Sivopixant + Acetazolamide + SASS-001 for Sleep Apnea

Recruiting at 8 trial locations

Overseen By Chief Scientific Officer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Shionogi Apnimed Sleep Science

Must not be taking: Opioids, Digoxin, Lithium, others

Disqualifiers: Heart failure, Stroke, COPD, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of three treatments—sivopixant, acetazolamide, and SASS-001—for individuals with sleep apnea that includes central apnea, a condition where breathing stops and starts during sleep. The study aims to determine if these medications can improve sleep patterns and breathing in affected individuals. It suits those diagnosed with sleep apnea who have a history of heart issues or high blood pressure, even while on medication. Participants will try different medications at bedtime over several weeks to identify the most effective option. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in sleep apnea treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, including digoxin, opioids, and some others listed in the exclusion criteria. If you are taking any of these, you will need to stop before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that acetazolamide did not cause any serious side effects and significantly reduced the severity of sleep apnea, indicating it is generally safe and well-tolerated. For sivopixant, treatment-related side effects were mild, with some patients experiencing changes in taste. Specific safety information for SASS-001 remains limited, as it is still under study. However, its progression to a Phase 2 trial suggests earlier studies deemed it safe enough for continued testing in people.

Overall, acetazolamide and sivopixant have shown to be fairly safe, with only mild side effects reported. SASS-001 is still being researched, but its advancement to this trial phase indicates it has met basic safety standards. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for sleep apnea because they offer novel approaches compared to standard therapies like CPAP machines and lifestyle changes. Sivopixant is unique because it targets the P2X3 receptor, potentially reducing the sensory nerve activity that contributes to sleep apnea. Acetazolamide acts differently by promoting breathing through its diuretic effect, which helps manage fluid retention that can worsen apnea. SASS-001 introduces a new compound that researchers believe may enhance sleep quality by addressing underlying biochemical pathways. Together, these treatments provide fresh perspectives in tackling sleep apnea beyond the typical mechanical or lifestyle interventions.

What evidence suggests that this trial's treatments could be effective for sleep apnea?

This trial will evaluate the effectiveness of Sivopixant, Acetazolamide, and SASS-001 for sleep apnea. Research has shown that Acetazolamide, which participants in this trial may receive, can effectively improve sleep apnea symptoms by reducing apnea events and maintaining better oxygen levels during sleep. Sivopixant, another treatment option in this trial, is under study for its potential to help with central sleep apnea, though detailed information from human studies remains limited. SASS-001, also under investigation, is a newer treatment being tested specifically for sleep apnea with a central component, but solid data on its effectiveness is not yet available. Overall, Acetazolamide has shown the most promising results so far, while Sivopixant and SASS-001 continue to be investigated for their potential benefits. ^{1 2 3 6 7}

Who Is on the Research Team?

Chief Scientific Officer

Principal Investigator

Shionogi Apnimed Sleep Science

Are You a Good Fit for This Trial?

Adults with sleep apnea, specifically those who have stopped or are non-compliant with PAP therapy, can join this trial. Participants should not be using any OSA devices for at least a week before the study and must have certain levels of oxygen desaturation and apnea-hypopnea index. Pregnant women, individuals with severe heart issues, uncontrolled psychiatric disorders, recent serious illnesses or infections, drug abuse history within 24 months, or on certain medications cannot participate.

Inclusion Criteria

OSA measures

AHI4 of > 10 to <60 events/h

My average oxygen levels drop frequently but not extremely low during sleep.

Exclusion Criteria

I have had breathing problems due to obesity or opioid use.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

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

17 days

Treatment Part B I

Participants receive acetazolamide oral tablets once daily at bedtime for 3 days

3 days

Treatment Part B II

Participants receive SASS-001 oral tablets once daily at bedtime for 10 days

10 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acetazolamide
• SASS-001
• Sivopixant

Trial Overview The trial is testing the effectiveness of three treatments: Sivopixant (a new medication), Acetazolamide (an existing diuretic), and SASS-001 against a placebo in adults with sleep apnea that includes central breathing interruptions during sleep.

How Is the Trial Designed?

Group I: Part B I: Acetazolamide Active Control 1 Intervention

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

Group II: Part B II: SASS-001 Active Control 1 Intervention

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

Group III: Part A: Sivopixant Active Control 1 Intervention

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

Group IV: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Shionogi Apnimed Sleep Science

Lead Sponsor

Trials

1

Recruited

60+

Published Research Related to This Trial

Acetazolamide has been established as the most effective medication for treating sleep apnea syndrome (SAS), outperforming other pharmacological options.

