Silexan® in mild to moderate major depressive disorder

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dr. Willmar Schwabe GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

17 Nov 2025 → ongoing

Decision date (initial)

2025-10-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Dr. Willmar Schwabe GmbH & Co. KG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate superiority of 80 mg/day Silexan® once daily vs placebo with respect to the change of the Montgomery-Åsberg Depression Rating Scale (MADRS) total score between Baseline and Week 8 when treating Major Depressive Disorders (MDD) of mild to moderate severity, regardless of adherence to the treatment regime and under the hypothetical condition that treatments which ease depressive symptoms are not available for participants who discontinue from the randomised treatment.

If this can be shown, the superiority of 80 mg/day Silexan® compared to placebo should be demonstrated for treating MDD of mild depressive disorders based on the treatment effects described above.

In order to supplement the primary objective and to describe the clinical relevance of the findings, MADRS responder and remission rates are compared between Silexan® 80 mg/day and placebo for participants with MDD of mild to moderate severity and for participants with MDD of mild severity, regardless of adherence to the treatment regime and under the hypothetical condition that treatments which ease depressive symptoms are not available for participants who discontinue from the randomised treatment. Participants with a reduction of the MADRS total score of at least 50% between Baseline and Week 8 are responders, participants with an MADRS total score of less than 10 points at Week 8 are remitters.

Secondary objectives 2

1. Secondary objectives related to efficacy: To evaluate the impact of Silexan® compared to placebo on changes of depressive symptoms; to determine functional impairment and global improvement for patients with MDD of mild to moderate severity and for patients with MDD of mild severity, regardless of adherence to the treatment regime and under the hypothetical condition that treatments which ease depressive symptoms are not available for participants who discontinue from the randomized treatment.
2. Secondary objectives related to safety: To assess safety and tolerability of Silexan® compared to placebo when treating MDD of mild to moderate severity.

Conditions and MedDRA coding

Mild to moderate major depressive disorder

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age of at least 18 years.
2. Diagnosis of a major depressive episode according to ICD-10 (single episode: F32.0, 32.1, recurrent episode: F33.0, 33.1) of mild to moderate severity with a duration of at least 2 weeks but not longer than one year.
3. MADRS total score for the inclusion in the run-in and into the active treatment phase: 17–30.
4. Outpatient treatment by a general or specialised physician.
5. Body weight: Body Mass Index (BMI) between 18 and 35 kg/m2.
6. Written informed consent in accordance with the legal requirement.
7. Readiness and ability on the part of the participant to comply with the physician’s instructions and to fill in the self-assessment scales.

