Clinical trial NCT05814016: A Study of Danavorexton in People With Obstructive Sleep Apnea After General Anesthesia for Abdominal Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sleep Apnea
Keywords: Drug Therapy
Obstructive Sleep Apnea
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2023-04-14
Enrollment: 41
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: Key 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).

Primary outcomes:
measure: Number of Participants who Maintain Respiratory Stability for 120 Minutes in the Postanesthesia Care Unit (PACU)
timeFrame: Day 1
Secondary outcomes:
measure: Number of Episodes of Respiratory Instability per Participant Within 120 Minutes in the PACU
timeFrame: Day 1
measure: Plasma Concentration of Danavorexton at the End of Infusion (Ceoi)
timeFrame: Pre-dose within 1 hour before surgery and 24 hours post start of the infusion up to Day 2
measure: Number of Participants with At Least One Occurrence of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to 12 months
measure: Number of Participants with At Least One Occurrence of ≥1 Markedly Abnormal Value (MAV) in Post-Study Drug Laboratory Values
timeFrame: Up to 12 months
measure: Number of Participants with At Least One Occurrence of ≥1 MAV in Post-Study Drug Vital Signs
timeFrame: Up to 12 months
measure: Number of Participants with At Least One Occurrence of ≥1 MAV on Post-Study Drug ECGs
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Sheffield
country: United States
facility: Helen Keller Hospital
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic - PPDS - Hospital
state: Arizona
city: La Jolla
country: United States
facility: UCSD
state: California
city: West Hollywood
country: United States
facility: Cedars Sinai Medical Hospital
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville - PPDS
state: Florida
city: Miami
country: United States
facility: University of Miami - Leonard M. Miller School of Medicine
state: Florida
city: Miami
country: United States
facility: Medical Research Center - Clinic/Outpatient Facility
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Louisville
country: United States
facility: University of Louisville - Hospital
state: Kentucky
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Mullica Hill
country: United States
facility: Inspira Health
state: New Jersey
city: Mineola
country: United States
facility: NYU Langone
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Cleveland
country: United States
facility: Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin, Inc.
state: Wisconsin
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: