A study to evaluate Samyr effectiveness and safety profile. The study is done by comparing that Samyr injection is better than placebo injection in subjects with depression which are treated regularly with antidepressant tablet treatment.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mylan Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

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

Trial duration

9 Jan 2019 → ongoing

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Mylan Inc.

External identifiers

EU CT number

2024-513022-29-00

EudraCT number

2017-003074-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate that Samyr IM is superior to placebo IM as an enhancer adjunctive to antidepressant therapy. The primary endpoint is the change from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) score after 7 days of treatment (visit 13).

Secondary objectives 3

1. MADRS change from baseline at scheduled visits.
2. HRDS-6 (Per-Bech) change from baseline at scheduled visits
3. Change in CGI and PGI from baseline at scheduled visits.

Conditions and MedDRA coding

Major Depression Disorders

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Written and signed informed consent needs to be provided by participant before starting any protocol-specific procedures.
2. Male and female participant between the ages of 18 to 65 years, both ages inclusive.
3. Participant 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), criteria.
5. Participant is on prescribed SSRI (citalopram / escitalopram / sertraline / paroxetine) or SNRI (venlafaxine / duloxetine) antidepressant treatment, at approved and stable dose (based on local SmPC), for at least 4 weeks prior to screening.
6. Partial-response to the prescribed antidepressant during the last 8 weeks prior to screening. Partial response is defined as less than 50% symptom reduction based on the investigator judgment and the treatment history.
7. Participant who have a Montgomery-Asberg Depression Rating Scale (MADRS) score as assessed by the site investigator of at least 22 at screening and with less than 15% reduction at baseline, post run in treatment. Additionally, participant must have a MADRS score of ≥19 at randomization.

Exclusion criteria 21

1. History or presence of a medical condition or disease that in the Investigator’s opinion would place the participant at an unacceptable risk as a result of trial participation.
2. Hypersensitivity to the active substance or to any of the excipients of Samyr.
3. Participant 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).
4. Treatment with Monoamine Oxidase (MAO)-inhibitors including selegiline and moclobemide, during the 4 weeks prior to screening.
5. Treatment with linezolid or pimozide.
6. Treatment with at least one prohibited medication as detailed in appendix 1 (prohibit drug medication prior and during the study).
7. Cardiac disorder which in the Investigator’s opinion would place the participant at an unacceptable risk from trial participation.
8. Known QT interval prolongation or congenital long QT syndrome.
9. Treatment with products that are known to prolong the QT interval.
10. Hepatic values that in the Investigator’s opinion would place the participant at an unacceptable risk as a result of trial participation.
11. Decrease in the baseline MADRS score by ≥ 15% vs screening visit.
12. Any clinically significant abnormality in electrocardiogram (ECG) or safety laboratory tests that in the Investigator’s opinion would place the participant at an unacceptable risk as a result of trial participation.
13. Female participant who are pregnant or plan to be pregnant or breast-feeding.
14. Female participant 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.
15. 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.
16. Any elective surgery requiring hospitalization planned during the study period.
17. History of bipolar disorders, Schizophrenia and other psychotic disorders.
18. Substance abuse or dependence.
19. The participant 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, OR - “Yes” to Questions 4 or 5 on the Since Last Visit version of the Suicidal Ideation section at the Baseline Visit - “Yes” to any question on the Suicidal Behavior section at the Baseline Visit.
20. Use of more than 4 acceptable antidepressant treatments since the diagnosis of depression or treatment with ECT or ketamine during the current episode or lifetime treatment with Vagus Nerve Stimulation (VNS) during the last 5 years.
21. Previous treatment with Samyr which was not effective or resulted in an AE, or already treatment with Samyr during the current episode.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in the MADRS score after 7 days of treatment (visit 13).

Secondary endpoints 3

1. MADRS change from baseline at scheduled visits.
2. HRDS-6 (Per-Bech) change from baseline at scheduled visits.
3. Change in CGI and PGI from baseline at scheduled visits.

Investigational products

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

Test 1

Placebo 2

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 9

Locations

1 EU/EEA country · 3 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 15 files

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

Application history

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