Lurasidone - A 6-week Study of Patients With Bipolar I Depression (Add-on)

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00868452
• Collaborator: (none)
• Enrollment: 348
• Locations: 71
• Arms: 2
• Duration (Months): 33
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This clinical study is designed to test the hypothesis that lurasidone is effective, tolerable, and safe when added to treatment with lithium or Divalproex for the treatment of patients with bipolar I depression.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Depression	Drug: lurasidone + (lithium or divalproex); Drug: Placebo + (lithium or divalproex)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 348 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, 6-Week, Double-Blind, Placebo- Controlled, Flexible-Dose, Parallel-Group Study of Lurasidone Adjunctive to Lithium or Divalproex for the Treatment of Bipolar I Depression
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lurasidone	Drug: lurasidone + (lithium or divalproex); lurasidone 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7.
Placebo Comparator: Placebo	Drug: Placebo + (lithium or divalproex); 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6) [Baseline, Week 6]

   MADRS total score ranges from a minimum of 0 to a maximum of 60. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening.

Secondary Outcome Measures

1. Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) [Baseline Week 6]

   CGI-EP-S depression score ranges from a minimum of 0 to a maximum of 7. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening.

2. Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score [Baselin Week 6]

   STS total score ranges from a minimum of 0 to a maximum of 30. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subject is diagnosed with bipolar I disorder, most resent episode depressed

• Subject must have a lifetime history of at least one bipolar manic or mixed episode

• Subject must be taking lithium or divalproex at least 28 days prior to screening

Exclusion Criteria:

• History of nonresponse to an adequate (6-week) trial of three or more antidepressants (with or without mood stabilizers) during the current episode

• Subject has been hospitalized for a manic or mixed episode within 60 days prior to randomization

