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

Phase 2
Terminated
Conditions
Sleep Apnea
Interventions
Drug: Placebo
Registration Number
NCT05814016
Lead Sponsor
Takeda
Brief Summary

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

Detailed Description

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
41
Inclusion Criteria
  1. The participant has a body mass index (BMI) within the range of 18.5 to 50 kg/m^2, inclusive.

  2. The participant has diagnosed or suspected moderate or severe obstructive sleep apnea (OSA) based on one of the criteria below:

    a. The participant has a snoring, tiredness, observed apnea, high blood pressure, body mass index, age, neck circumference, and gender questionnaire (STOP-Bang) score ≥5 at the screening visit. OR b. The participant has a diagnosis of moderate or severe OSA based on an in-clinic polysomnography (PSG) or home sleep test with an apnea-hypopnea index (AHI) or respiratory event index (REI) score of ≥15 and they have not had significant weight loss since their diagnostic test, in the judgment of the investigator.

  3. The participant is scheduled for major abdominal surgery invading the intraperitoneal or retroperitoneal space (open or laparoscopic) that will require at least 1 inpatient overnight stay.

  4. The participant is scheduled to undergo a surgery requiring general anesthesia and endotracheal intubation.

  5. The participant's surgery, as planned, is anticipated to require use of IV opioids in the postanesthesia care unit (PACU).

  6. The duration of the participant's surgery (i.e., incision to last stitch) is expected to be at least 2 hours and up to approximately 8 hours.

  7. The participant has an American Society of Anesthesiologists (ASA) Classification of II to III.

Key

Exclusion Criteria
  1. The participant has an AHI or REI score <15 based on in-clinic PSG test or at-home sleep test within 2 years before screening.
  2. The participant is undergoing liver or kidney surgery.
  3. The participant has a planned transfer to the intensive care unit (ICU) from the operating room.
  4. For the participant, immediate (continuous positive airway pressure [CPAP]/ bilevel positive airway pressure [BiPAP]) use in the PACU is anticipated or planned.
  5. The participant has undergone major surgery or donated or lost ≥1 unit of blood (approximately 500 mL) within 4 weeks before the screening visit.
  6. The participant has received chemotherapy or radiation therapy within 4 weeks before administration of the study drug.
  7. The participant has poorly controlled diabetes with an episode of ketoacidosis within 6 months of the screening visit.
  8. The participant has a positive test result for hepatitis B surface antigen, hepatitis C virus (HCV), human immunodeficiency virus antibody/antigen at screening.
  9. 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.
  10. 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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants will receive a placebo-matching danavorexton IV infusion on Day 1 of the treatment period.
Low Dose DanavorextonDanavorextonParticipants will receive danavorexton IV infusion as low dose on Day 1 of the treatment period.
High Dose DanavorextonDanavorextonParticipants will receive danavorexton intravenous (IV) infusion as high dose on Day 1 of the treatment period.
Primary Outcome Measures
NameTimeMethod
Number of Participants who Maintain Respiratory Stability for 120 Minutes in the Postanesthesia Care Unit (PACU)Day 1

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.

Secondary Outcome Measures
NameTimeMethod
Number of Participants with At Least One Occurrence of ≥1 MAV in Post-Study Drug Vital SignsUp to 12 months
Number of Participants with At Least One Occurrence of ≥1 Markedly Abnormal Value (MAV) in Post-Study Drug Laboratory ValuesUp to 12 months
Number of Participants with At Least One Occurrence of ≥1 MAV on Post-Study Drug ECGsUp to 12 months
Number of Episodes of Respiratory Instability per Participant Within 120 Minutes in the PACUDay 1

The number of episodes of respiratory instability during 120 minutes in the PACU will be assessed.

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)Up to 12 months

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.

Trial Locations

Locations (19)

Helen Keller Hospital

🇺🇸

Sheffield, Alabama, United States

Mayo Clinic - PPDS - Hospital

🇺🇸

Phoenix, Arizona, United States

UCSD

🇺🇸

La Jolla, California, United States

Cedars Sinai Medical Hospital

🇺🇸

West Hollywood, California, United States

Mayo Clinic Jacksonville - PPDS

🇺🇸

Jacksonville, Florida, United States

University of Miami - Leonard M. Miller School of Medicine

🇺🇸

Miami, Florida, United States

Medical Research Center - Clinic/Outpatient Facility

🇺🇸

Miami, Florida, United States

University of South Florida

🇺🇸

Tampa, Florida, United States

Cleveland Clinic Florida

🇺🇸

Weston, Florida, United States

Rush University

🇺🇸

Chicago, Illinois, United States

University of Louisville - Hospital

🇺🇸

Louisville, Kentucky, United States

Brigham and Womens Hospital

🇺🇸

Boston, Massachusetts, United States

Inspira Health

🇺🇸

Mullica Hill, New Jersey, United States

NYU Langone

🇺🇸

Mineola, New York, United States

Stony Brook University Medical Center

🇺🇸

Stony Brook, New York, United States

Fairview Hospital

🇺🇸

Cleveland, Ohio, United States

Cleveland Clinic Hospital

🇺🇸

Cleveland, Ohio, United States

Ohio State University Wexner Medical Center

🇺🇸

Columbus, Ohio, United States

The Medical College of Wisconsin, Inc.

🇺🇸

Milwaukee, Wisconsin, United States

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