Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44365   clinical trials with a EudraCT protocol, of which   7389   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled Multicenter Study to Assess the Efficacy and Safety of Lumateperone as Adjunctive Therapy in the Treatment of Patients with Major Depressive Disorder

    Summary
    EudraCT number
    		 2021-001192-17
    Trial protocol
    		 CZ   SK   BG   HU  
    Global end of trial date
    27 Feb 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Nov 2025
    First version publication date
    13 Nov 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ITI-007-501
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04985942
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Intra-Cellular Therapies, Inc.
    Sponsor organisation address
    135 Route 202/206, Suite 6, Bedminster, NJ, United States, 07921
    Public contact
    ITI Clinical Trials, Intra-Cellular Therapies, Inc., +1 646-440-9333, ITCIClinicalTrials@itci-inc.com
    Scientific contact
    ITI Clinical Trials, Intra-Cellular Therapies, Inc., +1 646-440-9333, ITCIClinicalTrials@itci-inc.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 Apr 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Feb 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Feb 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of lumateperone 42 mg administered once daily compared with placebo as adjunctive treatment to antidepressant therapy in subjects 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.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles that have their origins in the Declaration of Helsinki. The study complied with the ICH Guidance on General Considerations for Clinical Trials and GCP, as well as CFR Part 312.
    Background therapy
    		 In order to meet eligibility criteria subjects must have had an inadequate response (less than 50% improvement) to one of the antidepressant therapies listed below as monotherapy treatment; having taken at least the minimum effective dose (per package insert) for at least 6 weeks duration. Patients would need to continue taking the antidepressant therapy throughout the 6 week double-blind treatment period: 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
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Jul 2021
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 151
    Country: Number of subjects enrolled
    Slovakia: 39
    Country: Number of subjects enrolled
    Bulgaria: 109
    Country: Number of subjects enrolled
    Czechia: 105
    Country: Number of subjects enrolled
    Hungary: 16
    Country: Number of subjects enrolled
    India: 65
    Worldwide total number of subjects
    485
    EEA total number of subjects
    269
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    478
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The Screening phase begins once the Informed Consent Form is signed. Subjects are evaluated during the screening period lasting up to 2 weeks.

    Pre-assignment period milestones
    Number of subjects started
    		 700 [1]
    Number of subjects completed
    		 485

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Screen Failure: 215
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Pre-assignment period includes all subjects that were screened. Worldwide number enrolled are those subjects that were randomized.
    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Lumateperone 42 mg + ADT
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lumateperone
    Investigational medicinal product code
    Other name
    ITI-007
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Lumateperone 42 mg once daily oral administration

    Arm title
    		 Placebo + ADT
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo capsule once daily oral administration

    Number of subjects in period 1
    		Lumateperone 42 mg + ADT Placebo + ADT
    Started
    242
    243
    Completed
    220
    232
    Not completed
    22
    11
         Consent withdrawn by subject
    5
    4
         Adverse event, non-fatal
    14
    2
         Lost to follow-up
    2
    1
         Protocol deviation
    1
    1
         Lack of efficacy
    -
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Lumateperone 42 mg + ADT
    Reporting group description
    		 -

    Reporting group title
    Placebo + ADT
    Reporting group description
    		 -

    Reporting group values
    		 Lumateperone 42 mg + ADT Placebo + ADT Total
    Number of subjects
    		 242 243 485
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 237 241 478
        From 65-84 years
    		 5 2 7
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 44.9 ( 12.42 ) 45.1 ( 12.51 ) -
    Gender categorical
    Units: Subjects
        Female
    		 159 160 319
        Male
    		 83 83 166

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Lumateperone 42 mg + ADT
    Reporting group description
    		 -

    Reporting group title
    Placebo + ADT
    Reporting group description
    		 -

    Subject analysis set title
    mITT
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Modified Intent-to-Treat (mITT) Population includes all randomized subjects who received at least one dose of study drug and have a baseline MADRS total score, and who have at least one on-study drug, postbaseline MADRS total score.