Other therapeutic approaches for SAS, including nasal CPAP, dental appliances, and surgeries, have not shown satisfactory effects when acetazolamide is not included in the treatment plan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug therapy for sleep apnea syndrome]. Takahashi, Y., Shimizu, T.[2013]

Acetazolamide (AZT) significantly improved sleep apnea symptoms in patients with high loop gain sleep apnea (HLGSA) both acutely and over a 3-month period, showing a notable reduction in the apnea hypopnea index (AHI) and breathing-related arousal index when combined with positive airway pressure (PAP) therapy.

The study involved 231 participants, with a strong predictor for treatment response being the non-rapid eye movement (NREM) AHI, indicating that AZT is a well-tolerated and effective option for managing HLGSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and long-term effects of acetazolamide in presumed high loop gain sleep apnea. Ni, YN., Holzer, RC., Thomas, RJ.[2023]

Acetazolamide significantly improves sleep apnea at high altitudes by reducing the Apnea-Hypopnea Index (AHI) and increasing nocturnal oxygenation, particularly in healthy trekkers compared to those with obstructive sleep apnea (OSA).

A daily dose of 250 mg of acetazolamide may be as effective as higher doses for healthy individuals, suggesting a potential optimal therapeutic dose for treating sleep apnea in high-altitude conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of acetazolamide on sleep apnea at high altitude: a systematic review and meta-analysis. Liu, HM., Chiang, IJ., Kuo, KN., et al.[2018]

In a study of 14 patients with central sleep apnea, low-dose acetazolamide (250 mg) significantly reduced the central apnea index (CAI) from 25.5 to 6.6 after one month of treatment, indicating its efficacy in managing central sleep apnea.

The treatment did not affect the obstructive apnea index (OAI) or total sleep time, but it did lead to a significant decrease in the number of arousals during sleep, suggesting improved sleep quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central apnea index decreases after prolonged treatment with acetazolamide. DeBacker, WA., Verbraecken, J., Willemen, M., et al.[2013]

In a study involving 45 patients with obstructive sleep apnea (OSA), acetazolamide significantly improved oxygen levels and reduced breathing disturbances at high altitudes compared to a placebo, indicating its potential as an alternative treatment when CPAP is not used.

Acetazolamide not only enhanced nocturnal oxygen saturation and reduced apnea/hypopnea indices but also improved sleep quality and prevented high blood pressure during altitude exposure, suggesting it stimulates ventilation effectively in OSA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with obstructive sleep apnea syndrome benefit from acetazolamide during an altitude sojourn: a randomized, placebo-controlled, double-blind trial. Nussbaumer-Ochsner, Y., Latshang, TD., Ulrich, S., et al.[2017]

In a study of 75 patients with sleep apnea syndrome, acetazolamide treatment significantly improved respiratory disorder variables, but only 45.3% of patients showed a meaningful reduction in their apnea hypopnea index (AHI).

Acetazolamide is most effective for mild cases of sleep apnea without obesity, while severe cases may benefit more from a combination of acetazolamide and uvulopalatopharyngoplasty.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and indication of acetazolamide treatment on sleep apnea syndrome. Inoue, Y., Takata, K., Sakamoto, I., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7768933/

Acetazolamide for OSA and Central Sleep Apnea Short-term acetazolamide improved both OSA and CSA. Rigorous studies with long-term follow up are warranted to assess Acetazolamide's value for the chronic ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1389945723001405

Acute and long-term effects of acetazolamide in presumed ... The effect of acetazolamide in reducing residual sleep apnea lasts at least 3 months. •. The apnea-hypopnea index during non-rapid eye movement sleep is a ...

3. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.9116

The role of acetazolamide in sleep apnea at sea level Only 1 study compared the results of ATZ and ATZ plus CPAP. This study showed that the usage of ATZ plus CPAP was more effective in improving AHI but not SpO2.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5941979/

The effect of acetazolamide on sleep apnea at high altitude Acetazolamide improves sleep apnea at high altitude by decreasing AHI and percentage of periodic breathing time and increasing nocturnal oxygenation.

5. atsjournals.org atsjournals.org/doi/full/10.1513/AnnalsATS.202204-366CC

Acetazolamide as an Adjunct to Positive Airway Pressure ... The studies indicate the presence of moderate obstructive-predominant sleep apnea, which improves after the addition of positive airway pressure.

6. atsjournals.org atsjournals.org/doi/full/10.1164/rccm.202109-2043OC

American Journal of Respiratory and Critical Care Medicine There were no serious adverse events. STM reduced the apnea–hypopnea index from 55.2 to 33.0 events/h (−41.0%) in the 400-mg group and from 61.1 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05616260

Acetazolamide for Obstructive Sleep Apnea to Improve ... Recent data suggest, that acetazolamide may help OSA patients to not choke in their sleep and lower their blood pressure. Especially young adults with OSA are ...