A Twelve Week, Open Label Extension Study in Patients With Schizophrenia

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01566162
• Collaborator: (none)
• Enrollment: 191
• Locations: 63
• Arm: 1
• Duration (Months): 19
• Patients Per Site: 3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a 12-week, multi-center, open-label extension study designed to evaluate the longer-term safety, tolerability and effectiveness of lurasidone for the treatment of subjects with schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Lurasidone	Phase 3

Detailed Description

This is a 12-week, multi-center, open-label extension study designed to evaluate the longer-term safety, tolerability and effectiveness of lurasidone for the treatment of subjects with schizophrenia who have participated in Study D1050238, a double-blind, placebo-controlled, randomized withdrawal study of lurasidone for the maintenance treatment of subjects with schizophrenia. Subjects who have completed the 28-week double-blind phase or who have experienced a protocol-defined relapse event during the double-blind phase of study D1050238 will have the option to participate in this study. In addition, if/when the study is discontinued by the sponsor, all subjects participating in the open-label phase and the double-blind phase of study D1050238 will have the option to participate in this extension study

Study Design

• Study Type: Interventional
• Actual Enrollment: 191 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Twelve Week, Multicenter, Open Label Extension Study in Subjects With Schizophrenia
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lurasidone Lurasidone 40 - 80mg flexible dose	Drug: Lurasidone; Lurasidone 40-80 mg taken orally taken once daily

Outcome Measures

Primary Outcome Measures

1. Safety - Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious AEs (SAEs) [12 weeks]

   Number of subjects with treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation, and serious AEs (SAEs)

2. Efficacy - Change in Positive and Negative Syndrome Scale (PANSS) Total Score [Baseline to week 12 LOCF endpoint]

   The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS total score is the sum of all 30 items and ranges from 30 through 210. A higher score is associated with greater illness severity.

3. Efficacy - Change From Baseline in Clinical Global Impression-Severity of Illness (CGI-S) Score. [Baseline to week 12 LOCF endpoint]

   The CGI-S score is a single value, clinician-rated assessment of illness severity and ranges from 1= 'Normal, not at all ill' to 7= 'Among the most extremely ill patients'. A higher score is associated with greater illness severity.

Secondary Outcome Measures

1. Change From Baseline in Montgomery -Asberg Depression Rating Scale Total Score [Baseline to week 12 LOCF endpoint]

   The MADRS consists of 10 items, each rated on a Likert scale, from 0="Normal" to 6="Most Severe". The MADRS total score is calculated as the sum of the 10 items. The MADRS total score ranges from 0 to 60. Higher scores are associated with greater severity.

2. Short Form-12 Health Survey (SF-12) [Baseline to week 12 LOCF endpoint]

   The SF-12v2 is a self-administered, multipurpose short-form (SF) generic measure of health status. It was developed to be a shorter, yet valid, alternative to the SF-36 for use in large surveys of general and specific populations as well as in large longitudinal studies of health outcomes. The 12 items in the SF-12v2 are a subset of those in the SF-36; SF-12v2 includes one or two items from each of the eight health concepts with higher scores indicative of higher functioning and better health. The Physical Component Score is a composite of the Physical Functioning, Role Functioning, Bodily Pain and General Health scales. Physical Composite Scores (PCS) is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

3. Modified Specific Levels of Functioning (SLOF) Total Score. [12 weeks]

   The modified SLOF scale is designed to measure directly observable behavioral functioning and daily living skills of patients with chronic mental illness. The modified SLOF consists of 24 items, each item is rated on a 5-point scale and mapped to 0 to 4. The total score will be the sum of all 24 items and ranges from 0 to 96. A higher score indicates worse condition.

4. Brief Adherence Rating Scale (BARS) [12 weeks]

   The Brief Adherence Rating Scale (BARS) is a clinician-administered adherence assessment instrument that consists of four items including three questions and a visual analog rating scale (VAS) to assess the percentage (0 100%) of doses taken by the subject in the previous month.

5. Smoking Questionnaire [12 weeks]

   Smoking questionnaire - average number of cigarettes per day at week 12 (LOCF).

6. Intent to Attend Assessment [12 weeks]

   The ITA assessment will be administered by a research staff member. The response is recorded on a 10-point scale, with 0 = "Not at all" and 9 = "Extremely". The ITA allowed the site to capture data regarding dropout risk. The following question was completed at the baseline visit: "How likely is it that you will complete the study?"

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject has agreed to participate by providing written informed consent.

• Subject will be eligible to participate if one of the following criteria is met:

• Subject has completed the 28-week double-blind phase of study D1050238

• Subject has experienced a protocol-defined relapse event during the double- blind phase in study D1050238

• Subject is participating in the open-label or double-blind phase of study D1050238 if/when study D1050238 is terminated by the sponsor.

