Brexanolone for Tinnitus

No longer recruiting at 1 trial location

Overseen By Kemi Bankole, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Supernus Pharmaceuticals, Inc.

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called brexanolone, an intravenous drug, to determine its safety and tolerability for people with tinnitus, a condition characterized by hearing ringing or noise without an external source. Participants will receive a single, 6-hour IV infusion of brexanolone to observe its effects. The trial suits individuals who have experienced tinnitus for at least six months but less than ten years and who suffer from mild to severe distress. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that brexanolone is likely to be safe for humans?

Research has shown that brexanolone has been tested for safety in other conditions, such as postpartum depression. In these studies, most participants tolerated brexanolone well, with common side effects including sleepiness and dizziness.

For tinnitus, early results suggest that brexanolone might be safe when administered as a single 6-hour IV drip. Although these findings are encouraging, further research is necessary to confirm its safety for tinnitus. Prospective participants should consult a healthcare provider about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for tinnitus?

Brexanolone is unique because it offers a new approach to treating tinnitus by targeting the brain's GABA receptors, which play a crucial role in regulating neuronal activity. Unlike current treatments that primarily focus on masking the noise or providing coping strategies, brexanolone is administered through a single, continuous intravenous infusion, potentially offering rapid relief. Researchers are excited about brexanolone because it might provide a more direct and effective way to address the underlying neural dysfunction in tinnitus, rather than just managing symptoms.

What evidence suggests that brexanolone might be an effective treatment for tinnitus?

Research has shown that brexanolone, administered through an IV, might alleviate tinnitus symptoms. Tinnitus involves hearing ringing or buzzing without any external sound. Although brexanolone is already used for postpartum depression, its effectiveness for tinnitus is still under investigation in this trial. This treatment might work by influencing brain pathways linked to tinnitus. Early research suggests it could reduce the noise experienced by those with tinnitus. However, further studies are necessary to confirm its efficacy for this condition. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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?

Supernus Pharmaceuticals, Inc.

Lead Sponsor

Trials

49

Recruited

14,000+

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05645432

An Open-Label Study Evaluating Brexanolone in Adults ... The primary objective of this study is to evaluate the safety and tolerability of brexanolone in participants with tinnitus following a single 6-hour continuous ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05645432?term=ZULRESSO&viewType=Table&rank=4

An Open-Label Study Evaluating Brexanolone in Adults With ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

3. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1662226/full

An open-label, proof-of-mechanism trial evaluating a ... ... brexanolone, an intravenous formulation of allopregnanolone, may improve tinnitus symptomatology. Adults between 18 and 65 years of age with ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/217369Orig2s000IntegratedR.pdf

217369Orig2s000 - accessdata.fda.gov used to treat PPD, but efficacy data are limited and randomized controlled trials often showed lack of superiority compared to placebo or ...

5. withpower.com withpower.com/trial/phase-2-tinnitus-2-2023-4fa5b

Brexanolone for Tinnitus · Info for Participants 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. Show ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37280463/

Safety of Brexanolone in Adults with Postpartum Depression Results: Overall, 499 patients received brexanolone in this postmarketing surveillance analysis between June 2019 and December 2021 ( ...