Study of AD981 Versus Placebo in Obesity Hypoventilation Syndrome

NCT05448443 | Completed Phase 2

• 1 other identifier: 09J201
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double blind, placebo-controlled, cross-over, phase II, single center efficacy study of AD981 in patients with obesity hypoventilation syndrome documented by polysomnography (PSG) and transcutaneous, overnight measurement of CO2 (PtcCO2).

Conditions

Obesity Hypoventilation Syndrome (OHS)

Outcome Measures

Primary Outcomes (1)

• Nocturnal transcutaneous CO2 pressure (PtcCO2)

  From baseline to the last day of treatment (14 days after the start of each treatment period)

Secondary Outcomes (2)

• Proportion of participants without nocturnal hypoventilation

  From baseline to the last day of treatment (14 days after the start of each treatment period)

• Apnea-Hypopnea Index (AHI)

  From baseline to the last day of treatment (14 days after the start of each treatment period)

Study Arms (2)

AD981

EXPERIMENTAL

AD981

Drug: AD981

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

AD981 DRUG

Oral administration of AD981 in the morning and before sleep for 14 days

AD981

Placebo OTHER

Oral administration of placebo in the morning and before sleep for 14 days

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to understand the nature of the study and sign the informed consent
• BMI \> 35 kg/m2 and presence of nocturnal hypoventilation
• Previous surgical treatment for OSA is allowed if ≥ 1 year prior to enrollment
• If in treatment, CPAP or BPAP or mandibular advancement device or positional therapy intolerance or poor compliance

You may not qualify if:

• Narcolepsy, craniofacial malformation, renal failure, hepatic disease, schizophrenia, schizoaffective disorder or bipolar disorder, cognitive dysfunction, severe neurological disorder, pheochromocytoma, adrenocortical insufficiency, hyperchloremic acidosis.
• Respiratory (COPD, ILD, oxygen therapy) or cardiac (Heart Failure, Atrial fibrillation, established severe peripheral arterial disease) disease or hypertension requiring more than 3 medications for control
• Cardiomyopathies, heart malformation or structural heart alterations, severe rhythm disorders, established coronary heart disease or other cardiac conditions, which could determine sudden death
• Attempted suicide or suicidal ideation
• Drugs of abuse or substance use disorder
• A significant illness or infection requiring medical treatment in the past 30 days.
• Untreated narrow angle glaucoma.
• Women who are pregnant or nursing.
• Treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors, or monoamine oxidase inhibitors (MAOI) or linezolid within 14 days of the start of treatment, allergies to sulfonamides.
• Diabetes with unstable glucose control in the past 15 days.
• \> 500 mg/day of Aspirin
• Low sodium or potassium.
• Any condition that in the investigator's opinion would present an unreasonable risk to the participant.
• History of using oral or nasal devices (such as mandibular advancement devices) for the treatment of OSA may enroll as long as the devices are not used during participation in the study for at least 2 weeks prior to study begin.
• History of using devices to affect participant sleeping position for the treatment of OSA, e.g. to discourage supine sleeping position, may enroll as long as the devices are not used during participation in the study.

Sponsors & Collaborators

• Istituto Auxologico Italiano: lead
• Apnimed Inc.: collaborator
• VIS Ethic Research Srl: collaborator
• University of Florence: collaborator
• STM Pharma PRO srl: collaborator

Study Sites (1)

Istituto Auxologico Italiano,Ospedale San Luca

Milan, Italy

Location

Related Publications (1)

• Perger E, Parati G, Faini A, Gell L, Faverio P, Luppi F, Bertoli S, Brunani A, Bigagli E, Lombardi C, Taranto-Montemurro L. Acetazolamide Plus Atomoxetine for Obesity Hypoventilation Syndrome Treatment. Chest. 2025 Sep 25:S0012-3692(25)05384-X. doi: 10.1016/j.chest.2025.09.019. Online ahead of print.

  PMID: 41015199 DERIVED

MeSH Terms

Conditions

Obesity Hypoventilation Syndrome

Condition Hierarchy (Ancestors)

Sleep Apnea, Obstructive; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Hypoventilation; Respiratory Insufficiency; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Officials

• Elisa Perger, MD

  Istituto Auxologico Italiano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients who meet the eligibility criteria will be randomized equally to receive AD981 or matching placebo. After 14 days of treatment and a washout period, the patients crossover to the other treatment arm for 14 days.

Study Record Dates

• First Submitted: July 1, 2022
• First Posted: July 7, 2022
• Study Start: June 21, 2022
• Primary Completion: May 8, 2024
• Study Completion: May 8, 2024
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)