Study of AD981 Versus Placebo in Obesity Hypoventilation Syndrome

Obesity Hypoventilation Syndrome (OHS) Clinical Trial

— ATOHS  

Official title:

Crossover, Double-blind, Phase 2 Study of AD981 Versus Placebo in Obesity Hypoventilation Syndrome

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05448443
• Other study ID #: 09J201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 21, 2022
• Est. completion date: April 30, 2025

Study information

• Verified date: June 2024
• Source: Istituto Auxologico Italiano
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: April 30, 2025
• Est. primary completion date: May 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

• Use of another investigational agent within 30 days or 5 half-lives, whichever is longer, prior to dosing.

• Patient currently receiving: MAOIs, Serotonin and Norepinephrine Reuptake Inhibitors, Norepinephrine Reuptake Inhibitors, Lithium, Tricyclic antidepressants, strong CYP2D6 inhibitors, other strong inhibitors cytochrome P450, thiazides diuretics, benzodiazepines, opioids, drugs with clinically significant cardiac QT-interval prolonging effects, drugs known to lower seizure threshold, amphetamines, antiepileptics, modafinil or armodafinil, beta2 agonists, antipsychotics, pseudoephedrine, phenylephrine, oxymetazoline, drugs for Parkinson's, Alzheimer's, Huntington's, Amyotrophic Lateral Sclerosis, or drugs for other neurodegenerative diseases, more than 500 mg/day of Aspirin or salicylates, sodium Phosphate.

• Known hypersensitivity to study drugs

Related Conditions & MeSH terms

• Hypoventilation
• Obesity
• Obesity Hypoventilation Syndrome
• Obesity Hypoventilation Syndrome (OHS)
• Syndrome

Intervention

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

Other:
• Placebo
Oral administration of placebo in the morning and before sleep for 14 days

Locations

Country	Name	City	State
Italy	Istituto Auxologico Italiano,Ospedale San Luca	Milano

Sponsors (5)

Lead Sponsor	Collaborator
Istituto Auxologico Italiano	Apnimed Inc., STM Pharma PRO srl, University of Florence, VIS Ethic Research Srl

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nocturnal transcutaneous CO2 pressure (PtcCO2)		From baseline to the last day of treatment (14 days after the start of each treatment period)
Secondary	Proportion of participants without nocturnal hypoventilation		From baseline to the last day of treatment (14 days after the start of each treatment period)
Secondary	Apnea-Hypopnea Index (AHI)		From baseline to the last day of treatment (14 days after the start of each treatment period)