    Primary: Change from baseline to Day 43 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score

    		 Close Top of page
    End point title
    		 Change from baseline to Day 43 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score
    End point description
    End point type
    Primary
    End point timeframe
    Baseline to Day 43
    End point values
    		 Lumateperone 42 mg + ADT Placebo + ADT
    Number of subjects analysed
    239
    242
    Units: MADRS Total Score
        least squares mean (confidence interval 95%)
    -14.7 (-15.77 to -13.63)
    -9.8 (-10.83 to -8.74)
    Statistical analysis title
    		 Primary Efficacy Analysis
    Comparison groups
    Lumateperone 42 mg + ADT v Placebo + ADT
    Number of subjects included in analysis
    481
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed Effects Model for Repeated Measure
    Parameter type
    		 LS Mean Difference
    Point estimate
    -4.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.38
         upper limit
    		 -3.44
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.75

    Secondary: Change from baseline to Day 43 in the Clinical Global Impression-Severity Scale (CGI-S) total score

    		 Close Top of page
    End point title
    		 Change from baseline to Day 43 in the Clinical Global Impression-Severity Scale (CGI-S) total score
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to Day 43
    End point values
    		 Lumateperone 42 mg + ADT Placebo + ADT
    Number of subjects analysed
    239
    242
    Units: CGI-S Total Score
        least squares mean (confidence interval 95%)
    -1.6 (-1.74 to -1.47)
    -0.9 (-1.07 to -0.80)
    Statistical analysis title
    		 Key Secondary Efficacy Analysis
    Comparison groups
    Lumateperone 42 mg + ADT v Placebo + ADT
    Number of subjects included in analysis
    481
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed Effects Model for Repeated Measure
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.85
         upper limit
    		 -0.48
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the time the subject gives study-specific informed consent until the end of study procedures being completed.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Lumateperone 42 mg + ADT
    Reporting group description
    		 Includes subjects randomized to the Lumateperone 42 mg + ADT group and who received at least 1 dose of study drug.

    Reporting group title
    Placebo + ADT
    Reporting group description
    		 Includes subjects randomized to the Placebo + ADT group and who received at least 1 dose of study drug.

    Serious adverse events
    		 Lumateperone 42 mg + ADT Placebo + ADT
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 241 (0.41%)
    1 / 243 (0.41%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Joint dislocation
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 243 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 243 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Lumateperone 42 mg + ADT Placebo + ADT
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    92 / 241 (38.17%)
    53 / 243 (21.81%)
    Nervous system disorders
    Tremor
         subjects affected / exposed
    12 / 241 (4.98%)
    1 / 243 (0.41%)
         occurrences all number
    13
    1
    Headache
         subjects affected / exposed
    38 / 241 (15.77%)
    37 / 243 (15.23%)
         occurrences all number
    50
    31
    Dizziness
         subjects affected / exposed
    25 / 241 (10.37%)
    15 / 243 (6.17%)
         occurrences all number
    27
    19
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    23 / 241 (9.54%)
    5 / 243 (2.06%)
         occurrences all number
    24
    6
    Gastrointestinal disorders
    Dry Mouth
         subjects affected / exposed
    26 / 241 (10.79%)
    5 / 243 (2.06%)
         occurrences all number
    26
    5
    Nausea
         subjects affected / exposed
    12 / 241 (4.98%)
    10 / 243 (4.12%)
         occurrences all number
    12
    12

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Jun 2021
    Inclusion Criterion #2 was revised to lower maximum age of study eligibility from 75 years to 65 years; Inclusion Criterion #4 was modified to add ATRQ for confirmation of inadequate response to ADT by the Investigator; Removed “moderate CYP3A4 inhibitors” from prohibited medications; Clarified time period for AE and SAE reporting; Added estimand strategy for primary and key secondary efficacy objectives, revised analyses of primary, key secondary, and additional efficacy parameters to accommodate estimand strategy, and updated analysis populations.
    20 Aug 2021
    Exclusion Criterion #21e was modified to specify exclusion of patients with moderate or severe hepatic impairment; Added study stopping criteria; Added additional analyses of the primary efficacy parameter.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue Dec 09 22:05:14 CET 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA