LUMATEPERONE for Major depressive disorder

Inclusion criteria

• {"criterion_text":"- Patient provides written informed consent before the initiation of any study-specific procedures;"}
• {"criterion_text":"- Male or female patients between the ages of 18 and 65 years, inclusive;"}
• {"criterion_text":"- Meets DSM-5 criteria for MDD (MDD with psychotic features will be acceptable) as confirmed by the Investigator or Sponsor-approved rater using the modified Structured Clinical Interview for DSM-5, Clinical Trials Version (SCID-5-CT) and meets all of the following criteria: a. The start of the current major depressive episode (MDE) is at least 12 weeks but not more than 18 months prior to Screening (Visit 1); b. Has at least moderate severity of illness based on rater-administered MADRS total score ≥ 24 at Screening (Visit 1) and at Baseline (Visit 2); c. Has at least moderate severity of illness based on CGI-S score ≥ 4 at Screening (Visit 1) and at Baseline (Visit 2); d. Has a Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥ 14 at Screening (Visit 1) and at Baseline (Visit 2); e. Has sufficient history and medical record confirmation verifying the ADT and the current MDE is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning"}
• {"criterion_text":"- Currently having an inadequate response (less than 50% improvement) to 2 or more ADT’s in the current MDE as confirmed by the Investigator using the Antidepressant Treatment Response Questionnaire (ATRQ) and taking at least the minimum effective dose (per package insert) of one of the following antidepressants as monotherapy treatment for at least 6 weeks duration: a. citalopram/escitalopram \tb. fluoxetine \tc. paroxetine \td. sertraline \te. duloxetine \tf. levomilnacipran/milnacipran (if locally approved for MDD) \tg. venlafaxine/desvenlafaxine \th. bupropion \ti. vilazodone \tj. vortioxetine"}

Exclusion criteria

• {"criterion_text":"- Within the patient’s lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD, including: a. Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder; b. Bipolar Disorder;"}
• {"criterion_text":"- Within 6 months of Screening, has a confirmed DSM-5 psychiatric diagnosis other than MDD including: a. Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder as primary diagnoses. Note: Anxiety symptoms may be allowed if secondary to MDD, provided these symptoms do not require concurrent treatment; b. Eating disorder; c. Substance use disorders (excluding nicotine); d. Personality disorder of sufficient severity to have a major impact on the patient’s psychiatric status; e. Within 12 months of Screening, has had any other psychiatric condition (other than MDD) that has been the main focus of treatment;"}
• {"criterion_text":"- The patient experiences a ≥ 25% decrease in the MADRS total score between Screening (Visit 1) and Baseline (Visit 2);"}
• {"criterion_text":"- The patient experiences a ≥ 25% decrease in the QIDS-SR-16 total score between Screening (Visit 1) and Baseline (Visit 2);"}
• {"criterion_text":"- In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during participation in the study or: a. At Screening (Visit 1), the patient scores “yes” on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening, or at Baseline (Visit 2), the patient scores “yes” on Suicidal Ideation Items 4 or 5 since the Screening Visit; b. At Screening (Visit 1), the patient has had 1 or more suicide attempts within 2 years prior to Screening; c. At Screening (Visit 1) or Baseline (Visit 2), the patient scores ≥ 5 on MADRS Item 10 (Suicidal Thoughts), or d. The patient is considered to be in imminent danger to him/herself or others;"}
• {"criterion_text":"- The patient has a first MDE at age 60 years or older."}

Primary endpoints

• {"endpoint_text":"- Change from Baseline (Visit 2) to Day 43 (Visit 8) in MADRS total score.","definition_or_measurement_approach":"Change from baseline to Day 43 in the rater-administered Montgomery-Åsberg Depression Rating Scale (MADRS) total score."}

