A study to assess the efficacy and safety of lumateperone in patients with major depressive disorder

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intra-Cellular Therapies 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

10 Mar 2025 → ongoing

Decision date (initial)

2024-03-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Intra-Cellular Therapies, Inc. (USA)

External identifiers

EU CT number

2023-503836-41-00

ClinicalTrials.gov

NCT05850689

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Therapy

To evaluate the efficacy of lumateperone 42 mg administered once daily compared with placebo as adjunctive treatment to antidepressant therapy in patients with Major Depressive Disorder (MDD) who have an inadequate response to ongoing antidepressant therapy (ADT) as measured by change from baseline to Day 43 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.

Secondary objectives 9

1. Key secondary objective: To evaluate the efficacy of lumateperone 42 mg administered once daily compared with placebo as adjunctive treatment to ADT in patients with MDD who have an inadequate response to ongoing ADT as measured by change from baseline to Day 43 in the Clinical Global Impression Scale-Severity (CGI-S).
2. 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;
3. The proportion of remitters, where remission is defined as a MADRS total score ≤ 10 at Day 43;
4. By-visit change from baseline in the MADRS total score;
5. By-visit change from baseline in the HAM-A total score;
6. By-visit change from baseline in CGI-S score
7. Change from baseline in the Changes in Sexual Functioning Questionnaire-14 item version (CSFQ-14) total score at each assessment time point, including Day 43
8. Change from baseline in MADRS individual item scores at each assessment time point, including Day 43.
9. The safety objective of this study is to determine the safety and tolerability of lumateperone 42 mg administered orally once daily compared with that of placebo in patients with MDD who have an inadequate response to ongoing ADT as assessed by AEs; clinical laboratory results; vital sign measures; ECG results; suicidality as assessed by the C-SSRS; and extrapyramidal symptoms (EPS) as assessed by Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson Angus Scale (SAS).

Conditions and MedDRA coding

Major Depressive Disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Patient provides written informed consent before the initiation of any study-specific procedures;
2. Male or female patients between the ages of 18 and 65 years, inclusive;
3. 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
4. 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 b. fluoxetine c. paroxetine d. sertraline e. duloxetine f. levomilnacipran/milnacipran (if locally approved for MDD) g. venlafaxine/desvenlafaxine h. bupropion i. vilazodone j. vortioxetine

Exclusion criteria 6

1. 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;
2. 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;
3. The patient experiences a ≥ 25% decrease in the MADRS total score between Screening (Visit 1) and Baseline (Visit 2);
4. The patient experiences a ≥ 25% decrease in the QIDS-SR-16 total score between Screening (Visit 1) and Baseline (Visit 2);
5. 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;
6. The patient has a first MDE at age 60 years or older.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline (Visit 2) to Day 43 (Visit 8) in MADRS total score.

Secondary endpoints 9

1. Key secondary efficacy endpoint is the change from baseline to Day 43 in the CGI-S score.
2. 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;
3. The proportion of remitters, where remission is defined as a MADRS total score ≤ 10 at Day 43;
4. By-visit mean change from baseline in the MADRS total score;
5. By-visit mean change from baseline in the HAM-A total score;
6. By-visit mean change from baseline in the CSFQ-14 total score;
7. By-visit mean change from baseline in CGI-S score;
8. Change from baseline in MADRS individual item scores at each assessment time point, including Day 43;
9. Safety parameters (AEs, clinical laboratory, vital signs, ECG, and EPS (AIMS, BARS, and SAS) and C-SSRS scales)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intra-Cellular Therapies Inc.

Sponsor organisation

Intra-Cellular Therapies Inc.

Address

430 East 29th Street Suite 900

City

New York

Postcode

10016-8367

Country

United States

Scientific contact point

Organisation

Intra-Cellular Therapies Inc.

Contact name

ITI Clinical Trials

Public contact point

Organisation

Intra-Cellular Therapies Inc.

Contact name

ITI Clinical Trials

Third parties 8

Locations

4 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 3 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 183 files

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

Application history

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