An Open-Label Study Evaluating Brexanolone in Adults With Tinnitus

NCT05645432 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 547-TRM-201
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

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 intravenous (IV) infusion.

Conditions

Tinnitus

Keywords

Tinnitus

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAE)

  An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal (investigational) product. A TEAE is defined as an AE with onset after the start of brexanolone, or any worsening of a pre-existing medical condition/adverse event with onset after the start of brexanolone and throughout the study.

  Up to Day 15

Secondary Outcomes (8)

• Change From Baseline (Observed Value) to Hour 6 of Infusion in Visual Analog Scale-Loudness (VAS-L) Ratings

  Baseline; 0.5, 1, 2, 3, 4, 5, and 6 hours during brexanolone infusion on Day 1

• Change From Baseline (Model Based) to Hour 6 of Infusion in VAS-L Ratings

  Baseline; 0.5, 1, 2, 3, 4, 5, and 6 hours during brexanolone infusion on Day 1

• Change From Baseline (Observed Value) to Hour 6 of Infusion in Visual Analog Scale-Annoyance (VAS-A) Ratings

  Baseline; 0.5, 1, 2, 3, 4, 5, and 6 hours during brexanolone infusion on Day 1

• Change From Baseline (Model Based) to Hour 6 of Infusion in VAS-A Ratings

  Baseline; 0.5, 1, 2, 3, 4, 5, and 6 hours during brexanolone infusion on Day 1

• Change From Baseline (Observed Value) to Post-infusion in VAS-L Ratings Measured Via Daily Diary Over Multiple Days

  Baseline; Days 2, 3, 4, 5, 6, and 7 after brexanolone infusion given on Day 1

Study Arms (1)

Brexanolone

EXPERIMENTAL

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.

Drug: Brexanolone

Interventions

Brexanolone DRUG

Brexanolone IV infusion

Also known as: Allopregnanolone, ZULRESSO®, SAGE-547

Brexanolone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has a designated companion for the Clinic Treatment Visit who will drive them when they leave the clinic
• 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
• Participant has a diagnosis of subjective, idiopathic, unilateral or bilateral, non-pulsatile tinnitus (e.g., not due to medical disease) of ≥6 months and \<10 years duration
• Participant has mild to severe tinnitus distress according to Tinnitus Handicap Inventory (THI) score of 24 to 68 at Screening
• Participant is willing and able to safely discontinue the use of central nervous system (CNS) depressants (e.g., opioids and benzodiazepines), antidepressants, anticonvulsants, CNS stimulants (with the exception of caffeine), aspirin, other nonsteroidal anti inflammatory drugs, and aminoglycosides at least 14 days or 5 half-lives (whichever is longer) prior to receiving IP and through completion of the study

You may not qualify if:

• Participant has history or presence of any neurologic disease or condition, including, but not limited to, unexplained loss of consciousness, seizure disorder including a prior nonfebrile seizure, and closed head trauma with clinically significant sequelae
• Participant has a history of sleep apnea or any clinically significant respiratory conditions that may predispose the participant to hypoxia during the infusion
• Participant intends to start or discontinue a pharmacological or nonpharmacological therapy (e.g., psychotherapy, sound therapy, masking, transcranial magnetic stimulation \[TMS\]) for tinnitus during the course of the study
• Participant has currently active and medically significant or uncontrolled hepatic, renal, cardiovascular, pulmonary, gastrointestinal, hematological, immunologic, metabolic disease (hypothyroidism with stable thyroid replacement is acceptable)
• Participant's tinnitus can be modulated by maneuvers of the temporomandibular joint, head and neck, eyes, or limbs, or otherwise attributed to somatosensory cause or has had prior otoscopic surgeries or cholesteatoma
• Participants has current unilateral or bilateral hearing loss of 30 decibel (dB) or greater (mild hearing loss) in one or more tested frequencies (500 Hertz \[Hz\], 1000 Hz, 2000 Hz, and 4000 Hz), 60 dB or greater at 6000 Hz and 8000 Hz, asymmetry of 30 dB or greater in two or more tested frequencies, or uses a cochlear implant or hearing aid
• Participant has history of chronic otitis media (\>3 per year during past 5 years)
• Participant has a total score of 15 or greater (i.e., moderately severe) on the Patient Health Questionnaire-9 (PHQ-9) at Screening
• Participant has diagnosis of moderate or severe substance use disorder (excluding nicotine dependence) within 12 months of Screening, has a positive screen for drugs of abuse including tetrahydrocannabinol (THC) on Day 1 prior to dosing, or has a positive screen for alcohol on Day 1 prior to dosing
• Participant has a known allergy to progesterone, allopregnanolone, or any IP excipient
• 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
• Participant has a history of suicidal behavior within 2 years or answers "YES" to Questions 3, 4, or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or at Day 1 or is currently at risk of suicide in the opinion of the investigator
• Participant has donated 1 or more units (1 unit = 450 milliliter \[mL\]) of blood or experienced acute loss of an equivalent amount of blood within 60 days prior to Day 1
• Participant has any condition, comorbidity, or lifestyle consideration that in the opinion of the investigator would limit or interfere with the participant's ability to complete or partake in the study
• Participant is unwilling or unable to comply with study procedures and the required training during the Baseline Period. The participant must complete 10 VAS assessments remotely prior to Day 1

Sponsors & Collaborators

• Supernus Pharmaceuticals, Inc.: lead

Study Sites (2)

Sage Investigational Site

Atlanta, Georgia, 30331, United States

Location

Sage Investigational Site

Iowa City, Iowa, 52242, United States

Location

Related Publications (1)

• Watson LS, O'Donnell P, Bankole K, Toubouti Y, Tyler RS, Johannesen JK. An open-label, proof-of-mechanism trial evaluating a neuroactive steroid GABA modulator in tinnitus. Front Neurol. 2025 Nov 18;16:1662226. doi: 10.3389/fneur.2025.1662226. eCollection 2025.

  PMID: 41341514 DERIVED

MeSH Terms

Conditions

Tinnitus

Interventions

brexanolone; Pregnanolone

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Medical Monitor
• Organization: Sage Therapeutics

info@sagerx.com

(617) 299-8380

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2022
• First Posted: December 9, 2022
• Study Start: May 10, 2023
• Primary Completion: November 21, 2023
• Study Completion: November 21, 2023
• Last Updated: September 15, 2025
• Results First Posted: December 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)