• Imminent risk of suicide or injury to self, others, or property

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Woodland International Research Inc.	Little Rock	Arkansas	United States	72211
2	South Coast Clinical Trials, Inc.	Anaheim	California	United States	92804
3	Catalina Research Institute	Chino	California	United States	91710
4	Synergy Escondido	Escondido	California	United States	92025
5	Collaborative Neuroscience Network Inc.,12772 Valley View Street	Garden Grove	California	United States	92645
6	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
7	University of California at Irvine Medical Center	Orange	California	United States	92868
8	CNRI - Los Angeles LLC,8309 Telegraph Road	Pico Rivera	California	United States	90660
9	CNRI - San Diego, LLC	San Diego	California	United States	92102
10	Stanford University School of Medicine	Stanford	California	United States	94305
11	University of Colorado	Aurora	Colorado	United States	80045
12	Depression and Anxiety Disorders Research Institue	Tampa	Florida	United States	33613
13	American Medical Research Inc.,1200 Harger Road Suite 415	Oak Brook	Illinois	United States	60523
14	American Medical Research, Inc., 1200 Harger Road Suite 415	Oak Brook	Illinois	United States	60523
15	J. Gary Booker, MD	Shreveport	Louisiana	United States	71104
16	Sheppard Pratt Health System,6501 North Charles Street	Baltimore	Maryland	United States	21285
17	Capital Clinical Research,5515 Security Lane, Suite 525	Rockville	Maryland	United States	20852
18	Midwest Research Group	St. Charles	Missouri	United States	63301
19	Albuquerque Neuroscience Inc.,101 Hospital Loop, Suite 209	Albuquerque	New Mexico	United States	87109
20	Lake Charles Clinical Trials LLC,700 Spring Forest Road	Raleigh	North Carolina	United States	27609
21	Richard H. Weisler , M.D., PA.,& Associates, 700 Spring Forest Road, Suite 125	Raleigh	North Carolina	United States	27609
22	University of Cincinnati	Cincinnati	Ohio	United States	45219
23	Mood Disorders Program-UHCMC	Cleveland	Ohio	United States	44106
24	MetroHealth System	Cleveland	Ohio	United States	44122
25	Midwest Clinical research Center, One Elizabeth Place, Suite G-3	Dayton	Ohio	United States	45408
26	CRI Worldwide, LLC	Philadelphia	Pennsylvania	United States	19139
27	FutureSearch Clinical Trials, LLC., 4200 Marathon Blvd., Suite 200	Austin	Texas	United States	78756
28	Psychiatricka ambulance	Brno - mesto		Czech Republic	602 00
29	BIALBI s.r.o. Psychiatricke oddeleni	Litomerice		Czech Republic	412 01
30	Clintrial, s.r.o.	Praha		Czech Republic	10 100 00
31	Medical Services Prague s.r.o.	Praha		Czech Republic	6 160 00
32	Psychiatricka ambulance Prosek	Praha		Czech Republic	9 190 00
33	Hopital Caremeau, Service de Psychiatrie A	Nimes Cedex		France	30 30029
34	Zans Ritter, Marcel	Orvault		France	44700
35	Jana Thomsen	Berlin BE		Germany	10245
36	SV Medical College	Tirupati	Andh Prad	India	517507
37	Vijayawada Institute of Mental Health and Neurosciences, Psychiatry	Vijaywada	Andh Prad	India	520002
38	Samvedna Hospitals	Ahmedabad	Gujarat	India	380006
39	Sheth Vadilal Sarabhai General Hospital	Ahmedabad	Gujarat	India	380006
40	Mental Illness Treatment Rehabilitation Foundation (MITR)	Ahmedabad	Gujarat	India	380013
41	Shree Hatkesh Health Foundation	Junagadh	Gujarat	India	362001
42	Spandana Nursing Home	Bangalore	Karna	India	560010
43	Sujata Birla Hospital & Research Centre	Nashik	Mahara	India	422101
44	R.K. Yadav Memorial Mental Health & De-Addiction Hospital	Jaipur	Rajasthan	India	302021
45	Manobal Med. Research Centre	Lucknow	Uttar Prad	India	226006
46	Cosmos Hospitals-Delhi Psychiatry Center-Dept. of Psychiatry	Delhi		India	110092
47	ZOZ Poradnia Zdrowia Psychicznego	Chelmno		Poland	86-200
48	Praktyka Lekarska Sensorium S.M.O.	Skorzewo		Poland	60-185
49	Wojewodzki Szpital Brodnowski SP ZOZ	Warszawa		Poland	03-242
50	Spitalul Clinic de Urgenta Militar Central "Prof. Dr. Carol" Psihiatrie	Bucuresti		Romania	010825
51	Spitalul Clinic de Psihaiatrie Prof. Dr. Alexandru Obregia	Bucuresti		Romania	041914
52	Spitalul Clinic Judetean de Urgenta Cluj	Cluj-Napoca		Romania	400012
53	Spitalul Clinic de Neuropsihiatrie Craiova	Craiova		Romania	200620
54	Spitalul Clinic de Neurologie si Psihiatrie Oradea	Oradea		Romania	410154
55	Spitalul Judetean de Urgenta Pitesti Sectia de Psihiatric	Pitesti		Romania	110069
56	Russian State Medical University	Moscow		Russian Federation	117997
57	Moscow Medical Academy named I.M. Sechenov	Moscow		Russian Federation	119435
58	City Psychiatric Hospital #2 of St. Nikolay Chudotvorets	St. Petersburg		Russian Federation	190121
59	Bekhterev Scientific Research Psychoneurological Institute	St. Petersburg		Russian Federation	193019
60	Psychoneurology Dispensary #4	St. Petersburg		Russian Federation	197110
61	LLC International Medical Centre "SOGAZ"	St. Petersburg		Russian Federation	198035
62	Cape Trial Centre	Cape Town, W. Cape		South Africa	7530
63	Paarl Medical Centre	Paarl, W. Cape		South Africa	7646
64	Clinika	Port Elizabeth, E. Cape		South Africa	6000
65	Dey Clinic	Pretoria, Gauteng		South Africa	0181
66	Vereeniging Medi-Clinic	Vereeniging, Free State		South Africa	1941
67	Reg. Clinic Psych. Hosp., Dept 11, DNMU n.a.M. Gorkiy	Donetsk		Ukraine	83008
68	Odesa Regional Psychoneurological Dispensary	Odesa		Ukraine	65014
69	Reg. Ci.Ps.H.n.a.O.F.Maltsev, Fem.Ac.Gen.Ps. D.5B,HESIU UM	Poltava		Ukraine	36006
70	CRI"Cl. Psych.Hosp.#1, Fem Psych.Dept.#2, Male Psych.Dept.#1	Simferopol		Ukraine	95006
71	Reg. Psych. Hosp. n.a. O.Yuschenko, Dept. #21, VNMUn.a.M. Pirog	Vinnitsia		Ukraine	21005

Sponsors and Collaborators

• Sunovion

Investigators

• Study Director: Medical Director, MD, Sunovion

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT00868452
• Other Study ID Numbers: D1050235; EUDRACT No. 2008-007482-23
• First Posted: Mar 25, 2009
• Last Update Posted: Apr 17, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Sunovion: Bipolar I; Latuda; Lurasidone
• Additional relevant MeSH terms: Depression; Depressive Disorder; Bipolar Disorder; Valproic Acid; Lithium Carbonate; Lurasidone Hydrochloride

Study Results

Participant Flow

Recruitment Details	5/11/2009 - 1/9/2012

Arm/Group Title	Lurasidone	Placebo
Arm/Group Description	lurasidone + (lithium or divalproex) : lurasidone 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7.	Placebo + (lithium or divalproex) : 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7
Period Title: Overall Study
STARTED	183	165
COMPLETED	143	136
NOT COMPLETED	40	29

Baseline Characteristics

Arm/Group Title	Lurasidone	Placebo	Total
Arm/Group Description	lurasidone + (lithium or divalproex) : lurasidone 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7.	Placebo + (lithium or divalproex) : 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7	Total of all reporting groups
Overall Participants	179	161	340
Age (Count of Participants)
<=18 years	0 0%	1 0.6%	1 0.3%
Between 18 and 65 years	178 99.4%	155 96.3%	333 97.9%
>=65 years	1 0.6%	5 3.1%	6 1.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.0 (11.53)	42.6 (11.75)	41.7 (11.65)
Sex: Female, Male (Count of Participants)
Female	86 48%	76 47.2%	162 47.6%
Male	93 52%	85 52.8%	178 52.4%
Region of Enrollment (participants) [Number]
France	8 4.5%	8 5%	16 4.7%
United States	58 32.4%	52 32.3%	110 32.4%
Czech Republic	27 15.1%	21 13%	48 14.1%
Poland	9 5%	6 3.7%	15 4.4%
Ukraine	11 6.1%	12 7.5%	23 6.8%
Romania	2 1.1%	3 1.9%	5 1.5%
South Africa	10 5.6%	8 5%	18 5.3%
Russian Federation	9 5%	10 6.2%	19 5.6%
Germany	2 1.1%	4 2.5%	6 1.8%
India	43 24%	37 23%	80 23.5%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6)
Description	MADRS total score ranges from a minimum of 0 to a maximum of 60. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set (intent-to-treat population)

Arm/Group Title	Lurasidone	Placebo
Arm/Group Description	lurasidone + (lithium or divalproex) : lurasidone 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7.	Placebo + (lithium or divalproex) : 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7
Measure Participants	179	161
Least Squares Mean (Standard Error) [units on a scale]	-17.1 (0.87)	-13.5 (0.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.6
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.25
	Estimation Comments

2. Secondary Outcome

Title	Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression)
Description	CGI-EP-S depression score ranges from a minimum of 0 to a maximum of 7. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening.
Time Frame	Baseline Week 6

Outcome Measure Data

Analysis Population Description

Full analyis set (intent-to-treat population)

Arm/Group Title	Lurasidone	Placebo
Arm/Group Description	lurasidone + (lithium or divalproex) : lurasidone 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7.	Placebo + (lithium or divalproex) : 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7
Measure Participants	179	161
Least Squares Mean (Standard Error) [units on a scale]	-1.96 (0.104)	-1.51 (0.109)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.44
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.150
	Estimation Comments

3. Secondary Outcome

Title	Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score
Description	STS total score ranges from a minimum of 0 to a maximum of 30. Lower values represent a better score, higher values represent a worse score. Similarly, greater negative change from baseline represents improvement, and positive changes from baseline represent worsening.
Time Frame	Baselin Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set (intent-to-treat population)

Arm/Group Title	Lurasidone	Placebo
Arm/Group Description	lurasidone + (lithium or divalproex) : lurasidone 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7	Placebo + (lithium or divalproex) : 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7
Measure Participants	179	161
Least Squares Mean (Standard Deviation) [units on a scale]	-9.5 (0.78)	-7.0 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.6
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.01
	Estimation Comments

Adverse Events

Time Frame	Adverse event reporting begins at time of informed consent signature and continues until patient discontinuatiion - 6 Weeks
Adverse Event Reporting Description	Number of participants at risk is the Safety Analysis Set (all randomized subjects exposed to at least one dose of study medicaton).
Arm/Group Title	Lurasidone		Placebo
Arm/Group Description	lurasidone + (lithium or divalproex) : lurasidone 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7.		Placebo + (lithium or divalproex) : 20 mg/day for Days 1-2-3, 40 mg/day for Days 4-5-6, and 60 mg/day on Day 7
All Cause Mortality
	Lurasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lurasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/183 (1.1%)		2/163 (1.2%)
Injury, poisoning and procedural complications
Femur Fracture	0/183 (0%)	0	1/163 (0.6%)	1
Psychiatric disorders
Suicidal Ideation	1/183 (0.5%)	1	1/163 (0.6%)	1
Depression	1/183 (0.5%)	1	0/163 (0%)	0
Other (Not Including Serious) Adverse Events
	Lurasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/183 (39.9%)		51/163 (31.3%)
Gastrointestinal disorders
Nausea	32/183 (17.5%)	44	18/163 (11%)	24
Diarrhea	8/183 (4.4%)	10	11/163 (6.7%)	12
Nervous system disorders
Headache	19/183 (10.4%)	30	20/163 (12.3%)	29
Somnolence	17/183 (9.3%)	17	7/163 (4.3%)	9
Tremor	15/183 (8.2%)	17	7/163 (4.3%)	8
Akathisia	14/183 (7.7%)	18	7/163 (4.3%)	10
Psychiatric disorders
Insomnia	13/183 (7.1%)	21	9/163 (5.5%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

In addition to the <60-180 day restriction above, since this is a multicenter study, 1st publication of study results shall be made with other participating study sites as a multicenter publication; provided, if a multicenter publication is not forthcoming within 24 months following completion of study at all sites, the PI shall be free to publish.