An Open-Label Study Evaluating Brexanolone in Adults With Tinnitus

• ClinicalTrials.gov Identifier: NCT05645432
• Recruitment Status: Completed
• First Posted: December 9, 2022
• Last Update Posted: December 22, 2023
• Sponsor: Sage Therapeutics
• Information provided by (Responsible Party): Sage Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Tinnitus	Drug: Brexanolone	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Brexanolone in the Treatment of Adult Participants With Tinnitus
• Actual Study Start Date: May 10, 2023
• Actual Primary Completion Date: November 21, 2023
• Actual Study Completion Date: November 21, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Brexanolone; Participants will receive a continuous, 6-hour IV infusion of Brexanolone on Day 1 of the Treatment Period.	Drug: Brexanolone; Brexanolone IV infusion; Other Names: Allopregnanolone; ZULRESSO®; SAGE-547

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events (TEAE) [ Time Frame: Up to approximately 7 days ]
   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. A TEAE is defined as an AE with onset after the start of investigational product (IP), or any worsening of a pre-existing medical condition/adverse event with onset after the start of IP and throughout the study.

Secondary Outcome Measures :

1. Change From Baseline to Hour 6 of Infusion in Visual Analog Scale-Loudness (VAS-L) Ratings [ Time Frame: Baseline, up to 6 hours of IP Infusion on Day 1 ]
   VAS-L is a subject-rated scale for evaluating tinnitus. Participants will answer the question "How loud is your tinnitus now?" on a horizontal scale anchored on left by "not audible" and on right by "extremely loud". Scoring for it will be assessed in a linear vertical scale, with the left side being not audible (score of 0) and the right side being extremely loud (score of 100).
2. Change From Baseline to Hour 6 of Infusion in Visual Analog Scale-Annoyance (VAS-A) Ratings [ Time Frame: Baseline, up to 6 hours of IP Infusion on Day 1 ]
   VAS-A is a subject-rated scale for evaluating tinnitus. Participants will answer the question "How much is your tinnitus annoying you now?" on a horizontal scale anchored on left by "not annoying" and on right by "extremely annoying". Scoring for it will be assessed in a linear vertical scale, with the left side being not annoying (score of 0) and the right side being extremely annoying (score of 100).
3. Change From Baseline to Post-infusion in VAS-L Ratings Measured via Daily Diary Over Multiple Days [ Time Frame: Baseline, up to approximately 6 days from Day 2 to Day 7 after IP infusion given on Day 1 ]
   VAS-L is a subject-rated scale for evaluating tinnitus. Participants will answer the question "How loud is your tinnitus now?" on a horizontal scale anchored on left by "not audible" and on right by "extremely loud" via daily diary over multiple days. Scoring for it will be assessed in a linear vertical scale, with the left side being not audible (score of 0) and the right side being extremely loud (score of 100).
4. Change From Baseline to Post-infusion in VAS-A Ratings Measured via Daily Diary Over Multiple Days [ Time Frame: Baseline, up to approximately 6 days from Day 2 to Day 7 after IP infusion given on Day 1 ]
   VAS-A is a subject-rated scale for evaluating tinnitus. Participants will answer the question "How much is your tinnitus annoying you now?" on a horizontal scale anchored on left by "not annoying" and on right by "extremely annoying" via daily diary over multiple days. Scoring for it will be assessed in a linear vertical scale, with the left side being not annoying (score of 0) and the right side being extremely annoying (score of 100).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Participant has a designated companion for the Clinic Treatment Visit who will drive them when they leave the clinic
2. 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
3. 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
4. Participant has mild to severe tinnitus distress according to Tinnitus Handicap Inventory (THI) score of 24 to 68 at Screening
5. 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

Exclusion Criteria:

1. 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
2. Participant has a history of sleep apnea or any clinically significant respiratory conditions that may predispose the participant to hypoxia during the infusion
3. 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
4. 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)
5. 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
6. 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
7. Participant has history of chronic otitis media (>3 per year during past 5 years)
8. Participant has a total score of 15 or greater (i.e., moderately severe) on the Patient Health Questionnaire-9 (PHQ-9) at Screening
9. 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
10. Participant has a known allergy to progesterone, allopregnanolone, or any IP excipient
11. 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
12. 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
13. 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
14. 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
15. 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
16. Participant is unable to complete participation in the study, e.g., due to preplanned event including elective surgery

Contacts and Locations

Locations

United States, Georgia

Sage Investigational Site

Atlanta, Georgia, United States, 30331

United States, Iowa

Sage Investigational Site

Iowa City, Iowa, United States, 52242

Sponsors and Collaborators

Sage Therapeutics

More Information

• Responsible Party: Sage Therapeutics
• ClinicalTrials.gov Identifier: NCT05645432
• Other Study ID Numbers: 547-TRM-201
• First Posted: December 9, 2022
• Last Update Posted: December 22, 2023
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sage Therapeutics:

Tinnitus

Additional relevant MeSH terms:

Tinnitus; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Pregnanolone; Brexanolone; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Neurosteroids; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Modulators; GABA Agents