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

Shionogi Apnimed Sleep Science

Status and phase: Invitation-only; Phase 2

Conditions: Sleep Apnea

Treatments: Drug: SASS-001; Drug: Placebo; Drug: Acetazolamide; Drug: Sivopixant

Study type: Interventional

Funder types: Industry

Identifiers

NCT06776432

SVA-SAS-201

Details and patient eligibility

About

The primary purpose of this study is to evaluate the effectiveness of sivopixant, acetazolamide and SASS-001 in adults with sleep apnea with a central component.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 4 patient groups, including a placebo group

Part A: Sivopixant

Active Comparator group

Description:

Participants will receive sivopixant oral tablets once daily at bedtime for 17 days.

Treatment:

Drug: Sivopixant

Placebo

Placebo Comparator group

Description:

Participants will receive placebo to match the study drug during the 17 days of Part A followed by 13 days of Part B.

Treatment:

Drug: Placebo

Part B I: Acetazolamide

Active Comparator group

Description:

After completing Part A, participants will receive acetazolamide oral tablets once daily at bedtime for 3 days.

Treatment:

Drug: Acetazolamide

Part B II: SASS-001

Active Comparator group

Description:

After completing Part B I, participants will receive SASS-001 oral tablets once daily at bedtime for 10 days.

Treatment:

Drug: SASS-001