ADEMETIONINE for Major depressive disorder

Inclusion criteria

• {"criterion_text":"- Written and signed informed consent needs to be provided by subject before starting any protocol-specific procedures.\n- Male and female subject between the ages of 18 to 65 years, both ages inclusive.\n- Subject who is able and willing to comply with the requirements of the study protocol including the visits scheme, assessments and scales.\n- 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).\n- 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.\n- 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.\n- 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

• {"criterion_text":"- 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.\n- Hypersensitivity to the active substance or to any of the excipients of Samyr or placebo (lactose).\n- 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).\n- Treatment with Monoamine Oxidase (MAO)-inhibitors including selegiline and moclobemide, during the 4 weeks prior to screening.\n- Treatment with linezolid or pimozide during the 4 weeks prior to screening; these must not be taken during study.\n- Treatment with prohibit medication prior to screening as detailed in Appendix 1.\n- Cardiac disorder which in the Investigator’s opinion would place the subject at an unacceptable risk from trial participation.\n- Known QT interval prolongation or congenital long QT syndrome.\n- Currently treatment with products that are known to prolong the QT interval.\n- Hepatic values that in the Investigator’s opinion would place the subject at an unacceptable risk as a result of trial participation.\n- Female subjects who are pregnant or breast-feeding or are planning to become pregnant during the study.\n- 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.\n- 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.\n- 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.\n- Any elective surgery requiring hospitalization planned during the study period.\n- 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.\n- History of drug abuse and/or marijuana use and/or alcohol dependence during the 3 years prior to screening.\n- 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.\n- Use of more than any 4 acceptable antidepressant treatments since the diagnosis of depression.\n- Previous treatment with Samyr which was not effective or resulted in an AE, or already treated with Samyr for the current episode."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is the change from baseline in the HDRS-17 score to visit 9 (Week 6).","definition_or_measurement_approach":"Change from baseline in HDRS-17 score to visit 9 (Week 6); measured using the HDRS-17 (Hamilton Depression Rating Scale) score at baseline and at Week 6."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline of the PGI and CGI scales after 6 weeks of treatment (visit 9).","definition_or_measurement_approach":"Change from baseline on the Patient Global Impression (PGI) and Clinical Global Impression (CGI) scales at Week 6 (visit 9)."}

Methods

• K1_Recruitment arrangement and supporting materials referenced in CTIS (document titles present): Recruitment Brochure, Promotional Flyer, Study Poster, Patient Letter — patient-facing materials for potential participants.
• HCP-targeted materials present in CTIS: HCP Factsheet and HCP Letter — healthcare professional outreach channel to refer or inform eligible patients.
• Recruitment materials (K2 and K1 documents) explicitly listed in CTIS associated with the Italy Part II submission; target audience explicitly includes patients and HCPs (country of conduct: Italy).

Italy

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

602

Number Of Sites

12

Number Of Participants

600

Primary sponsor

Full Name

Mylan Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

ClinChoice, Inc.

Responsibilities

codes: 1,10,11,12,13,14,2,5,6,7,8,9

Name

Icon Clinical Research Limited

Responsibilities

codes: 2,3,4

Third parties

• {"country":"Netherlands","full_name":"Certe Medische Diagnostiek en Advies Stichting","duties_or_roles":"Specialty Lab – Vitamin B6","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Italy","full_name":"Cromsource S.r.l.","duties_or_roles":"codes: 1,10,12,13,14,2,5,6,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Other - IP supply, management & destruction; IVRS/IRT","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Medical Equipment Supplies And Management Limited","duties_or_roles":"Ancillary supplies e.g ECG & Thermometer","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"ClinChoice, Inc.","duties_or_roles":"codes: 1,10,11,12,13,14,2,5,6,7,8,9","organisation_type":"Industry"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"codes: 2,3,4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"EDC","organisation_type":"Non-Pharmaceutical company"}