Lumateperone Monotherapy for the Treatment of Bipolar Depression Conducted Globally

• Sponsor: Intra-Cellular Therapies, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03249376
• Collaborator: (none)
• Enrollment: 381
• Locations: 47
• Arms: 2
• Actual Duration (Months): 15.1
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The study will evaluate the efficacy and safety of ITI-007 in a randomized, double-blind, parallel-group, placebo-controlled, multi-center study in patients diagnosed with Bipolar I or Bipolar II disorder having a major depressive episode.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Depression	Drug: Lumateperone; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 381 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of Lumateperone Monotherapy in the Treatment of Patients With Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder (Bipolar Depression) Conducted Globally
• Actual Study Start Date: Nov 27, 2017
• Actual Primary Completion Date: Mar 1, 2019
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lumateperone Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks	Drug: Lumateperone; Lumateperone 42 mg (ITI-007 60 mg tosylate); Other Names: ITI-007
Placebo Comparator: Placebo Placebo administered once daily every evening for 6 weeks	Other: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score [Baseline to Day 43]

   The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.

Secondary Outcome Measures

1. Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score [Baseline to Day 43]

   The Clinical Global Impression Scale, Bipolar version (CGI-BP-S) total score is a clinician-rated scale that measures the patient's current illness state on a 3 to 21 point scale where a higher score is associated with greater illness severity.. Each domain (depression, mania, and overall illness) is rated from 1 (not ill at all) to 7 (among the most extremely ill) and the 3 scores are added to obtain the total score.

2. Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score [Baseline to Day 43]

   The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 14 item patient self-reported questionnaire that assesses how satisfied a patient is, using a 5-point scale from 1-very poor to 5-very good.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Major Inclusion Criteria:

• male or female subjects of any race, ages 18-75 inclusive, with a clinical diagnosis of Bipolar I or Bipolar II disorder

• experiencing a current major depressive episode

• able to provide written informed consent

Major Exclusion Criteria:

• any female subject who is pregnant or breast-feeding

• any subject judged to be medically inappropriate for study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Site	Birmingham	Alabama	United States	35294
2	Clinical Site	Sherman Oaks	California	United States	91403
3	Clinical Site	Miami	Florida	United States	33133
4	Clinical Site	Orange City	Florida	United States	32763
5	Clinical Site	Atlanta	Georgia	United States	30322
6	Clinical Site	Decatur	Georgia	United States	30030
7	Clinical Site	Chicago	Illinois	United States	60612
8	Clinical Site	Joliet	Illinois	United States	60435
9	Clinical Site	Shreveport	Louisiana	United States	71101
10	Clinical Site	Saint Louis	Missouri	United States	63128
11	Clinical Site	Buffalo	New York	United States	14215
12	Clinical Site	Charlotte	North Carolina	United States	28211
13	Clinical Site	The Woodlands	Texas	United States	77381
14	Clinical Site	Bothell	Washington	United States	98011
15	Clinical Site	Burgas		Bulgaria
16	Clinical Site	Kardzhali		Bulgaria
17	Clinical Site	Lovech		Bulgaria
18	Clinical Site	Plovdiv		Bulgaria
19	Clinical Site	Ruse		Bulgaria
20	Clinical Site	Sofia		Bulgaria
21	Clinical Site	Targovishte		Bulgaria
22	Clinical Site	Tsarev Brod		Bulgaria
23	Clinical Site	Varna		Bulgaria
24	Clinical Site	Veliko Tarnovo		Bulgaria
25	Clinical Site	Barranquilla		Colombia
26	Clinical Site	Bello		Colombia
27	Clinical Site	Pereira		Colombia
28	Clinical Site	Ekaterinburg		Russian Federation
29	Clinical Site	Moscow		Russian Federation
30	Clinical Site	Nizhny Novgorod		Russian Federation
31	Clinical Site	Omsk		Russian Federation
32	Clinical Site	Saint Petersburg		Russian Federation
33	Clinical Site	Samara		Russian Federation
34	Clinical Site	Saratov		Russian Federation
35	Clinical Site	Tomsk		Russian Federation
36	Clinical Site	Belgrade		Serbia
37	Clinical Site	Kragujevac		Serbia
38	Clinical Site	Novi Sad		Serbia
39	Clinical Site	Ivano-Frankivs'k		Ukraine
40	Clinical Site	Kharkiv		Ukraine
41	Clinical Site	Kherson		Ukraine
42	Clinical Site	Lviv		Ukraine
43	Clinical Site	Odesa		Ukraine
44	Clinical Site	Poltava		Ukraine
45	Clinical Site	Smila		Ukraine
46	Clinical Site	Uzhgorod		Ukraine
47	Clinical Site	Vinnytsia		Ukraine

Sponsors and Collaborators

• Intra-Cellular Therapies, Inc.

Investigators

• Study Director: Susan Kozauer, MD, Intra-Cellular Therapies, Inc.

Study Documents (Full-Text)

• Study Protocol - Nov 5, 2018
• Statistical Analysis Plan - Jun 12, 2019

More Information

Publications

None provided.

