This Phase 3 clinical trial is designed to evaluate the efficacy and safety of maridebart cafraglutide compared to placebo over a 52-week period in adults with obstructive sleep apnea (OSA) who are receiving positive airway pressure (PAP) therapy and are living with overweight or obesity.

Inclusion Criteria:

• AHI ≥ 15 on polysomnography at day 1 before randomization.
• BMI ≥ 27 kg/m^2 at screening.
• History of at least 1 unsuccessful attempt at weight loss by diet and exercise.
• On positive airway pressure (PAP) therapy for at least 3 consecutive months before screening and plan to continue PAP therapy during the trial.

Exclusion Criteria:

• Had any previous or planned upper airway surgery for sleep apnea or major ear, nose, or throat surgery.
• Significant craniofacial abnormalities that may affect breathing at screening.
• Diagnosis of Central Apnea with % of central apneas/hypopneas ≥ 50%, and/or diagnosis of Cheyne Stokes Respiration.
• Active device treatment of obstructive sleep apnea other than PAP therapy (eg, oral appliances), or other treatments, that in the opinion of the investigator, may interfere with trial outcomes, unless willing to stop treatment at screening and throughout the trial.
• Respiratory diseases such as obesity hypoventilation syndrome or daytime hypercapnia, or neuromuscular diseases such as myasthenia gravis or other conditions that could interfere with the results of the trial in the opinion of the investigator.
• Have personal circumstances or job-related responsibilities that prevent a 7-day PAP withdrawal before polysomnography testing during the course of the trial.

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.