• Subject has completed all required assessments on the final study visit (Study Visit Number 42) in study D1050238.

• Subject is judged by the Investigator to be suitable for participation in a 12-week clinical trial involving open-label lurasidone treatment and is able to comply with the protocol in the opinion of the Investigator.

Exclusion Criteria:

• Subject is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property.

• Subject answers "yes" to "Suicidal Ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS at the extension baseline visit (Study Visit Number 42 in study D1050238). Subjects who answer "yes" to this question must be referred by the Investigator for appropriate follow-up evaluation and treatment.

• Subject tests positive for drugs of abuse or is suspected of current alcohol abuse at the extension baseline visit (Study Visit Number 42 in study D1050238). In the event a subject tests positive for cannabinoids, the Investigator will evaluate the subject's ability to abstain from cannabis during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	K and S Professional Research Services	Little Rock	Arkansas	United States	72201
2	Woodland International Research Inc.	Little Rock	Arkansas	United States	72211
3	Comprehensive Clinical Development Inc.	Cerritos	California	United States	90703
4	Diligent Clinical Trials	Downey	California	United States	90241
5	Synergy Clinical Research Center	Escondido	California	United States	92025
6	CNS Network	Garden Grove	California	United States	92845
7	AXIS Clinical Trials	Los Angeles	California	United States	90036
8	Synergy Clinical Research Center	National City	California	United States	91950
9	Excell Research, Inc.	Oceanside	California	United States	92056
10	CNRI-Los Angeles. LLC	Pico Rivera	California	United States	90660
11	California Neuropsychopharmacolgoy Clinical Research Insitute	San Diego	California	United States	92126
12	Neuropsychiatric Research Center of Orange County	Santa Ana	California	United States	92701
13	Collaborative Neuroscience Network	Torrance	California	United States	90502
14	Florida Clinical Research Center, LLC	Bradenton	Florida	United States	34208
15	Accurate Clinical Trials	Kissimmee	Florida	United States	34742
16	Galiz Research	Miami Springs	Florida	United States	33166
17	Medical Research Group of Central Florida	Orange City	Florida	United States	32763
18	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30308
19	Comprehensive NeuroScience Inc.	Atlanta	Georgia	United States	30328
20	Lake Charles Clinical Trials, LLC	Lake Charles	Louisiana	United States	70601
21	Lousiana Clinical Research, LLC	Shreveport	Louisiana	United States	71104
22	Center for Behavioral Health, LLC	Rockville	Maryland	United States	20850
23	Psychiatric Care and Research Center	O'Fallon	Missouri	United States	63368
24	Psych Care Consultants Research	Saint Louis	Missouri	United States	63128
25	Robert Lynn Horne, MD	Las Vegas	Nevada	United States	89102
26	CRI Worldwide LLC	Willingboro	New Jersey	United States	08046
27	Erie County Medical Center, Corp	Buffalo	New York	United States	14215
28	Neurobehavioral Research Inc.	Cedarhurst	New York	United States	11516
29	Comprehensive Clinical Development, Inc	Fresh Meadows	New York	United States	11366
30	Finger Lakes Clinical Research	Rochester	New York	United States	14618
31	Oklahoma Clinical Research	Oklahoma City	Oklahoma	United States	73116
32	CRI Worldwide LLC at Kirkbride	Philadelphia	Pennsylvania	United States	19139
33	Lincoln Research	Lincoln	Rhode Island	United States	02865
34	Community Clinical Research, Inc.	Austin	Texas	United States	78754
35	FutureSearch Clinical Trials LP	Austin	Texas	United States	78756
36	FutureSearch Clinical Trials, LP	Dallas	Texas	United States	75231
37	Pillar Clinical Research, LLC	Dallas	Texas	United States	75243
38	Department of Psychiatry, University of Utah Health Sciences Center	Salt Lake City	Utah	United States	84132
39	Centre Hospitalier Spécialisé (CHS) du Jura - Centre Médico Psychiatrique (CMP)	Dole		France	39100
40	Hôpital Chalucet, Centre hospitalier intercommunal de Toulon la Seyne sur mer (CHITS)	Toulon		France	83000
41	Dipartimento Salute Mentale ASL 1	Massa		Italy	54100
42	A.O.U. Santa Chiara, U.O di Psichiatria 1 building n.4	Pisa		Italy	56100
43	Regional Government Institution (RGI) 'Lipetsk Regional Psychoneurology Hospital'	Lipetsk		Russian Federation	398007
44	Limited Liability Company (LLC) 'Research Center For Treatment and rehabilitation 'Phoenix'	Rostov-on-Don		Russian Federation	344000
45	St. Petersburg State Healthcare Institution (SPbSHI) "City Psychiatric Hospital #6"	St. Peterburg		Russian Federation	191167
46	St. Petersburg State Budgetary Healthcare Institution 'City Psychoneurology Dispensary #7 (with In-Patient Department)', (SPb SBHI "CPNDD-7")	St. Petersburg		Russian Federation	190005
47	St. Petersburg State Budgetary Healthcare Institution 'City Psychoneurology Dispensary #7 (with In-Patient Department)', (SPb SBHI "CPNDD-7"), at Daycare Facility #1	St. Petersburg		Russian Federation	19005
48	St. Petersburg State Government Healthcare Institution "City Psychiatric Hospital #4" (St. Petersburg Insane Asylum Distributor)	St. Petersburg		Russian Federation	191119
49	Military Medical Academy, Clnic for Psychiatry	Belgrade		Serbia	11000
50	Institute of Mental Health	Dusica		Serbia	11000
51	Clinical Centre Kragujevac, Clinic for psychiatry	Kragujevac		Serbia	34000
52	Clinical Centre Nis, Clinic for mental health protection	Nis		Serbia	18000
53	Specialized hospital for psychiatric diseases "Sveti Vracevi"	Novi Knezevac		Serbia	23330
54	Clinical Centre Vojvodine, Clinic for Psychiatry	Novi Sad		Serbia	21000
55	Nemocnica s poliklinikou v Prievidzi so sidlom v Bojniciach, Psychiatricke oddelenie	Bojnice		Slovakia	972 01
56	Psychiatricka ambulancia Mentum s.r.o.	Bratislava		Slovakia	82007
57	Psychiatricka nemocnica Michalovce n.o.	Michalovce		Slovakia	071 01
58	PsychoLine s.r.o. Psychiatricka ambulancia	Rimavska Sobota		Slovakia	97901
59	Nemocnica s poliklinikou sv Barbory Roznava a.s. Psychiatricke oddelenie	Roznava		Slovakia	048 01
60	"Centrum zdravia R.B.K., spol. s.r.o.	Svidnik		Slovakia	089 01
61	Cape Trial Centre	Tygervalley	Western Cape	South Africa	7530
62	Research Unit, Department of Psychiatry Free State Psychiatric Complex	Bloemfontein		South Africa	9300
63	Denmar Hospital Consulting Rooms	Pretoria		South Africa	0081

