A research study to compare the antidepressant ability and safety of Samyr® tablets versus placebo tablets as an adjunct to additional antidepressant treatment in patients with major depressive disorder (MDD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mylan Inc.

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

22 Mar 2024 → ongoing

Decision date (initial)

2024-10-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Mylan Inc.

External identifiers

EU CT number

2024-513019-29-00

EudraCT number

2017-003073-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate that in subjects with MDD with inadequate response to antidepressants and Hamilton score of 15-20 (with up to 10% reduction at baseline) Samyr® is superior to placebo tablet, when used along with an adjunctive antidepressant therapy following six weeks of treatment based on HDRS-17 score.

Secondary objectives 2

1. To evaluate the general improvement on the Patient Global Impression (PGI) scale and the Clinical Global Impression (CGI) scale following six weeks of treatment.
2. To evaluate the safety and tolerability of Samyr® tablet

Conditions and MedDRA coding

Major Depression Disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Written and signed informed consent needs to be provided by subject before starting any protocol-specific procedures.
2. Male and female subject between the ages of 18 to 65 years, both ages inclusive.
3. Subject who is able and willing to comply with the requirements of the study protocol including the visits scheme, assessments and scales.
4. Primary diagnosis of MDD of at least 12 weeks duration, according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and as confirmed by version 7.0 of the Mini International Neuropsychiatric Interview (MINI).
5. Subject is on prescribed SSRI (citalopram / escitalopram / sertraline / paroxetine / fluoxetine) or SNRI (venlafaxine / desvenlafaxine / duloxetine) antidepressant treatment, at approved and stable dose, for at least 4 weeks prior to screening that is insufficient/ineffective.
6. The subject is deemed to have inadequate response (less than 50% symptom reduction) to their current antidepressant based on the investigator judgment and the treatment history.
7. Subject who have a HDRS-17 score between 15-20 at screening. The baseline score must remain ≤20 and should not have >10% reduction between screening and baseline (randomization visit).

Exclusion criteria 20

1. History or presence of a medical condition or disease that in the Investigator’s opinion would place the subject at an unacceptable risk as a result of trial participation.
2. Any clinically significant abnormality in electrocardiogram (ECG) or safety laboratory tests that in the Investigator’s opinion would place the subject at an unacceptable risk as a result of trial participation.
3. Receipt of another investigational drug within 45 days prior to screening, or if the screening visit is within 5 half-lives of another investigational drug received (whichever is longer) or scheduled to receive another investigational drug during the current study period.
4. Any elective surgery requiring hospitalization planned during the study period.
5. Any lifetime history of bipolar disorders or psychotic disorders (other than MDD with psychotic features in a prior but not the current episode) as per the MINI.
6. History of drug abuse and/or marijuana use and/or alcohol dependence during the 3 years prior to screening.
7. The subject is, in the investigator’s opinion, at significant current risk of harming himself/herself, or provides the following answers on the C-SSRS at screening: - “Yes” to Question 4 or 5 on the Lifetime version Suicidal Ideation section and the ideation was within the last 3 months at Screening Visit, OR - “Yes” to question on the Lifetime version Suicidal Behavior section (other than preparatory behavior) and the ideation was within the last 3 months at Screening Visit.
8. Use of more than any 4 acceptable antidepressant treatments since the diagnosis of depression.
9. Previous treatment with Samyr which was not effective or resulted in an AE, or already treated with Samyr for the current episode.
10. Hypersensitivity to the active substance or to any of the excipients of Samyr or placebo (lactose).
11. Subjects with known genetic defects which affect the methionine cycle and/or cause homocystinuria and/or hyperhomocysteinaemia (e.g. cystathionine beta-synthase deficiency, defects of vitamin B12 metabolism).
12. Treatment with Monoamine Oxidase (MAO)-inhibitors including selegiline and moclobemide, during the 4 weeks prior to screening.
13. Treatment with linezolid or pimozide during the 4 weeks prior to screening; these must not be taken during study.
14. Treatment with prohibit medication prior to screening as detailed in Appendix 1.
15. Cardiac disorder which in the Investigator’s opinion would place the subject at an unacceptable risk from trial participation.
16. Known QT interval prolongation or congenital long QT syndrome.
17. Currently treatment with products that are known to prolong the QT interval.
18. Hepatic values that in the Investigator’s opinion would place the subject at an unacceptable risk as a result of trial participation.
19. Female subjects who are pregnant or breast-feeding or are planning to become pregnant during the study.
20. Female subjects of childbearing potential who are not able/willing to use oral contraception or acceptable methods of contraception as outlined in this protocol (Protocol Section 4.3), from the time of screening and for the duration of the study, through study completion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the change from baseline in the HDRS-17 score to visit 9 (Week 6).

Secondary endpoints 1

1. Change from baseline of the PGI and CGI scales after 6 weeks of treatment (visit 9).

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mylan Inc.

Sponsor organisation

Mylan Inc.

Address

1000 Mylan Boulevard

City

Canonsburg

Postcode

15317-5853

Country

United States

Scientific contact point

Organisation

Mylan Inc.

Contact name

EUClinicalTrials@Viatris

Public contact point

Organisation

Mylan Inc.

Contact name

EUClinicalTrials@Viatris

Third parties 7

Locations

1 EU/EEA country · 12 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 20 files

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

Application history

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