Secondary endpoints

• {"endpoint_text":"- Key secondary efficacy endpoint is the change from baseline to Day 43 in the CGI-S score.","definition_or_measurement_approach":"Change from baseline to Day 43 in the Clinical Global Impression Scale-Severity (CGI-S) score."}
• {"endpoint_text":"- The proportion of patients who are treatment responders where response is defined as a ≥ 50% decrease from baseline in MADRS total score at Day 43;","definition_or_measurement_approach":"Responder defined as ≥50% decrease from baseline in MADRS total score at Day 43; proportion of patients meeting this criterion."}
• {"endpoint_text":"- The proportion of remitters, where remission is defined as a MADRS total score ≤ 10 at Day 43;","definition_or_measurement_approach":"Remission defined as MADRS total score ≤ 10 at Day 43; proportion of patients meeting this criterion."}
• {"endpoint_text":"- By-visit mean change from baseline in the MADRS total score;","definition_or_measurement_approach":"Mean change from baseline in MADRS total score at each scheduled visit."}
• {"endpoint_text":"- By-visit mean change from baseline in the HAM-A total score;","definition_or_measurement_approach":"Mean change from baseline in Hamilton Anxiety Rating Scale (HAM-A) total score at each scheduled visit."}
• {"endpoint_text":"- By-visit mean change from baseline in the CSFQ-14 total score;","definition_or_measurement_approach":"Mean change from baseline in Changes in Sexual Functioning Questionnaire-14 item version (CSFQ-14) total score at each scheduled visit (including Day 43)."}
• {"endpoint_text":"- By-visit mean change from baseline in CGI-S score;","definition_or_measurement_approach":"Mean change from baseline in CGI-S score at each scheduled visit."}
• {"endpoint_text":"- Change from baseline in MADRS individual item scores at each assessment time point, including Day 43;","definition_or_measurement_approach":"Change from baseline in individual MADRS item scores at each assessment time point."}
• {"endpoint_text":"- Safety parameters (AEs, clinical laboratory, vital signs, ECG, and EPS (AIMS, BARS, and SAS) and C-SSRS scales)","definition_or_measurement_approach":"Safety assessments include adverse events, clinical laboratory results, vital signs, ECGs, suicidality assessed by the C-SSRS, and extrapyramidal symptoms assessed by AIMS, BARS, and SAS."}

Methods

• K1 Recruitment arrangements documents (country-specific K1 documents for Bulgaria, Spain, France, Lithuania) describing recruitment procedures.
• Patient brochures (country/language-specific: LT, RU, BG, ES, FR, EN titles present).
• Patient flyers (country/language-specific).
• Patient posters (country/language-specific).
• Outreach and Advertising materials (document titled 'Outreach and Advertising').
• Pre-screening website content (document titled 'Merged Bilingual Table of ePR Participant Journey' / 'Pre-screening Website Content').
• Referral Hub materials (document titled 'Merged Bilingual Table of Referral Hub').
• Telephone-based recruitment and scheduling using inbound/outbound call scripts, warm transfer call scripts, appointment scheduling call scripts, and cancellation scripts (multiple language versions, including Bulgarian).
• Email outreach (merged bilingual table of ePR participant journey emails).
• Patient welcome letters and patient ID cards (country/language-specific).

Lithuania

Earliest CTIS Part Ii Submission Date

28-02-2024

Latest Decision Or Authorization Date

26-01-2026

Processing Time Days

698

Number Of Sites

2

Number Of Participants

15

Spain

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

11-12-2025

Processing Time Days

653

Number Of Sites

5

Number Of Participants

20

France

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

16-12-2025

Processing Time Days

658

Number Of Sites

5

Number Of Participants

20

Bulgaria

Earliest CTIS Part Ii Submission Date

27-02-2024

Latest Decision Or Authorization Date

22-12-2025

Processing Time Days

664

Number Of Sites

10

Number Of Participants

100

Primary sponsor

Full Name

Intra-Cellular Therapies Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Catalent Germany Schorndorf GmbH

Responsibilities

14

Name

Q Squared Solutions Limited

Responsibilities

4

Name

Medidata Solutions Inc.

Responsibilities

7

Name

Iqvia Limited

Responsibilities

1,10,12,2,5,8

Name

Eresearchtechnology Inc.

Responsibilities

15 (Cardiac services)

Name

PPD Development LP

Responsibilities

4

Name

Propharma Group The Netherlands B.V.

Responsibilities

8

Name

Signant Health LLC

Responsibilities

15 (Scales/Questionnaires; Rater trainings/certification)

Third parties

• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Limited","duties_or_roles":"1,10,12,2,5,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"15 (Cardiac services)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Propharma Group The Netherlands B.V.","duties_or_roles":"8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"15 (Scales/Questionnaires; Rater trainings/certification)","organisation_type":"Pharmaceutical company"}