Overview
Sponsor-declared trial summary
Phase
Human pharmacology (Phase I) - Other
Status
Ended
Participants planned
24
Countries
1
Sites
1
NA, PD study in Healthy Volunteers
To evaluate the CNS PD response to brexanolone using TMS-induced MEPs compared to the responses of placebo and lorazepam.
Key facts
- Sponsor
- Sage Therapeutics Inc.
- Participant type
- Healthy volunteers
- Age range
- 18-64 years
- Gender
- Male
- Therapeutic area
- Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]
- Trial duration
- 11 May 2023 → 9 Oct 2023
- Decision date (initial)
- 2023-04-28
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Sage Therapeutics
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Dose response
To evaluate the CNS PD response to brexanolone using TMS-induced MEPs compared to the responses of placebo and lorazepam.
Secondary objectives 1
- To determine the effect of brexanolone compared to placebo and lorazepam in response to paired TMS pulses that capture intracortical circuitry modulation
Conditions and MedDRA coding
NA, PD study in Healthy Volunteers
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Participant is a healthy ambulatory male adult and has no clinically significant findings, as determined by the investigator, on physical examination, including neurologic and mental status examinations, 12-lead electrocardiogram (ECG), or laboratory tests.
- Participant is ≥18 and ≤65 years of age at the time informed consent is obtained.
- Participant has a body weight ≥50 kg and body mass index (BMI) ≥18.0 and ≤33.0 kg/m2 at screening.
Exclusion criteria 4
- Participant has a significant history or presence of psychiatric or neurologic disease or condition (including, but not limited to, epilepsy, closed head trauma with clinically significant sequelae, partial onset seizures, eating disorders, etc.).
- Participant has a history of intracranial mass lesion, hydrocephalus, and/or clinically significant head injury or trauma that could increase the risk of applying TMS.
- Participant has metal objects in the brain or skull or has a cochlear implant/deep brain stimulation device.
- Participant currently takes any psychotropic medications, including antidepressants and anxiolytics.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Change from baseline in TMS-MEPs amplitude obtained from single-pulse TMS-electromyography at T1
Secondary endpoints 3
- Change from baseline in magnitude of short-interval cortical inhibition obtained with paired-pulse TMS-electromyography at T1
- Change from baseline in magnitude of intracortical facilitation (ICF) obtained with paired pulse TMS-electromyography at T1
- Change from baseline in magnitude of long-interval cortical inhibition obtained with paired-pulse TMS-electromyography at T1
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
SUB192405 · Substance
- Active substance
- Brexanolone
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 90 µg/Kg microgram(s)/kilogram
- Max total dose
- 90 µg/Kg microgram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Lorazepam Aurobindo 1 mg, tabletten
PRD582288 · Product
- Active substance
- Lorazepam
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 2 mg milligram(s)
- Max total dose
- 2 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- N05BA06 — LORAZEPAM
- Marketing authorisation
- RVG 57547
- MA holder
- AUROBINDO PHARMA B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Overencapsulated
Placebo 2
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Sage Therapeutics Inc.
- Sponsor organisation
- Sage Therapeutics Inc.
- Address
- 215 1st Street Suite 220
- City
- Cambridge
- Postcode
- 02142-1213
- Country
- United States
Scientific contact point
- Organisation
- Sage Therapeutics Inc.
- Contact name
- Centre For Human Drug Research
Public contact point
- Organisation
- Sage Therapeutics Inc.
- Contact name
- Centre For Human Drug Research
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 24 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Centre for Human Drug Research
NA, Zernikedreef 8, 2333 CL, Leiden
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2023-05-11 | 2023-10-09 | 2023-05-22 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| Summary of Results SUM-50496
|
2024-10-09T10:44:48 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Summary of Results for Laypersons | 2024-10-09T10:45:48 | Submitted | Laypersons Summary of Results |
Documents 2 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | Summary of Results for Laypersons | 1 |
| Summary of results (for publication) | Summary of Results | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-03-20 | Netherlands | Acceptable 2023-04-28
|
2023-04-28 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2023-05-12 | Netherlands | Acceptable 2023-04-28
|
2023-05-12 |