Safety and Efficacy Study of Sivopixant, Acetazolamide and SASS-001 in Sleep Apnea

Eligibility Criteria

• * OSA measures
• * Average oxygen desaturation index 4 (ODI4) ≥ 7 and \< 55 events/h and average SpO2≥88% during sleep from continuous home pulse oximetry recordings at screening
• * AHI4 of \> 10 to \<60 events/h
• * Patients currently using PAP will be eligible for inclusion in the study if:
• * Non-compliant to CPAP (less than 4 hr/night for 5 days/week) and they express willingness to discontinue treatment for a minimum of 7 days before the baseline SpO2 assessments
• * Patients who discontinued PAP
• * Naïve to PAP
• * Sustained SpO2\<93% during wakefulness or mean SpO2\<88% during sleep, calculated from PSG at screening
• * Dyspnea at rest or patients with heart failure class IV NYHA
• * Blood pressure \<90/50 mmHg or \>160/100 mmHg at V1
• * Recent (\<3 months) episode of acute myocardial infarction or acute decompensated heart failure
• * History of stroke
• * History of sustained ventricular tachyarrhythmias or other severe arrhythmias without defibrillator implanted
• * Heart failure primarily caused by valvular, post-partum cardiomyopathy or active myocarditis
• * History of obesity-hypoventilation syndrome or respiratory disturbance due to opioids
• * History of bronchiectasis and uncontrolled asthma
• * History of chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted (European Respiratory Society criteria)
• * Started treatment with β-blockers \<3 months before the study. Patients not taking β-blockers or taking β-blockers for \>3 months can be enrolled.
• * Narcolepsy, restless leg syndrome requiring medication, REM sleep behavior disorder
• * Pronounced anatomical abnormalities of upper airway (adenoid vegetations, grade ≥3 tonsillar hypertrophy, etc.), pronounced micrognathia, or pronounced incomplete development of the lower jaw
• * History of schizophrenia, schizoaffective disorder or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) or International Classification of Disease tenth edition criteria
• * Medically unexplained positive screen for drugs of abuse (excluding THC/marijuana) or history of substance use disorder as defined in DSM-V within 24 months prior to Screening Visit
• * A significant illness or infection requiring medical treatment in the past 30 days as determined by investigator
• * Clinically significant cognitive dysfunction as determined by investigator.
• * Women who are pregnant or nursing
• * Participants with reduced sodium and/or potassium blood serum levels
• * Participants with suprarenal gland failure
• * Participants with hyperchloremic acidosis
• * Participants with a history of using devices for OSA treatment, including CPAP, oral or nasal devices, or positional devices, may enroll as long as the devices have not been used for at least 1 week prior to first PSG and are not used during participation in the study (through V7). Patients that are non-compliant to CPAP (less than 4hr/night for 5 days/week) can be enrolled, as well as patients who are naïve to PAP and patients who discontinued PAP previously. PAP compliant patients cannot be enrolled.
• * History of chronic oxygen therapy are excluded
• * Concomitant use of medications from the list of disallowed medications
• * Hepatic transaminases \>2X the upper limit of normal (ULN), total bilirubin \>1.5X ULN (unless confirmed Gilbert syndrome), estimated glomerular filtration rate \<40 ml/min
• * Excluded Medications
• * Digoxin, methyldigoxin, beta-methyldigoxin.
• * Opioids
• * Mecamylamine
• * Methenamine
• * Sodium Phosphates
• * Chronic use of more than 500 mg/day of Aspirin
• * GLP1 receptor agonists for weight loss, unless reached stable dose and stable weight (\<4lbs weight change per month) for 3+ months
• * Other carbonic anhydrase inhibitors (zonisamide, topiramate, etc)
• * Lithium
• * Note: Other protocol defined Inclusion/Exclusion criteria may apply