Sivopixant + Acetazolamide + SASS-001 for Sleep Apnea

Recruiting at 3 trial locations

Overseen By Chief Scientific Officer, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Shionogi Apnimed Sleep Science

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

Disqualifiers: Heart failure, Stroke, COPD, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

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 the combination of Sivopixant, Acetazolamide, and SASS-001 safe for treating sleep apnea?

Acetazolamide has been studied for sleep apnea and is generally considered safe, though it may cause side effects like metabolic acidosis (a condition where the body produces too much acid or the kidneys do not remove enough acid). There is no specific safety data available for the combination of Sivopixant, Acetazolamide, and SASS-001. ^{1 2 3 4 5}

How is the drug combination of Sivopixant, Acetazolamide, and SASS-001 unique for treating sleep apnea?

This treatment is unique because it combines acetazolamide, which is already known to help with sleep apnea, especially in mild cases or at high altitudes, with two other components, Sivopixant and SASS-001, which may offer additional benefits or target different aspects of the condition, potentially improving overall effectiveness. ^{1 2 3 4 6}

Research Team

Chief Scientific Officer

Principal Investigator

Shionogi Apnimed Sleep Science

Eligibility Criteria

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

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

AHI4 of > 10 to <60 events/h

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

Trial Timeline

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

Treatment Details

Interventions

• Acetazolamide (Other)
• SASS-001 (Other)
• Sivopixant (Other)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Clinical efficacy and indication of acetazolamide treatment on sleep apnea syndrome. [2013]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Acute and long-term effects of acetazolamide in presumed high loop gain sleep apnea. [2023]

3. United States 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. [2017]

4. Japan pubmed.ncbi.nlm.nih.gov

[Drug therapy for sleep apnea syndrome]. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Central apnea index decreases after prolonged treatment with acetazolamide. [2013]

6. England pubmed.ncbi.nlm.nih.gov

The effect of acetazolamide on sleep apnea at high altitude: a systematic review and meta-analysis. [2018]