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Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Lumateperone for the Prevention of Relapse in Patients with Schizophrenia

Summary
EudraCT number	2021-002068-30
Trial protocol	BG PL
Global end of trial date	07 Aug 2024

Results information
Results version number	v1(current)
This version publication date	14 Nov 2025
First version publication date	14 Nov 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

ITI-007-304

ISRCTN number

US NCT number

NCT04959032

WHO universal trial number (UTN)

Sponsor organisation name

Intra-Cellular Therapies, Inc.

Sponsor organisation address

135 US 202/206, Suite 6, Bedminster, NJ, United States, 07921

Public contact

ITI Clinical Trials, Intra-Cellular Therapies. Inc., +1 6464409333, ITClclinicaltrials@itci-inc.com

Scientific contact

ITI Clinical Trials, Intra-Cellular Therapies. Inc., +1 6464409333, ITClclinicaltrials@itci-inc.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

29 Oct 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

07 Aug 2024

Global end of trial reached?

Yes

Global end of trial date

07 Aug 2024

Was the trial ended prematurely?

Main objective of the trial

•To evaluate the efficacy and safety of lumateperone relative to placebo in the prevention of relapse of symptoms in patients with schizophrenia.

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

Evidence for comparator

Actual start date of recruitment

08 Jul 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 24

Country: Number of subjects enrolled

Bulgaria: 115

Country: Number of subjects enrolled

Serbia: 71

Country: Number of subjects enrolled

United States: 382

Worldwide total number of subjects

592

EEA total number of subjects

139

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

592

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

The Screening phase begins once the Informed Consent Form is signed. Patients are evaluated during the screening period lasting up to 1 week.

Number of subjects started

866 ^[1]

Number of subjects completed

592

Reason: Number of subjects

Screen Failure: 274

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 are screened. Worldwide number are those subjects that were enrolled into the first phase of the study (open-label treatment phase).

Period 1 title

Open-Label Treatment Phase

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Open-Label Lumateperone 42 mg

Arm description

Arm type

Open-label Run-in and Stabilization Phase

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

Number of subjects in period 1	Open-Label Lumateperone 42 mg
Started	592
Completed	228
Not completed	364
Adverse event, serious fatal	1
Consent withdrawn by subject	104
inability to identify a caregiver; incarceration	2
Adverse event, non-fatal	54
Lost to follow-up	46
Lack of efficacy	122
Protocol deviation	35

Period 2 title

Double-blind Treatment Phase

Is this the baseline period?

Yes ^[2]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Lumateperone 42 mg

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

Placebo

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

Notes
[2] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: As this is a randomized withdrawal study design, subjects were required to start taking open-label study drug and meet stability criteria prior to being randomized into the double-blind treatment phase. The primary efficacy analysis is based on subjects in the double-blind treatment phase (Period 2); therefore, the baseline period is in period 2.

Number of subjects in period 2 ^[3] ^[4]	Lumateperone 42 mg	Placebo
Started	110	114
Completed	94	98
Not completed	16	16
Consent withdrawn by subject	9	8
Adverse event, non-fatal	2	2
Pregnancy	-	1
Lost to follow-up	2	3
Protocol deviation	3	2

Notes
[3] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The worldwide number represents all of the subjects that were enrolled into the first phase of the study (open-label treatment phase). As this is a randomized withdrawal study design, those subjects from the open-label treatment period who met stability criteria were then randomized into the double-blind treatment phase where the baseline period is included and for which the primary analysis is based on.
[4] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: 228 subjects completed the open-label treatment phase and were randomized into the double-blind treatment phase. Four subjects did not take study drug; therefore, only 224 subjects are included in the double-blind Safety/ITT population used for analysis.

Baseline characteristics

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Reporting group title

Lumateperone 42 mg

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group values	Lumateperone 42 mg	Placebo	Total
Number of subjects	110	114	224
Age categorical
Units: Subjects
Adults (18-64 years)	110	114	224
From 65-84 years	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	44.9 ( 9.75 )	45.4 ( 9.74 )	-
Gender categorical
Units: Subjects
Female	37	44	81
Male	73	70	143

End points

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Reporting group title

Open-Label Lumateperone 42 mg

Reporting group description

Reporting group title

Lumateperone 42 mg

Reporting group description

Reporting group title

Placebo

Reporting group description

Subject analysis set title

Double-blind ITT Population

Subject analysis set type

Intention-to-treat

Subject analysis set description

Double-blind Intent-to Treat Population includes all patients who were randomized into the Double-blind Treatment Period (DBTP) and took at least 1 dose of randomized study drug during the DBTP.

Primary: Time to First Symptom Relapse During the Double-blind Treatment Phase

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End point title

Time to First Symptom Relapse During the Double-blind Treatment Phase

End point description

9999=25th percentile and its upper limit of the 95% confidence interval were not estimable due to the low number of relapse events.

