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).

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