Clinical trial NCT05645432: An Open-Label Study Evaluating Brexanolone in Adults With Tinnitus
Official title: An Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Brexanolone in the Treatment of Adult Participants With Tinnitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tinnitus
Keywords: Tinnitus
Lead sponsor: Sage Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-12-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAE)
timeFrame: Up to Day 15
Secondary outcomes:
measure: Change From Baseline (Observed Value) to Hour 6 of Infusion in Visual Analog Scale-Loudness (VAS-L) Ratings
timeFrame: Baseline; 0.5, 1, 2, 3, 4, 5, and 6 hours during brexanolone infusion on Day 1
measure: Change From Baseline (Model Based) to Hour 6 of Infusion in VAS-L Ratings
timeFrame: Baseline; 0.5, 1, 2, 3, 4, 5, and 6 hours during brexanolone infusion on Day 1
measure: Change From Baseline (Observed Value) to Hour 6 of Infusion in Visual Analog Scale-Annoyance (VAS-A) Ratings
timeFrame: Baseline; 0.5, 1, 2, 3, 4, 5, and 6 hours during brexanolone infusion on Day 1
measure: Change From Baseline (Model Based) to Hour 6 of Infusion in VAS-A Ratings
timeFrame: Baseline; 0.5, 1, 2, 3, 4, 5, and 6 hours during brexanolone infusion on Day 1
measure: Change From Baseline (Observed Value) to Post-infusion in VAS-L Ratings Measured Via Daily Diary Over Multiple Days
timeFrame: Baseline; Days 2, 3, 4, 5, 6, and 7 after brexanolone infusion given on Day 1
measure: Change From Baseline (Model Based) to Post-infusion in VAS-L Ratings Measured Via Daily Diary Over Multiple Days
timeFrame: Baseline; Days 2, 3, 4, 5, 6, and 7 after brexanolone infusion given on Day 1
measure: Change From Baseline (Observed Value) to Post-infusion in VAS-A Ratings Measured Via Daily Diary Over Multiple Days
timeFrame: Baseline; Days 2, 3, 4, 5, 6, and 7 after brexanolone infusion given on Day 1
measure: Change From Baseline (Model Based) to Post-infusion in VAS-A Ratings Measured Via Daily Diary Over Multiple Days
timeFrame: Baseline; Days 2, 3, 4, 5, 6, and 7 after brexanolone infusion given on Day 1
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Sage Investigational Site
state: Georgia
city: Iowa City
country: United States
facility: Sage Investigational Site
state: Iowa
Study officials:
References: