A Study of Danavorexton in People With Obstructive Sleep Apnea After General Anesthesia for Abdominal Surgery

Study Overview
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Brief Summary
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The main aim is to see if danavorexton can help improve people's breathing in the recovery room after abdominal surgery.

Detailed Description
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The drug being tested in this study is called danavorexton. Danavorexton is being tested in people who have moderate to severe obstructive sleep apnea undergoing general anesthesia for abdominal surgery. The study will enroll approximately 180 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three groups-which will remain undisclosed/unknown to the participant and study doctor during the study (unless there is an urgent medical need): Danavorexton high dose Danavorexton low dose Placebo All participants will receive an intravenous (IV) infusion on Day 1 of the treatment period. This multi-center study will be conducted in approximately 20 sites in the United States. The overall time for participants to participate in the study will be up to approximately 12 months.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of a Single Intravenous Infusion of Danavorexton in Participants With Moderate to Severe Obstructive Sleep Apnea Undergoing General Anesthesia for Abdominal Surgery

Conditions
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Sleep Apnea

Intervention / Treatment
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* Drug: Danavorexton
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant has a body mass index (BMI) within the range of 18.5 to 50 kg/m^2, inclusive. The participant has an apnea-hypopnea index (AHI) or respiratory event index (REI) of 15 to 40 (inclusive) based on an in-clinic polysomnography (PSG) test or an at-home sleep test within the last 5 years. Those with suspected obstructive sleep apnea (OSA) but without a PSG-based or home sleep test-based OSA diagnosis will be included based on a STOP-Bang questionnaire ≥5 and the at-home sleep test. The participant is scheduled for abdominal surgery that will include at least 1 inpatient overnight stay. The participant is scheduled to undergo a surgery requiring general anesthesia and endotracheal intubation. The participant's surgery, as planned, is anticipated to require use of IV opioids in the postanesthesia care unit (PACU). The duration of the participant's surgery (ie, procedural time) is expected to be approximately 1.5 to 4 hours. The participant has an American Society of Anesthesiologists (ASA) Classification of II to III. Exclusion Criteria: The participant is undergoing liver or kidney surgery. The participant has a planned transfer to the intensive care unit (ICU) from the operating room. For the participant, immediate continuous positive airway pressure/bilevel positive airway pressure (CPAP/BiPAP) use in the PACU is anticipated or planned. The participant has undergone major surgery or donated or lost ≥1 unit of blood (approximately 500 mL) within 4 weeks before the screening visit. The participant has received chemotherapy or radiation therapy within 4 weeks before administration of the study drug. The participant has poorly controlled diabetes with an episode of ketoacidosis within 6 months of the screening visit. The participant has a positive test result for hepatitis B surface antigen, hepatitis C virus (HCV), human immunodeficiency virus (HIV) antibody/antigen at screening. The participant has uncontrolled hypertension or unstable cardiovascular disease (presence of acute coronary syndrome, unstable angina, myocardial infarction <3 months, severe valvular disease, or severe structural heart disease), severe heart failure, or any condition requiring a pacemaker or defibrillator. The participant has a screening electrocardiogram (ECG) with a QT interval with Fridericia correction method (QTcF) >450 milliseconds [ms] (for men) or >470 ms (for women).

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Dose Danavorexton<br>Participants will receive danavorexton intravenous (IV) infusion as high dose on Day 1 of the treatment period. | Drug: Danavorexton<br>* Danavorexton IV infusion.<br>* Other names: TAK-925;|
| Experimental: Low Dose Danavorexton<br>Participants will receive danavorexton IV infusion as low dose on Day 1 of the treatment period. | Drug: Danavorexton<br>* Danavorexton IV infusion.<br>* Other names: TAK-925;|
| Placebo Comparator: Placebo<br>Participants will receive a placebo-matching danavorexton IV infusion on Day 1 of the treatment period. | Drug: Placebo<br>* Placebo matching danavorexton IV infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Maintain Respiratory Stability for 120 Minutes in the Postanesthesia Care Unit (PACU) | Respiratory stability in the PACU will be considered as having been achieved if the participant can breathe without problems for 120 minutes in the PACU. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Episodes of Respiratory Instability per Participant Within 120 Minutes in the PACU | The number of episodes of respiratory instability during 120 minutes in the PACU will be assessed. | Day 1 | 
| Plasma Concentration of Danavorexton at the End of Infusion (Ceoi) |  | Pre-dose within 1 hour before surgery and 24 hours post start of the infusion up to Day 2 | 
| Number of Participants with At Least One Occurrence of Treatment-Emergent Adverse Events (TEAEs) | TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a study intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the study intervention or medicinal product. | Up to 12 months | 
| Number of Participants with At Least One Occurrence of ≥1 Markedly Abnormal Value (MAV) in Post-Study Drug Laboratory Values |  | Up to 12 months | 
| Number of Participants with At Least One Occurrence of ≥1 MAV in Post-Study Drug Vital Signs |  | Up to 12 months | 
| Number of Participants with At Least One Occurrence of ≥1 MAV on Post-Study Drug ECGs |  | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy, Obstructive Sleep Apnea