PEARL 3: Lurasidone HCL - A 6-week Phase 3 Study of Patients With Acute Schizophrenia.

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00790192
• Collaborator: (none)
• Enrollment: 488
• Locations: 65
• Arms: 4
• Duration (Months): 21
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Lurasidone HCl is a compound being developed for the treatment of schizophrenia. This clinical study is designed to test the hypothesis that lurasidone is effective, tolerable, and safe as compared with quetiapine XR short term among acutely psychotic patients with chronic schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Lurasidone; Drug: Lurasidone; Drug: Quetiapine XR; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 488 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Clinical Trial to Study the Efficacy and Safety of Two Doses of Lurasidone in Acutely Psychotic Subjects With Schizophrenia (PEARL 3)
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lurasidone 80mg	Drug: Lurasidone; Lurasidone 80 mg tablets
Experimental: Lurasidone 160mg	Drug: Lurasidone; Lurasidone 4 40 mg tablets
Active Comparator: Quetiapine XR	Drug: Quetiapine XR; Quetiapine XR 600mg
Placebo Comparator: Placebo	Drug: Placebo; Matching Placebo to Lurasidone or Quetiapine

Outcome Measures

Primary Outcome Measures

1. Primary Efficacy Endpoint: Mean Change in Total PANSS Score From Baseline to the End of the Double Blind Phase [Week 6]

   The PANSS (Positive and Negative Syndrome Scale) is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.

Secondary Outcome Measures

1. Secondary Outcome: CGI-S From Baseline to the End of the Double-blind Treatment [6-Weeks]

   Clinical Global Impression of Severity is a clinician-rated assessment of the subject's current illness state on a 7 point scale, where a higher score is associated with greater illness severity. The scale has a single item measured on a 7 point scale from 1 ('normal', not ill) to 7 (extremely ill).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Provide written informed consent and aged between 18 and 75 years of age.

• Meets DSM-IV™ criteria for a primary diagnosis of schizophrenia.

• Not pregnant, if of reproductive potential agrees to remain abstinent or use adequate and reliable contraception for duration of study.

• Able and agrees to remain off prior antipsychotic medication for the duration of study.

• Good physical health on the basis of medical history, physical examination, and laboratory screening.

• Willing and able to comply with the protocol, including the inpatient requirements and outpatient visits.

Exclusion Criteria:

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

• Any chronic organic disease of the CNS (other than schizophrenia).

• Used investigational compound within 30 days.