Sponsors and Collaborators

• Sunovion

Investigators

• Study Director: Lurasidone Medical Director, MD, Sunovion

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT01566162
• Other Study ID Numbers: D1050307; 2011-004790-90
• First Posted: Mar 29, 2012
• Last Update Posted: Apr 9, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Sunovion: Lurasidone; Latuda; Schizophrenia
• Additional relevant MeSH terms: Schizophrenia; Lurasidone Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
Period Title: Overall Study
STARTED	191
COMPLETED	155
NOT COMPLETED	36

Baseline Characteristics

Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
Overall Participants	191
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	42.7 (12.30)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	190 99.5%
>=65 years	1 0.5%
Sex: Female, Male (Count of Participants)
Female	76 39.8%
Male	115 60.2%
Region of Enrollment (participants) [Number]
Serbia	22 11.5%
France	4 2.1%
United States	114 59.7%
Slovakia	15 7.9%
Russia	19 9.9%
South Africa	17 8.9%

Outcome Measures

1. Primary Outcome

Title	Safety - Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious AEs (SAEs)
Description	Number of subjects with treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation, and serious AEs (SAEs)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
Measure Participants	191
Subjects with TEAEs	72 37.7%
TEASs leading to discontinuation	7 3.7%
Subjects with TESAEs	13 6.8%

2. Primary Outcome

Title	Efficacy - Change in Positive and Negative Syndrome Scale (PANSS) Total Score
Description	The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS total score is the sum of all 30 items and ranges from 30 through 210. A higher score is associated with greater illness severity.
Time Frame	Baseline to week 12 LOCF endpoint

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
Measure Participants	191
Mean (Standard Deviation) [units on a scale]	-8.4 (15.06)

3. Primary Outcome

Title	Efficacy - Change From Baseline in Clinical Global Impression-Severity of Illness (CGI-S) Score.
Description	The CGI-S score is a single value, clinician-rated assessment of illness severity and ranges from 1= 'Normal, not at all ill' to 7= 'Among the most extremely ill patients'. A higher score is associated with greater illness severity.
Time Frame	Baseline to week 12 LOCF endpoint

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
Measure Participants	191
Mean (Standard Deviation) [units on a scale]	-0.48 (1.051)

4. Secondary Outcome

Title	Change From Baseline in Montgomery -Asberg Depression Rating Scale Total Score
Description	The MADRS consists of 10 items, each rated on a Likert scale, from 0="Normal" to 6="Most Severe". The MADRS total score is calculated as the sum of the 10 items. The MADRS total score ranges from 0 to 60. Higher scores are associated with greater severity.
Time Frame	Baseline to week 12 LOCF endpoint

Outcome Measure Data

Analysis Population Description

Only 182 subjects had post-baseline MADRS assessments.

Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
Measure Participants	182
Mean (Standard Deviation) [units on a scale]	-3.3 (7.83)

5. Secondary Outcome

Title	Short Form-12 Health Survey (SF-12)
Description	The SF-12v2 is a self-administered, multipurpose short-form (SF) generic measure of health status. It was developed to be a shorter, yet valid, alternative to the SF-36 for use in large surveys of general and specific populations as well as in large longitudinal studies of health outcomes. The 12 items in the SF-12v2 are a subset of those in the SF-36; SF-12v2 includes one or two items from each of the eight health concepts with higher scores indicative of higher functioning and better health. The Physical Component Score is a composite of the Physical Functioning, Role Functioning, Bodily Pain and General Health scales. Physical Composite Scores (PCS) is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time Frame	Baseline to week 12 LOCF endpoint

Outcome Measure Data

Analysis Population Description

Only 182 subjects had post-baseline SF-12.v2 assessments.

Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
Measure Participants	182
Mean (Standard Deviation) [units on a scale]	-0.45 (6.642)

6. Secondary Outcome

Title	Modified Specific Levels of Functioning (SLOF) Total Score.
Description	The modified SLOF scale is designed to measure directly observable behavioral functioning and daily living skills of patients with chronic mental illness. The modified SLOF consists of 24 items, each item is rated on a 5-point scale and mapped to 0 to 4. The total score will be the sum of all 24 items and ranges from 0 to 96. A higher score indicates worse condition.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Only 174 subjects had SLOF assessments at week 12 LOCF.

Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
Measure Participants	174
Mean (Standard Deviation) [units on a scale]	-1.8 (9.55)

7. Secondary Outcome

Title	Brief Adherence Rating Scale (BARS)
Description	The Brief Adherence Rating Scale (BARS) is a clinician-administered adherence assessment instrument that consists of four items including three questions and a visual analog rating scale (VAS) to assess the percentage (0 100%) of doses taken by the subject in the previous month.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
Measure Participants	182
Mean (Standard Deviation) [percentage of monthly doses taken]	99.0 (3.08)

8. Secondary Outcome

Title	Smoking Questionnaire
Description	Smoking questionnaire - average number of cigarettes per day at week 12 (LOCF).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Only 36 subjects who were smokers had the smoker questionnaire assessments.

Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
Measure Participants	36
Mean (Standard Deviation) [number of cigarettes smoked daily]	11.1 (9.95)

9. Secondary Outcome

Title	Intent to Attend Assessment
Description	The ITA assessment will be administered by a research staff member. The response is recorded on a 10-point scale, with 0 = "Not at all" and 9 = "Extremely". The ITA allowed the site to capture data regarding dropout risk. The following question was completed at the baseline visit: "How likely is it that you will complete the study?"
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Only 1825 subjects answered the questionnaire.

Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
Measure Participants	185
Mean (Standard Deviation) [units on a scale]	8.3 (1.14)

Adverse Events

Time Frame	12 Weeks
Arm/Group Title	Lurasidone
Arm/Group Description	Lurasidone 40 - 80mg flexible dose Lurasidone: Lurasidone 40-80 mg taken orally taken once daily
All Cause Mortality
	Lurasidone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lurasidone
	Affected / at Risk (%)	# Events
Total	13/191 (6.8%)
Cardiac disorders
Artrial flutter	1/191 (0.5%)	1
General disorders
Chest Pain	1/191 (0.5%)	1
Infections and infestations
Pneumonia	1/191 (0.5%)	1
Psychiatric disorders
Schizophrenia	6/191 (3.1%)	6
Psychotic Disorder	4/191 (2.1%)	5
Vascular disorders
Hypotension	1/191 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Lurasidone
	Affected / at Risk (%)	# Events
Total	34/191 (17.8%)
Gastrointestinal disorders
Diarrhoea	4/191 (2.1%)	4
Nausea	4/191 (2.1%)	5
Infections and infestations
Nasopharyngitis	5/191 (2.6%)	5
Nervous system disorders
Akathisia	10/191 (5.2%)	10
Headache	4/191 (2.1%)	5
Psychiatric disorders
Schizophrenia	8/191 (4.2%)	8
Anxiety	4/191 (2.1%)	9
Insomnia	4/191 (2.1%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS agreement between Principal Investigator and Sponsor that restricts PI's rights to discuss or publish trial results after trial is completed. 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 post completion of study at all sites, PI shall be free to publish.