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

Inclusion Criteria:

• OSA measures

• Average oxygen desaturation index 4 (ODI4) ≥ 7 and < 55 events/h and averageSpO2≥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 expresswillingness to discontinue treatment for a minimum of 7 days before the baselineSpO2 assessments

• Patients who discontinued PAP

• Naïve to PAP

Exclusion Criteria:

• Sustained SpO2<93% during wakefulness or mean SpO2<88% during sleep, calculated fromPSG 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 decompensatedheart failure

• History of stroke

• History of sustained ventricular tachyarrhythmias or other severe arrhythmiaswithout defibrillator implanted

• Heart failure primarily caused by valvular, post-partum cardiomyopathy or activemyocarditis

• History of obesity-hypoventilation syndrome or respiratory disturbance due toopioids

• History of bronchiectasis and uncontrolled asthma

• History of chronic obstructive pulmonary disease (COPD) with a forced expiratoryvolume 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 ≥3tonsillar hypertrophy, etc.), pronounced micrognathia, or pronounced incompletedevelopment of the lower jaw

• History of schizophrenia, schizoaffective disorder or bipolar disorder according toDiagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) or InternationalClassification 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 toScreening Visit

• A significant illness or infection requiring medical treatment in the past 30 daysas 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, oralor nasal devices, or positional devices, may enroll as long as the devices have notbeen used for at least 1 week prior to first PSG and are not used duringparticipation 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 arenaïve to PAP and patients who discontinued PAP previously. PAP compliant patientscannot 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