• Clinically significant or history of alcohol abuse/alcoholism or drug abuse/dependence within the last 6 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	K&S Professional Research Services, LLC	Little Rock	Arkansas	United States	72201
2	Woodland International Research Group	Little Rock	Arkansas	United States	72211
3	Clinical Pharmacological Studies, Inc.	Cerritos	California	United States	90703
4	Comprehensive Neuroscience, Inc	Cerritos	California	United States	90703
5	Clinical Innovations, Inc.	Costa Mesa	California	United States	92647
6	Synergy Escondido	Escondido	California	United States	92025
7	Collaborative Neuroscience Network	Garden Grove	California	United States	92645
8	Apostle Clinical Trials, Inc.	Long Beach	California	United States	90813
9	California Clinical Trials	Paramount	California	United States	90723
10	Pasadena Research Institute	Pasadena	California	United States	91107
11	CNRI-Los Angeles. LLC	Pico Rivera	California	United States	90660
12	Clinical Innovations, Inc.	Riverside	California	United States	92647
13	CNRI-San Diego	San Diego	California	United States	92126
14	UCSD Medical Center	Sandeigo	California	United States	92103
15	Segal Institute for Clinical Research	Highlands Ranch	Colorado	United States	80103
16	Comprehensive Neuroscience, Inc.	Washington	District of Columbia	United States	20016
17	Florida Clinical Research Center	Bradenton	Florida	United States	34208
18	Florida Clinical Research Center, LLC	Fruitland Park	Florida	United States	34731
19	Lake Charles Clinical Trials	Lake Charles	Louisiana	United States	70601
20	Booker, J. Gary, MD. APMC	Shreveport	Louisiana	United States	71104
21	Precise Clinical Research	Flowood	Mississippi	United States	39232
22	St. Charles Psychiatric Associates	St Charles	Missouri	United States	63301
23	St. Louis Research, Inc.	St. Louis	Missouri	United States	63118
24	CRI Worldwide	Willingboro	New Jersey	United States	08046
25	Comprehensive Neuroscience, Inc	Holliswood	New York	United States	11423
26	Segal Institute for Clinical Research	Winston-Salem	North Carolina	United States	27104
27	Community Clinical Research	Austin	Texas	United States	78729
28	Future Search Trials of Neurology	Austin	Texas	United States	78756
29	Pillar Clinical Research	Dallas	Texas	United States	75243
30	Vijayawada Institute of Mental Health and Neurosciences	Vijayawada	Andhra Pradesh	India	520002
31	S.V. Medical College	Tirupati	Andra Pradesh	India	517507
32	Seth K M School of P G Medicine & Research	Ahmedabad	Gujarat	India	380006
33	SBKS Medical Institute and Research Centre	Vadodara	Gujarat	India	391760
34	Justice K.S. Hegde Charitable Hospital	Mangalore	Karnataka	India	574160
35	JSS Medical College and Hospital	Mysore	Karnataka	India	570004
36	Shanti Nursing Home	Aurangabad	Maharastra	India	431005
37	Deenanath Mangeshkar Hospital and Research Centre	Pune	Maharastra	India	411004
38	Mahatma Gandhi Institute of Medical Sciences	Sewagram	Maharastra	India	442102
39	Madras Medical College & Government General Hospital	Chennai	TamilNadu	India	600003
40	Spitalul Clinic Judetean de Urgenta Arad	Str. Octavian Goga nr. 17	Arad	Romania	310022
41	Spitalul de Psihiatrie Titan "Dr. Constantin Gorgos"	Bdul Nicolae Grigorescu nr. 41	Bucuresti	Romania	030440
42	Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia	Sos. Berceni nr. 10-12	Bucuresti	Romania	041914
43	Spitalul Judetean Arges	Str. Negru Voda nr. 53	Pitesti	Romania	110069
44	Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia	Bucuresti		Romania
45	Spitalul Clinic de Neurologie si Psihiatrie Oradea	Oradea		Romania
46	SEI of H.P. Educat. Northern SMU	Arkhangelsk		Russian Federation	163060
47	St. Petersburg SHI Psychiatrical Hosptial #1 n.a. Kaschenko	Gatchina		Russian Federation	188357
48	Moscow Scientific Research Institute of Psychiatry	Moscow		Russian Federation	107076
49	Institution of RAMS Mental Health Research Center of RAMS	Moscow		Russian Federation	115522
50	City Clinical Psichiatric Hospital #1	Nizhniy Novgorod		Russian Federation	603 155
51	SHI Samara Psychiatric Hospital	Samara		Russian Federation	443016
52	City Psychiatric Hospital #2 of St. Nikolay Chudotvorets	St. Petersburg		Russian Federation
53	City Psychiatric Hospital #3 of Skvortsov-Stepanov	St. Petersburg		Russian Federation
54	City Psychiatric Hospital #4	St. Petersburg		Russian Federation
55	SHI City Psychoneurological Dispensary #7	St. Petersburg		Russian Federation
56	St. Petersburg GUZ City Psychiatric Hospital #6	St. Petersburg		Russian Federation
57	Kherson Regional Psychiatric Hospital	Kherson,vil.	Stepanovka	Ukraine	73488
58	RCH n.a.I.I.Mechnikov, Reg.Cent. of Psychosom. Pathology	Dnipropetrovsk		Ukraine	49005
59	Chair of Psychiatry and Medical Psychology	Donetsk		Ukraine	83008
60	Centre of Novel Treatment and Rehabilitation of Psychotic disorders	Kyiv		Ukraine
61	Kyiv City Psychoneurological Hospital	Kyviv		Ukraine
62	Lviv Reg.St.Cl.Psych.Hosp	Lviv		Ukraine
63	Reg. Psychiatric Hospital	Odessa		Ukraine
64	Poltava Regional Clinical Psychiatric Hospital,	Poltava		Ukraine
65	Crimean republican Clinical Psychiatric Hospital	Simferopol		Ukraine

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: NCT00790192
• Other Study ID Numbers: D1050233
• First Posted: Nov 13, 2008
• Last Update Posted: Mar 17, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Sunovion: Schizophrenia; SM-13496; Latuda; Lurasidone
• Additional relevant MeSH terms: Schizophrenia; Quetiapine Fumarate; Lurasidone Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Lurasidone 80 mg	Lurasidone 160 mg	Quetiapine XR 600mg	Placebo
Arm/Group Description	Lurasidone 80 mg tablets taken orally once a day	Lurasidone 160 mg (4 tablets) taken orally once a day	Quetiapine XR 600 mg (4 tablets) orally taken once a day	Matching placebo to either lurasidone or quetiapine XR. The total for this group is 73 and the adverse events only add up to 69 because the total is based on all treatment emergent adverse events not limited to >= 5%.
Period Title: Overall Study
STARTED	125	121	120	122
COMPLETED	89	93	97	74
NOT COMPLETED	36	28	23	48

