An Open-Label Study Evaluating Brexanolone in Adults With Tinnitus

An Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Brexanolone in the Treatment of Adult Participants With Tinnitus

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05645432

Enrollment

Registered

2022-12-09

Start date

2023-05-10

Completion date

2023-11-21

Last updated

2025-09-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Tinnitus

Keywords

Tinnitus

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.

Interventions

DRUGBrexanolone

Brexanolone IV infusion

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-Emergent Adverse Events (TEAE)	Up to Day 15	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.

Secondary

Measure	Time frame	Description
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	VAS-L is a subject-rated scale used to assess the perceived loudness of tinnitus. Participants answered the question How loud is your tinnitus now? on a horizontal scale anchored on left by not audible (score of 0) and on right by extremely loud (score of 100). Higher scores represent greater severity. Negative change from baseline represents better outcome of the treatment. A Mixed Model Repeated Measures (MMRM) with fixed effects for baseline VAS component value and change from baseline scores as the dependent variable is used. For the treatment period (Day 1), baseline was defined as the most recent value immediately prior to the start of brexanolone infusion, or predose.
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	VAS-A is a subject-rated scale used to assess the tinnitus. Participants answered the question How much is your tinnitus annoying you now? on a horizontal scale anchored on the left by not annoying (score of 0) and on the right by extremely annoying (score of 100). Higher scores represent greater severity. Negative change from baseline represents better outcome of the treatment. For the treatment period (Day 1), baseline was defined as the most recent value immediately prior to the start of brexanolone infusion, or predose.
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	VAS-A is a subject-rated scale used to assess the tinnitus. Participants answered the question How much is your tinnitus annoying you now? on a horizontal scale anchored on the left by not annoying (score of 0) and on the right by extremely annoying (score of 100). Higher scores represent greater severity. Negative change from baseline represents better outcome of the treatment. A MMRM with fixed effects for baseline VAS component value and change from baseline scores as the dependent variable is used. For the treatment period (Day 1), baseline was defined as the most recent value immediately prior to the start of brexanolone infusion, or predose.
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	VAS-L is a subject-rated scale used to assess the perceived loudness of tinnitus. Participants answered the question How loud is your tinnitus now? on a horizontal scale anchored on left by not audible (score of 0) and on right by extremely loud (score of 100). Higher scores represent greater severity. Negative change from baseline represents better outcome of the treatment. For the treatment period (Day 1), baseline was defined as the most recent value immediately prior to the start of brexanolone infusion, or predose.
Change From Baseline (Model Based) 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	VAS-L is subject-rated scale used to assess perceived loudness of tinnitus. Participants answered question How loud is your tinnitus now? on horizontal scale anchored on left by not audible (score of 0) and on right by extremely loud (score of 100) via daily diary over multiple days. Higher scores= greater severity. Negative change from baseline= better outcome of treatment. For remote assessments (Day 2 through 7), ratings were obtained twice daily (morning and evening). Daily arithmetic mean was calculated by averaging morning and evening scores. If a participant was missing either a morning or evening score, then single available score was used as the mean for that day. A MMRM with fixed effects for baseline VAS component value and change from baseline scores as the dependent variable is used. Baseline is defined as the average value of Day -7 to Day -1 measurements. This was calculated by summing daily arithmetic means and dividing by total number of non-missing days.
Change From Baseline (Observed Value) to Post-infusion in VAS-A Ratings Measured Via Daily Diary Over Multiple Days	Baseline; Days 2, 3, 4, 5, 6, and 7 after brexanolone infusion given on Day 1	VAS-A is subject-rated scale used to assess the tinnitus. Participants answered the question How much is your tinnitus annoying you now? on horizontal scale anchored on left by not annoying (score of 0) and on right by extremely annoying (score of 100) via daily diary over multiple days. Higher scores=greater severity. Negative change from baseline=better outcome of treatment. For remote assessments (Day 2 through 7), ratings were obtained twice daily (morning and evening). Daily arithmetic mean was calculated by averaging morning and evening scores. If a participant was missing either a morning or evening score, then single available score was used as the mean for that day. Baseline is defined as the average value of Day -7 to Day -1 measurements. This was calculated by summing daily arithmetic means and dividing by total number of non-missing days.
Change From Baseline (Model Based) to Post-infusion in VAS-A Ratings Measured Via Daily Diary Over Multiple Days	Baseline; Days 2, 3, 4, 5, 6, and 7 after brexanolone infusion given on Day 1	VAS-A is subject-rated scale used to assess the tinnitus. Participants answered the question How much is your tinnitus annoying you now? on horizontal scale anchored on left by not annoying (score of 0) and on right by extremely annoying (score of 100) via daily diary over multiple days. Higher scores=greater severity. Negative change from baseline=better outcome of treatment. For remote assessments (Day 2 through 7), ratings were obtained twice daily (morning and evening). Daily arithmetic mean was calculated by averaging morning and evening scores. If a participant was missing either a morning or evening score, then single available score was used as the mean for that day. A MMRM with fixed effects for baseline VAS component value and change from baseline scores as the dependent variable is used. Baseline is defined as the average value of Day -7 to Day -1 measurements. This was calculated by summing daily arithmetic means and dividing by total number of non-missing days.
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	VAS-L is subject-rated scale used to assess perceived loudness of tinnitus. Participants answered question How loud is your tinnitus now? on horizontal scale anchored on left by not audible (score of 0) and on right by extremely loud (score of 100) via daily diary over multiple days. Higher scores= greater severity. Negative change from baseline= better outcome of treatment. For remote assessments (Day 2 through 7), ratings were obtained twice daily (morning and evening). Daily arithmetic mean was calculated by averaging morning and evening scores. If a participant was missing either a morning or evening score, then single available score was used as the mean for that day. Baseline is defined as the average value of Day -7 to Day -1 measurements. This was calculated by summing daily arithmetic means and dividing by total number of non-missing days.

Countries

United States

Participant flow

Recruitment details

Participants were enrolled at one active clinical site in the United States from 10 May 2023 to 21 November 2023.

Pre-assignment details

A total of 29 participants were screened, of which 10 were enrolled and treated.

Participants by arm

Arm	Count
Brexanolone Participants received a 6-hour single continuous IV infusion of brexanolone at 30 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.	10
Total	10

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Brexanolone
Age, Continuous	48.8 years STANDARD_DEVIATION 9.96
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	6 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	4 Participants
Sex: Female, Male Female	7 Participants
Sex: Female, Male Male	3 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 10
other Total, other adverse events	1 / 10
serious Total, serious adverse events	0 / 10

Outcome results

Primary

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.

Time frame: Up to Day 15

Population: Safety set included all participants who received any amount of brexanolone.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Brexanolone	Number of Participants With Treatment-Emergent Adverse Events (TEAE)	1 Participants

Secondary

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

VAS-A is a subject-rated scale used to assess the tinnitus. Participants answered the question How much is your tinnitus annoying you now? on a horizontal scale anchored on the left by not annoying (score of 0) and on the right by extremely annoying (score of 100). Higher scores represent greater severity. Negative change from baseline represents better outcome of the treatment. A MMRM with fixed effects for baseline VAS component value and change from baseline scores as the dependent variable is used. For the treatment period (Day 1), baseline was defined as the most recent value immediately prior to the start of brexanolone infusion, or predose.

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