Evaluation of Baclofen as an Adjunctive Therapy in Sodium Oxybate Detoxification for Patients with Gamma-Hydroxybutyrate Use Disorder

The primary objective of this study is to evaluate the efficacy of **baclofen** as an add-on therapy in reducing the requirement for pharmaceutical gamma-hydroxybutyrate (GHB) during inpatient detoxification in patients diagnosed with GHB use disorder (GUD). This is clinically relevant as it aims to improve detoxification outcomes by potentially minimizing the dependency on GHB, thereby facilitating a safer and more effective withdrawal process. The study does not list any secondary objectives.

The clinical trial focuses on individuals diagnosed with **GHB use disorder** (GUD) as per the DSM-V-TR criteria for substance use disorder. The study population includes both male and female participants, all of whom are over the age of 18. Participants are required to have an indication for intramural GHB detoxification and a history of GHB use exceeding 50ml per day. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection of participants is based on specific inclusion criteria, ensuring that the study population is representative of individuals with significant GHB use requiring detoxification. Lifestyle factors such as diet and physical activity are not specified, but the focus remains on the medical condition and detoxification needs. The trial aims to evaluate the efficacy of baclofen as an add-on therapy to reduce the need for pharmaceutical GHB during inpatient detoxification.

The clinical trial is designed to evaluate the efficacy of **baclofen** as an add-on therapy in reducing the need for pharmaceutical **sodium oxybate** during inpatient detoxification for patients diagnosed with **GHB use disorder**. 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 August 1, 2023, and conclude by January 1, 2025. The trial will involve a series of structured visits, beginning with an inclusion visit where participants will be screened based on specific criteria, including a diagnosis of GHB use disorder according to DSM-V-TR criteria, a daily GHB use of more than 50 ml, and an age of over 18 years.

Participants will be randomly assigned to receive either Baclofen Mylan 10 mg or 25 mg tablets, or a control treatment, administered orally. The maximum daily dose of baclofen is set at 120 mg, with a treatment period of up to one month. The primary endpoint of the study is the dosage of pharmaceutical GHB required at the end of the titration phase during detoxification. Follow-up visits will be scheduled to monitor the participants' progress and adjust dosages as necessary. The end-of-study visit will assess the overall outcomes and any adverse effects experienced by the participants.

The expected duration of participant involvement is up to three months, depending on individual response and treatment adjustments. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or the occurrence of significant adverse events. 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 administration of **Baclofen**, a muscle relaxant, in two different dosages. The first experimental medication is **Baclofen Mylan 25 mg**, presented in tablet form. The active substance is **baclofen**, a chemical compound, with an ATC code of M03BX01. The tablets are administered orally, with a maximum daily dose of 120 mg and a maximum total dose of 30 mg per administration. The treatment period for this dosage is limited to one day. The medication is manufactured by MYLAN B.V. and is not a pediatric formulation.

The second experimental medication is **Baclofen Mylan 10 mg**, also in tablet form. Similar to the 25 mg formulation, the active substance is **baclofen**, and it shares the same ATC classification. The administration route is oral, with the same maximum daily dose of 120 mg and a maximum total dose of 30 mg per administration. The treatment period is also restricted to one day. This formulation is likewise produced by MYLAN B.V. and is not intended for pediatric use.

In addition to the baclofen treatments, the study includes the use of **Sodium Oxybate** as a non-experimental treatment. Sodium oxybate, also known as the sodium salt of gamma-hydroxybutyric acid, is administered orally in a liquid form with a concentration of 150 mg/ml. The maximum daily dose is 800 grams, with the same amount as the maximum total dose. The treatment period for sodium oxybate extends up to three days. This medication is used as a comparator treatment to assess the efficacy of baclofen in reducing the need for pharmaceutical GHB during inpatient detoxification in patients with gamma-hydroxybutyrate use disorder (GUD).

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the dosage of pharmaceutical **Gamma-Hydroxybutyric Acid (GHB)** at the end of the titration phase during inpatient detoxification in patients with **Gamma-Hydroxybutyric Acid Use Disorder (GUD)**. The trial aims to determine whether the addition of baclofen therapy reduces the need for pharmaceutical GHB in these patients. The assessment will focus on the reduction in GHB dosage as a measure of efficacy. The trial is designed as a proof-of-concept and dose-finding study, and it is categorized as a Phase 4 trial. The study will involve the administration of baclofen in tablet form, with a maximum daily dose of 120 mg, and will be conducted over a maximum treatment period of one week. The trial is not classified as low intervention, and it investigates the off-label use of baclofen for this specific indication.