• Responsible Party: Intra-Cellular Therapies, Inc.
• ClinicalTrials.gov Identifier: NCT03249376
• Other Study ID Numbers: ITI-007-404
• First Posted: Aug 15, 2017
• Last Update Posted: Jun 3, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Depression; Depressive Disorder; Bipolar Disorder

Study Results

Participant Flow

Arm/Group Title	Lumateperone	Placebo
Arm/Group Description	Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks Lumateperone: Lumateperone (ITI-007 60 mg tosylate)	Placebo administered once daily every evening for 6 weeks Placebo: Placebo
Period Title: Overall Study
STARTED	188	189
COMPLETED	167	166
NOT COMPLETED	21	23

Baseline Characteristics

Arm/Group Title	Lumateperone	Placebo	Total
Arm/Group Description	Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks Lumateperone: Lumateperone 42 mg (ITI-007 60 mg tosylate)	Placebo administered once daily every evening for 6 weeks Placebo: Placebo	Total of all reporting groups
Overall Participants	188	189	377
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.7 (14.09)	44.1 (12.87)	44.9 (13.50)
Sex: Female, Male (Count of Participants)
Female	99 52.7%	120 63.5%	219 58.1%
Male	89 47.3%	69 36.5%	158 41.9%
Race/Ethnicity, Customized (Count of Participants)
Caucasian/White	173 92%	171 90.5%	344 91.2%
Black or African American	14 7.4%	15 7.9%	29 7.7%
Asian	1 0.5%	0 0%	1 0.3%
Other	0 0%	3 1.6%	3 0.8%
Region of Enrollment (participants) [Number]
United States	51 27.1%	59 31.2%	110 29.2%
Ukraine	49 26.1%	38 20.1%	87 23.1%
Bulgaria	49 26.1%	43 22.8%	92 24.4%
Serbia	6 3.2%	13 6.9%	19 5%
Russia	32 17%	34 18%	66 17.5%
Colombia	1 0.5%	2 1.1%	3 0.8%
Montgomery-Asberg Depression Rating Scale (MADRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	30.8 (4.92)	30.2 (4.65)	30.5 (4.79)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Description	The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated 10 item scale to assess depressive symptoms. Each item is rated on a 7-point scale from 0-6. The total score ranges from 0 to 60 with a higher score indicating increased severity of depressive symptoms.
Time Frame	Baseline to Day 43

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.

Arm/Group Title	Lumateperone	Placebo
Arm/Group Description	Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks Lumateperone: Lumateperone 42 mg (ITI-007 60 mg tosylate)	Placebo administered once daily every evening for 6 weeks Placebo: Placebo
Measure Participants	188	188
Least Squares Mean (Standard Error) [score on a scale]	-16.70 (0.693)	-12.12 (0.677)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lumateperone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Effects Model for Repeated Measure
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-4.6
	Confidence Interval	(2-Sided) 95%; -6.34 to -2.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.89
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression Scale, Bipolar Version (CGI-BP-S) Total Score
Description	The Clinical Global Impression Scale, Bipolar version (CGI-BP-S) total score is a clinician-rated scale that measures the patient's current illness state on a 3 to 21 point scale where a higher score is associated with greater illness severity.. Each domain (depression, mania, and overall illness) is rated from 1 (not ill at all) to 7 (among the most extremely ill) and the 3 scores are added to obtain the total score.
Time Frame	Baseline to Day 43

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.

Arm/Group Title	Lumateperone	Placebo
Arm/Group Description	Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks Lumateperone: Lumateperone 42 mg (ITI-007 60 mg tosylate)	Placebo administered once daily every evening for 6 weeks Placebo: Placebo
Measure Participants	188	188
Least Squares Mean (Standard Error) [score on a scale]	-3.48 (0.170)	-2.54 (0.167)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lumateperone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Effects Model for Repeated Measure
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.37 to -0.51
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.22
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Percent Score
Description	The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 14 item patient self-reported questionnaire that assesses how satisfied a patient is, using a 5-point scale from 1-very poor to 5-very good.
Time Frame	Baseline to Day 43

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Set contains all randomized patients who received at least one dose of study medication and had a valid baseline (pre-dose) measurement and at least one valid post-baseline measurement of MADRS total score.

Arm/Group Title	Lumateperone	Placebo
Arm/Group Description	Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks Lumateperone: Lumateperone 42 mg (ITI-007 60 mg tosylate)	Placebo administered once daily every evening for 6 weeks Placebo: Placebo
Measure Participants	188	188
Least Squares Mean (Standard Error) [Percent Score]	19.4 (1.49)	14.9 (1.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lumateperone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95%; 1.42 to 7.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From signing ICF until end of study procedures (~10 weeks), including 6 weeks of double-blind treatment.
Arm/Group Title	Lumateperone		Placebo
Arm/Group Description	Lumateperone 42 mg (ITI-007 60 mg tosylate) administered once daily every evening for 6 weeks Lumateperone: Lumateperone 42 mg (ITI-007 60 mg tosylate)		Placebo administered once daily every evening for 6 weeks Placebo: Placebo
All Cause Mortality
	Lumateperone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/188 (0%)		0/189 (0%)
Serious Adverse Events
	Lumateperone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/188 (0.5%)		0/189 (0%)
Psychiatric disorders
Mania	1/188 (0.5%)	1	0/189 (0%)	0
Other (Not Including Serious) Adverse Events
	Lumateperone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/188 (30.9%)		31/189 (16.4%)
Gastrointestinal disorders
Nauseau	12/188 (6.4%)		4/189 (2.1%)
Nervous system disorders
Headache	33/188 (17.6%)		19/189 (10.1%)
Somnolence	16/188 (8.5%)		2/189 (1.1%)
Dizziness	9/188 (4.8%)		10/189 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.