Evaluating Sivopixant, Acetazolamide, and SASS-001 for Sleep Apnea

Inclusion 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

Exclusion Criteria:

* 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