ADEMETIONINE for Major depressive disorder

Inclusion criteria

• {"criterion_text":"- Written and signed informed consent needs to be provided by participant before starting any protocol-specific procedures.\n- Male and female participant between the ages of 18 to 65 years, both ages inclusive.\n- Participant 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), criteria.\n- 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.\n- 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.\n- 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

• {"criterion_text":"- 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.\n- Hepatic values that in the Investigator’s opinion would place the participant at an unacceptable risk as a result of trial participation.\n- Decrease in the baseline MADRS score by ≥ 15% vs screening visit.\n- 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.\n- Female participant who are pregnant or plan to be pregnant or breast-feeding.\n- 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.\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- History of bipolar disorders, Schizophrenia and other psychotic disorders.\n- Substance abuse or dependence.\n- 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.\n- Hypersensitivity to the active substance or to any of the excipients of Samyr.\n- 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.\n- Previous treatment with Samyr which was not effective or resulted in an AE, or already treatment with Samyr during the current episode.\n- 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).\n- Treatment with Monoamine Oxidase (MAO)-inhibitors including selegiline and moclobemide, during the 4 weeks prior to screening.\n- Treatment with linezolid or pimozide.\n- Treatment with at least one prohibited medication as detailed in appendix 1 (prohibit drug medication prior and during the study).\n- Cardiac disorder which in the Investigator’s opinion would place the participant at an unacceptable risk from trial participation.\n- Known QT interval prolongation or congenital long QT syndrome.\n- Treatment with products that are known to prolong the QT interval."}

Primary endpoints

• {"endpoint_text":"- Change from baseline in the MADRS score after 7 days of treatment (visit 13).","definition_or_measurement_approach":"Change from baseline measured by the Montgomery-Asberg Depression Rating Scale (MADRS) at Day 7 (visit 13)."}

Secondary endpoints

• {"endpoint_text":"- MADRS change from baseline at scheduled visits.","definition_or_measurement_approach":"Change from baseline measured by MADRS at scheduled visits."}
• {"endpoint_text":"- HRDS-6 (Per-Bech) change from baseline at scheduled visits.","definition_or_measurement_approach":"Change from baseline measured by HRDS-6 (Per-Bech) at scheduled visits."}
• {"endpoint_text":"- Change in CGI and PGI from baseline at scheduled visits.","definition_or_measurement_approach":"Change from baseline measured by Clinical Global Impression (CGI) and Patient Global Impression (PGI) at scheduled visits."}

Italy

Earliest CTIS Part Ii Submission Date

20-08-2024

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

615

Number Of Sites

3

Number Of Participants

468

Primary sponsor

Full Name

Mylan Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Almac Clinical Services Limited

Responsibilities

IP packaging, labelling, QP release, supply, management & destruction; IVRS/IRT

Name

Icon Clinical Research Limited

Responsibilities

Codes: 2,4

Name

Cromsource S.r.l.

Responsibilities

Codes: 1,10,12,13,14,2,5,6,8,9

Name

ClinChoice, Inc.

Responsibilities

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

Third parties

• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"IP packaging, labelling, QP release, supply, management & destruction; IVRS/IRT","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Certe Medische Diagnostiek en Advies Stichting","duties_or_roles":"Specialty Lab – Vitamin : +31634205226","organisation_type":"Laboratory/Research/Testing facility"}
• {"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":"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":"Massachusetts General Hospital","duties_or_roles":"Patient validation for SAFER, MADRS & MGH ATRQ via CTNI remote assessment Rater training & surveillance","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Codes: 2,4","organisation_type":"Pharmaceutical company"}
• {"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 States","full_name":"Medidata Solutions Inc.","duties_or_roles":"EDC","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"Code: 3","organisation_type":"Pharmaceutical company"}