A Phase 2A Double-Blind Randomized, Controlled, Dose Escalation, Parallel- Arm, Safety and Efficacy Study of Sivopixant, Acetazolamide and SASS-001 in Sleep Apnea
Overview
- Phase
- Phase 2
- Intervention
- Sivopixant
- Conditions
- Not specified
- Sponsor
- Shionogi Apnimed Sleep Science
- Enrollment
- 60
- Locations
- 9
- Primary Endpoint
- 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.
- Status
- Recruiting
- Last Updated
- 6 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- Not provided
Arms & Interventions
Part A: Sivopixant
Participants will receive sivopixant oral tablets once daily at bedtime for 17 days.
Intervention: Sivopixant
Placebo
Participants will receive placebo to match the study drug during the 17 days of Part A followed by 13 days of Part B.
Intervention: Placebo
Part B I: Acetazolamide
After completing Part A, participants will receive acetazolamide oral tablets once daily at bedtime for 3 days.
Intervention: Acetazolamide
Part B II: SASS-001
After completing Part B I, participants will receive SASS-001 oral tablets once daily at bedtime for 10 days.
Intervention: SASS-001
Outcomes
Primary Outcomes
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.
Time Frame: up to 6 weeks
Secondary Outcomes
- 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)