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

NCT06776432 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: SVA-SAS-201
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Sleep Apnea

Keywords

sleep apnea; obstructive sleep apnea; central sleep apnea

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint - Change in apnea-hypopnea index (SASS-001 arm vs baseline at Visit 7 polysomnography). Scale is minimum -60 to max 60. Lower scores mean improvement from baseline.

  up to 6 weeks

Secondary Outcomes (1)

• Secondary Endpoint - Change in apnea-hypopnea index (Sivopixant alone vs baseline at Visit 5 polysomnography). Scale is minimum -60 to max 60. Lower scores mean improvement from baseline.

  up to 6 weeks

Other Outcomes (1)

• Additional Secondary Endpoint: Change in apnea-hypopnea index (SASS-001 vs Acetazolamide alone - visit 7 vs visit 6 polysomnography). Scale is minimum -60 to max 60. Lower scores mean improvement from baseline.

  Two weeks

Study Arms (4)

Part A: Sivopixant

ACTIVE COMPARATOR

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

Drug: Sivopixant

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Part B I: Acetazolamide

ACTIVE COMPARATOR

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

Drug: Acetazolamide

Part B II: SASS-001

ACTIVE COMPARATOR

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

Drug: SASS-001

Interventions

Sivopixant DRUG

Administered as specified in the treatment arm

Part A: Sivopixant

Placebo DRUG

Administered as specified in the treatment arm.

Placebo

Acetazolamide DRUG

Administered as specified in the treatment arm

Part B I: Acetazolamide

SASS-001 DRUG

Administered as specified in the treatment arm

Part B II: SASS-001

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To enroll, subjects need to have a previous diagnosis of at least one or more of the following comorbidities:
• Stable heart failure with reduced ejection fraction (NYHA class 1-3 inclusive) with or without atrial fibrillation
• Heart failure with preserved ejection fraction (NYHA class 1-3 inclusive) and hypertension (BP\>120/80 mmHg at screening visit despite the treatment with ≥2 antihypertensives) with or without atrial fibrillation
• Persistent atrial fibrillation (continuous and sustained for more than 7 days, rate controlled with resting HR\<100bpm)1 without heart failure
• History of primary (essential) hypertension with BP at screening visit \>130/80 mmHg despite the treatment with \>2 antihypertensives
• Evidence of complex sleep apnea (CPAP-emergent central sleep apnea with documented CAI\>5 events/h on CPAP within 1 year from screening)
• Standard care for heart failure and atrial fibrillation for at least 3 weeks before the screening visit
• OSA measures Average ODI4 between 7 and 55 events/h, inclusive, and average SpO2 ≥88% from continuous home pulse oximetry recordings at screening.
• AHI4 (Hypopneas defined by 4% oxygen desaturation) of \>10 to ≤60 events/h
• At minimum of 25% central or mixed apneas (as proportion of total apneas) with a minimum of 2.5 central or mixed apneas/hour of sleep
• OR evidence of clear Cheyne-Stokes breathing pattern during the baseline PSG (regardless of central apnea component).
• OR evidence of OSA with LGn \>0.5 at the baseline PSG (regardless of central apnea component) Average SpO2 during sleep ≥88%
• Weight BMI between 18.5 and 40 kg/m2 for men, or 42 kg/m2 for women, inclusive
• Male participants If male and sexually active with female partner(s) of childbearing potential, participant must agree, from Study Day 1 through 1 week after the last dose of study drug, to practice the protocol specified contraception. Male participants must refrain from donating sperm for the duration of the study and for 3 months after the last dose of study treatment.
• Female participants If a woman of childbearing potential (WOCBP), the participant must agree, from Study Day 1 through 1 week after the last dose of study drug, to practice the protocol specified contraception. All WOCBP must have negative result of a serum pregnancy test performed at screening.

You may not qualify if:

• 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.
• Medical Conditions 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 severe 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 screening. 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.

Sponsors & Collaborators

• Shionogi: lead

Study Sites (9)

Altman Clinical and Translational Research Institute (ACTRI)

La Jolla, California, 92037, United States

Location

Teradan Clinical Trials

Brandon, Florida, 33511, United States

Location

PharmaDev Clinical Research Institute, LLC

Miami, Florida, 33176, United States

Location

Infinity Medical Research

North Dartmouth, Massachusetts, 02747, United States

Location

John D. Dingell VA Medical Center

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Intrepid Research, LLC

Cincinnati, Ohio, 45245, United States

Location

OnSite Clinical Solutions

Rock Hill, South Carolina, 29732, United States

Location

Huntsville Research Institute LLC

Huntsville, Texas, 77340, United States

Location

MeSH Terms

Conditions

Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Sleep Apnea, Central

Interventions

sivopixant; Acetazolamide

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Chief Scientific Officer

  Apnimed

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2025
• First Posted: January 15, 2025
• Study Start: April 2, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (9)