End point type

Primary

End point timeframe

Number of days from the randomization date to the first relapse date up to 26 weeks.

End point values	Lumateperone 42 mg	Placebo
Number of subjects analysed	110	114
Units: Days
number (confidence interval 95%)	9999 (159 to 9999)	43 (30 to 71)

Primary Efficacy

Comparison groups

Lumateperone 42 mg v Placebo

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.22

upper limit

0.65

Adverse events

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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 name

MedDRA

Dictionary version

24.0

Reporting group title

Open-label Treatment Phase

Reporting group description

Reporting group title

Double-blind Treatment Phase: Lumateperone 42 mg

Reporting group description

Reporting group title

Double-blind Treatment Phase: Placebo

Reporting group description

Serious adverse events	Open-label Treatment Phase	Double-blind Treatment Phase: Lumateperone 42 mg	Double-blind Treatment Phase: Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	23 / 592 (3.89%)	1 / 110 (0.91%)	7 / 114 (6.14%)
number of deaths (all causes)	1	0	0
number of deaths resulting from adverse events	1	0	0
Injury, poisoning and procedural complications
Muscle injury
subjects affected / exposed	0 / 592 (0.00%)	0 / 110 (0.00%)	1 / 114 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Intestinal obstruction
subjects affected / exposed	1 / 592 (0.17%)	0 / 110 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Acute psychosis
subjects affected / exposed	1 / 592 (0.17%)	0 / 110 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychotic disorder
subjects affected / exposed	7 / 592 (1.18%)	0 / 110 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Schizophrenia
subjects affected / exposed	9 / 592 (1.52%)	1 / 110 (0.91%)	6 / 114 (5.26%)
occurrences causally related to treatment / all	2 / 9	0 / 1	4 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	3 / 592 (0.51%)	0 / 110 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Completed suicide
subjects affected / exposed	1 / 592 (0.17%)	0 / 110 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 592 (0.00%)	0 / 110 (0.00%)	1 / 114 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19
subjects affected / exposed	1 / 592 (0.17%)	0 / 110 (0.00%)	0 / 114 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Open-label Treatment Phase	Double-blind Treatment Phase: Lumateperone 42 mg	Double-blind Treatment Phase: Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	85 / 592 (14.36%)	9 / 110 (8.18%)	10 / 114 (8.77%)
Nervous system disorders
Headache
subjects affected / exposed	78 / 592 (13.18%)	9 / 110 (8.18%)	4 / 114 (3.51%)
occurrences all number	84	11	4
Psychiatric disorders
Schizophrenia
subjects affected / exposed	9 / 592 (1.52%)	0 / 110 (0.00%)	6 / 114 (5.26%)
occurrences all number	10	0	9

More information

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Were there any global substantial amendments to the protocol? Yes

10 Mar 2021

-Corrected Inclusion Criterion 8 to reflect that PANSS positive symptom ratings were to be ≥ 4 -Corrected Exclusion Criterion 24 to reflect that hemoglobin exclusion criterion was < 8 mg/dL for females and ≤ 9 mg/dL for males and ANC exclusion was < 1200 cells/μL (1.2 × 109/L) -Clarified the list of prohibited medications -Clarified the first and third relapse criteria during the DBTP.

23 May 2022

-Added allowance for remote study visits at all visits except for Screening (Visit 1), Baseline (Visit 2), and Randomization (Visit 14) -Clarified eligibility for the DBTP, specifying that a 20% or greater decrease from baseline in PANSS total score was to be maintained from Visit 8 [beginning of SP] through Visit 14 [end of Week 18]) -Clarified content of study drug kits -Removed propoxyphene from substances listed for UDS test -Modified the primary efficacy analysis to: Remove the baseline PANSS total score from the Cox proportional hazard model and to specify the use of 3 graphical methods supportive of the Cox proportional hazards model assumption; Specify use of the Kaplan-Meier for the cumulative distribution function of time to relapse. The proportion of relapse-free patients at Week 26 would be provided using the product limit estimator, with associated CIs based on Greenwood’s formula and linear transformation; Specify that the treatment difference in proportion of relapse-free patients at Week 26 and associated confidence interval would be provided.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Lumateperone for the Prevention of Relapse in Patients with Schizophrenia

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Time to First Symptom Relapse During the Double-blind Treatment Phase

Primary: Time to First Symptom Relapse During the Double-blind Treatment Phase

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Lumateperone for the Prevention of Relapse in Patients with Schizophrenia

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Time to First Symptom Relapse During the Double-blind Treatment Phase

Primary: Time to First Symptom Relapse During the Double-blind Treatment Phase

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Lumateperone for the Prevention of Relapse in Patients with Schizophrenia