Evaluation of Bupropion Hydrochloride and Naltrexone Hydrochloride in Patients with Post-Bariatric Surgery Weight Regain

The primary objective of this study is to evaluate the **dose response** of Mysimba in patients who have undergone Roux-en-Y gastric bypass or gastric sleeve surgery. This is clinically relevant as it aims to determine the optimal dosage of Mysimba for managing weight regain in patients post-bariatric surgery, potentially improving therapeutic outcomes and patient management in obesity treatment.

Secondary objectives include:

• Describing the persistence of therapy with Mysimba after bariatric surgery.
• Describing the maximal tolerated dosage of Mysimba.
• Studying adverse effects associated with the use of Mysimba.
• Monitoring and comparing long-term weight loss (up to 12 months) after the initiation of Mysimba in both study groups.
• Evaluating eating behavior in patients with weight regain after bariatric surgery who used Mysimba compared to those on the regular module, using the YFAS 2.0 questionnaire.

The clinical trial involves a study population comprising both **male** and **female** participants aged between 18 and 74 years. The participants are individuals who have undergone either a Roux-en-Y gastric bypass or sleeve gastrectomy, with a pre-surgery **BMI** of at least 35.0 kg/m². The trial focuses on those who have experienced a weight gain of more than 5% after reaching the plateau phase of their lowest weight post-surgery. Additionally, a control cohort includes patients who are obese, with a BMI greater than 30 kg/m², and are on a successful Mysimba steady maintenance dose. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific inclusion criteria related to their surgical history and weight management post-surgery. Lifestyle factors such as diet and physical activity are not explicitly detailed in the available data.

The clinical trial is designed to evaluate the **dose response** of Mysimba, a combination of **bupropion hydrochloride** and **naltrexone hydrochloride**, in patients experiencing weight regain following bariatric surgery, specifically Roux-en-Y gastric bypass or sleeve gastrectomy. This study is a randomized, double-blind, controlled trial, aiming to assess the efficacy of the medication in achieving significant weight loss, defined as more than 5% reduction in body weight, over a period of 22 weeks. The trial is expected to conclude by April 2026, with recruitment having commenced in April 2023.

Participants will undergo a series of study visits, beginning with an inclusion visit to screen for eligibility based on criteria such as age (18-74 years), pre-surgery BMI (≥35 kg/m²), and post-surgery weight gain (>5% after reaching the lowest weight plateau). Follow-up visits will be scheduled to monitor progress, adherence to the treatment regimen, and any adverse effects. The end-of-study visit will evaluate the primary endpoint, which is the effect of the combination therapy on weight loss compared to a control group receiving the standard behavioral obesity treatment (BOT) module alone.

The expected duration of participant involvement is approximately 50 weeks, accounting for the treatment period and follow-up assessments. 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 is conducted under strict regulatory standards to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Mysimba** 8 mg/90 mg **prolonged-release tablets**. This experimental medication contains two active substances: **bupropion hydrochloride** and **naltrexone hydrochloride**. The pharmaceutical form of the medication is a prolonged-release tablet, designed to release the active ingredients over an extended period. The route of administration is oral, and the maximum daily dose is 272 mg. The treatment period is limited to a maximum of 50 days. The medication is manufactured by Orexigen Therapeutics Ireland Limited and is not formulated for pediatric use.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the dose response of Mysimba in patients who have experienced weight regain following Roux-en-Y gastric bypass or gastric sleeve surgery. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the effect of the combination of **naltrexone** and **bupropion** with the BOT module on achieving successful weight loss, defined as more than 5% weight loss after 22 weeks. This will be compared to the regular BOT module alone in patients experiencing weight regain after bariatric surgery. The assessment of body weight is a standard part of the treatment protocol. The trial aims to determine the dose response of Mysimba following Roux-en-Y gastric bypass or sleeve gastrectomy. The trial is set to run until April 1, 2026, with recruitment having started on April 2, 2023. The maximum treatment period for participants is 50 weeks, and the trial is categorized as a Phase II study.