Exclusion criteria 20

1. Participation in a further clinical trial at the same time or in the last 12 weeks before screening.
2. History of hypersensitivity to lavender preparations and/or known allergies to the IMP, placebo or excipients.
3. Any unstable acute medical disorder or clinically relevant hepatic, renal, cardiovascular, respiratory, cerebrovascular, metabolic disorder or progressive diseases as cancer, haematologic diseases (including haemophilia, Christmas disease, von Willebrand’s disease, past medical history of bleeding gastric or duodenal ulcers or other significant bleeding disorders) or thyroid insufficiency (exception: non-insulin dependent diabetes mellitus, thyroid and anterior pituitary insufficiency on stable treatment), epilepsy or a history of seizure disorder or treatment with anticonvulsants for epilepsy or seizures, Parkinson’s disease.
4. Any somatic disease that necessitates regular treatment with systemic steroids.
5. Clinically significant abnormality of ECG and/or laboratory value(s) assessed at Screening Visit.
6. Any abnormal baseline finding considered by the investigator to be indicative of conditions that might affect trial results.
7. Positive pregnancy test during Visit 1.
8. Pregnancy, planning of pregnancy or lactation.
9. Persons capable of childbearing if not using highly effective contraception; these include: • Oral, intravaginal, transdermal combined (oestrogen and progestogen containing) hormonal contraception • Oral, injectable and implantable progestogen-only hormonal contraception • Intrauterine device • Intrauterine hormone-releasing system • Bilateral tubal occlusion • Vasectomised partner • Sexual abstinence (referring to heterosexual relationships)
10. Gastrointestinal disorders with uncertain absorption of orally administered drugs (e.g. partial or total gastrectomy, enterectomy, inflammatory bowel disease, celiac disease, symptomatic lactose intolerance, other disorders associated with chronic diarrhoea).
11. Unable to read, understand and/or complete questionnaires.
12. Diagnosis of MDD of severe severity as defined by ICD-10 (single episode: F32.2, recurrent episode: F33.2) or rating of the MADRS total score > 30 at screening or baseline visit.
13. History or suspicion of unreliability, poor cooperation or non-compliance with medical treatment.
14. Any clinically important psychiatric or neurological diagnoses according to ICD-10, other than trial indication, within 6 months before the trial such as: • Schizophrenia (F20.-), • Acute anxiety disorder (F41.-) • Episodes of depression with any characteristics of a psychotic nature (F32.3, F33.3), depressive disorders not defined as inclusion criteria (F34.1, F32.9), bipolar disorder (F31.-), cyclothymia (F34.0), mania (F30.-), • Organic, including symptomatic, mental disorders (F00-F09), • Post-traumatic stress disorder (F43.10), • Eating disorders (F50.-).
15. History or evidence of alcohol and/or substance abuse or dependence, particularly of sedatives, hypnotics and anxiolytics. (F10-F19).
16. Risk of suicide, or previous suicide attempt or clear display of auto-aggressive behaviour as defined (but not limited to) MADRS Item 10 “suicidal thoughts” score  2.
17. Lack of response to any adequate antidepressant therapy in the present episode of depression (adequate means  150 mg amitriptyline-equivalents per day or SSRI treatment during at least 6 weeks). Patients who are already well adjusted to an antidepressant therapy in the present episode may not be enrolled into this trial.
18. Any of the following treatments within 30 days before baseline visit: • Antidepressants • Depot neuroleptics • Monoamine oxidase (MAO) inhibitors •Pimozide •Benzodiazepines •Other psychotropic drugs •Intravenous methylene blue •Linezolid.
19. Unacceptability to discontinue or likelihood to need medication during the trial that is prohibited as concomitant treatment (see section 10.2). The following medication is not allowed during the trial: • Any psychotropic drugs including o benzodiazepines, tranquilizer, antidepressants, anxiolytics, antiepileptics, MAO inhibitors, pimozide, lamotrigine, linezolid, intravenous methylene blue o non-benzodiazepines (exception: ≤ 10 mg zolpidem/day for not longer than 10 days during the trial) o neuroleptics (exception: ≤ 75 mg melperone/day for not longer than 10 days during the trial). However, NO exception for zolpidem and for melperone is allowed within 5 days prior to any trial visit. • Long-term prophylactic treatment (e.g. lithium, carbamazepine) • Central-acting antihypertensive medication (guanethidine, guanoxan, clonidin, prazosine, α-methyldopa, reserpine) • Digoxin • Xanthine derivatives such as Theophylline • Antiparkinson medication • Phytopharmaceuticals with anxiolytic properties (e.g. hypericum extract, valerian extract) • Muscle relaxants • Analgesics of opiate type • Anaesthetics • Barbiturates • Nootropics • Coumarin derivates • Antibiotics
20. Non-medicinal psychiatric treatment during the last 2 weeks prior to baseline visit and during the course of the trial (e.g. standardised and digital psychotherapy, sleep withdrawal, phototherapy, electroconvulsive therapy, digital health applications [DiGAs]).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The change in MADRS total score between Baseline and Week 8.

Secondary endpoints 7

1. Efficacy endpoint: • Changes from Baseline in Clinical Global Impressions (CGI) (Item 1), Patient Health Questionnaire-9(PHQ-9) total score, Sheehan Disability Scale (SDS) total score at Week 8
2. Efficacy endpoint: • CGI (Item 2) at Week 8
3. Efficacy endpoint: • At least 50% reduction of MADRS total score between Baseline and Week 8 (responder)
4. Efficacy endpoint: • MADRS total score < 10 at Week 8 (remitter).
5. Safety endpoint:• Frequency of participants with at least one Adverse Event (AE),Adverse Drug Reaction (ADR), serious AE; number, type, severity and seriousness of AEs, and their relationship to the Investigational Medicinal Product (IMP); frequency of participants with AEs leading to withdrawal
6. Safety endpoint:• Evaluation of safety assessments (physical examination, vital signs, 12-lead electrocardiography (ECG), laboratory evaluation, concomitant medication, non-medicinal psychiatric treatment)
7. Safety endpoint:• Risk of suicide

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dr. Willmar Schwabe GmbH & Co. KG

Sponsor organisation

Dr. Willmar Schwabe GmbH & Co. KG

Address

Willmar-Schwabe-Strasse 4, Durlach Durlach

City

Karlsruhe

Postcode

76227

Country

Germany

Scientific contact point

Organisation

Dr. Willmar Schwabe GmbH & Co. KG

Contact name

Annette Waßmer

Public contact point

Organisation

Dr. Willmar Schwabe GmbH & Co. KG

Contact name

Annette Waßmer

Third parties 3

Locations

2 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications