**. The trial aims to determine if the addition of baclofen therapy can reduce the need for pharmaceutical GHB in these patients. The assessment will focus on the change in GHB dosage, providing a quantitative measure of the treatment's impact on the detoxification process. The trial is designed as a proof-of-concept and dose-finding study, conducted in a Phase 4 setting, to explore the off-label use of baclofen in this context.