Brexanolone for Tinnitus

Recruiting at 1 trial location

Overseen By Kemi Bankole, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sage Therapeutics

Must not be taking: CNS depressants, Antidepressants, Anticonvulsants, others

Disqualifiers: Neurologic disease, Sleep apnea, Hearing loss, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called brexanolone to see if it is safe for people who have tinnitus, a condition where they hear ringing in their ears.

Do I have to stop taking my current medications for the trial?

Yes, you will need to stop taking certain medications like CNS depressants, antidepressants, anticonvulsants, CNS stimulants (except caffeine), aspirin, and other nonsteroidal anti-inflammatory drugs at least 14 days or 5 half-lives before the study and until it is completed.

How is the drug brexanolone unique for treating tinnitus?

Brexanolone is unique because it is an intravenous drug that acts as a neuroactive steroid modulating GABAA receptors, which is different from typical oral medications for tinnitus. It was originally developed for postpartum depression, highlighting its novel mechanism of action in potentially treating tinnitus. ^{1 2 3 4 5}

Eligibility Criteria

Adults with tinnitus for 6 months to less than 10 years, experiencing mild to severe distress but in good physical health. They must not have significant medical conditions or allergies related to the treatment, and be able to stop certain medications before and during the trial. A companion is required for clinic visits.

Inclusion Criteria

Participant is in good physical health and has no clinically significant findings (excluding tinnitus), as determined by the investigator on medical history and physical examination, including neurologic and mental status examinations, 12-lead electrocardiogram (ECG), or clinical laboratory tests

You have been experiencing ringing in your ears for at least 6 months but less than 10 years.

You have mild to severe distress from ringing in your ears, as measured by a special test.

Exclusion Criteria

You have a serious and uncontrolled health condition affecting your liver, kidneys, heart, lungs, stomach, blood, immune system, or metabolism. If you have stable treatment for an underactive thyroid, you can still participate.

You are allergic to progesterone, allopregnanolone, or any ingredients in the study medication.

Participant has had exposure to another investigational drug or device within 30 days or 5 half-lives of the investigational drug, whichever is longer, prior to the Day 1 visit

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive a 6-hour single continuous intravenous (IV) infusion of brexanolone

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

14 days

Remote assessments on Days 2 through 7

Treatment Details

Interventions

• Brexanolone

Trial Overview The safety and tolerability of a single continuous intravenous infusion of brexanolone over 6 hours are being tested on adults with tinnitus to see if it can help reduce their symptoms.

Participant Groups

Group I: Brexanolone Experimental Treatment 1 Intervention

Participants will receive a 6-hour single continuous intravenous (IV) infusion of brexanolone at 30 micrograms per kilogram per hour (mcg/kg/hour) for 0 to 0.5 hours, at 60 mcg/kg/hour for 0.5 to 1 hour, and at 90 mcg/kg/hour for 1 to 6 hours, on Day 1 of the Treatment Period.

Brexanolone is already approved in United States for the following indications:

Approved in United States as Zulresso for:

• Postpartum Depression

Who Is Running the Clinical Trial?

Sage Therapeutics

Lead Sponsor

Trials

51

Recruited

11,000+

Founded

2010

Headquarters

Cambridge, USA

Known For

Brain Health Medicines

Top Products

ZURZUVAE (zuranolone), SAGE-324

Findings from Research

Brexanolone (ZULRESSO™) is an intravenously administered treatment specifically designed for postpartum depression (PPD), acting as a positive allosteric modulator of GABAA receptors, which helps enhance inhibitory neurotransmission in the brain.

Approved in March 2019, brexanolone is a formulation that combines allopregnanolone, a natural neurosteroid, with a solubilizing agent, marking a significant advancement in the treatment options available for adult women suffering from PPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone: First Global Approval. Scott, LJ.[2020]

Brexanolone (Zulresso) is an effective new treatment for postpartum depression (PPD), showing significant reductions in depression scores compared to placebo in clinical trials, particularly at doses of 60 and 90 μg/kg/hour.

While brexanolone has promising efficacy, it carries risks of somnolence and loss of consciousness, necessitating a Risk Evaluation and Mitigation Strategies (REMS) program to ensure patient safety during its administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone for Postpartum Depression: Clinical Evidence and Practical Considerations. Leader, LD., O'Connell, M., VandenBerg, A.[2020]

A pharmacovigilance study identified 267 cases of adverse drug reactions (ADRs) associated with brexanolone, with a significant number of reports related to psychiatric and nervous system issues, indicating a need for further investigation into these effects.

Serious outcomes were reported in 11.61% of patients using brexanolone, highlighting potential safety concerns that warrant additional prospective research to clarify the drug's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety profile of brexanolone: a pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS). Zhang, M., Xie, W., Li, J., et al.[2023]

Researchers developed new prodrugs of brexanolone, which is a synthetic version of a natural compound that helps modulate brain receptors related to mood regulation.

These prodrugs were shown to effectively release brexanolone both in laboratory tests and in living organisms, suggesting they could provide a longer-lasting treatment option for conditions like depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, synthesis and characterizations of prodrugs of brexanolone. Xu, L., Ma, J., Shi, L., et al.[2023]

Zulresso (brexanolone) is the only FDA-approved treatment for postpartum depression (PPD) and works by stimulating specific GABAA receptors in the brain, but its long infusion time and high cost can be barriers to use.

The study suggests that barbiturates and pyrazolopyridines, which also target the same GABAA receptors, could be repurposed as safer and more cost-effective alternatives for treating PPD, despite concerns about dependence with barbiturates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Barbiturates and pyrazolopyridines for the treatment of postpartum depression-repurposing of two drug classes. Horwitz, AB., Rubin, RT.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Brexanolone: First Global Approval. [2020]

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

Brexanolone for Postpartum Depression: Clinical Evidence and Practical Considerations. [2020]

3. Austria pubmed.ncbi.nlm.nih.gov

Postmarketing safety profile of brexanolone: a pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS). [2023]

4. England pubmed.ncbi.nlm.nih.gov

Design, synthesis and characterizations of prodrugs of brexanolone. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Barbiturates and pyrazolopyridines for the treatment of postpartum depression-repurposing of two drug classes. [2023]