Baseline Characteristics

Arm/Group Title	Lurasidone 80 mg	Lurasidone 160 mg	Quetiapine XR 600mg	Placebo	Total
Arm/Group Description	Lurasidone 80 mg tablets taken orally once a day	Lurasidone 160 mg (4 tablets) taken orally once a day	Quetiapine XR 600 mg (4 tablets) orally taken once a day	Matching placebo to either lurasidone or quetiapine XR. The total for this group is 73 and the adverse events only add up to 69 because the total is based on all treatment emergent adverse events not limited to >= 5%.	Total of all reporting groups
Overall Participants	125	121	120	122	488
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.2 (10.9)	37.9 (11.3)	37.4 (10.4)	37.4 (10.8)	37.2 (10.8)
Gender (participants) [Number]
Female	29 23.2%	39 32.2%	42 35%	44 36.1%	154 31.6%
Male	96 76.8%	82 67.8%	77 64.2%	77 63.1%	332 68%
Region of Enrollment (participants) [Number]
United States	40 32%	37 30.6%	35 29.2%	39 32%	151 30.9%
Ukraine	19 15.2%	20 16.5%	19 15.8%	17 13.9%	75 15.4%
Romania	13 10.4%	11 9.1%	13 10.8%	12 9.8%	49 10%
Russian Federation	22 17.6%	22 18.2%	21 17.5%	22 18%	87 17.8%
India	24 19.2%	25 20.7%	25 20.8%	24 19.7%	98 20.1%
Colombia	7 5.6%	6 5%	6 5%	7 5.7%	26 5.3%

Outcome Measures

1. Primary Outcome

Title	Primary Efficacy Endpoint: Mean Change in Total PANSS Score From Baseline to the End of the Double Blind Phase
Description	The PANSS (Positive and Negative Syndrome Scale) is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The primary population for the efficacy analysis was the Intent-to-Treat (ITT) population. All subjects who were randomized, received at least one dose of study medication, and have a Baseline efficacy measurement and at least one post-Baseline efficacy measurement, were in the efficacy analysis in the treatment group to which they were randomized.

Arm/Group Title	Lurasidone 80 mg	Lurasidone 160 mg	Quetiapine XR 600mg	Placebo
Arm/Group Description	Lurasidone 80 mg tablets taken orally once a day	Lurasidone 160 mg (4 tablets) taken orally once a day	Quetiapine XR 600 mg (4 tablets) orally taken once a day	Matching placebo to either lurasidone or quetiapine XR. The total for this group is 73 and the adverse events only add up to 69 because the total is based on all treatment emergent adverse events not limited to >= 5%.
Measure Participants	125	121	116	120
Least Squares Mean (95% Confidence Interval) [scores on a scale]	-22.2	-26.5	-27.8	-10.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 80 mg, Lurasidone 160 mg, Quetiapine XR 600mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Secondary Outcome: CGI-S From Baseline to the End of the Double-blind Treatment
Description	Clinical Global Impression of Severity is a clinician-rated assessment of the subject's current illness state on a 7 point scale, where a higher score is associated with greater illness severity. The scale has a single item measured on a 7 point scale from 1 ('normal', not ill) to 7 (extremely ill).
Time Frame	6-Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lurasidone 80 mg	Lurasidone 160 mg	Quetiapine XR 600mg	Placebo
Arm/Group Description	Lurasidone 80 mg tablets taken orally once a day	Lurasidone 160 mg (4 tablets) taken orally once a day	Quetiapine XR 600 mg (4 tablets) orally taken once a day	Matching placebo to either lurasidone or quetiapine XR. The total for this group is 73 and the adverse events only add up to 69 because the total is based on all treatment emergent adverse events not limited to >= 5%.
Measure Participants	125	121	116	120
Least Squares Mean (95% Confidence Interval) [scores on a scale]	-1.5	-1.7	-1.7	-0.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 80 mg, Lurasidone 160 mg, Quetiapine XR 600mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	14 days post study therapy
Arm/Group Title	Lurasidone 80 mg		Lurasidone 160 mg		Quetiapine XR 600mg		Placebo
Arm/Group Description	Lurasidone 80 mg tablets taken orally once a day		Lurasidone 160 mg (4 tablets) taken orally once a day		Quetiapine XR 600 mg (4 tablets) orally taken once a day		Matching placebo to either lurasidone or quetiapine XR. The total for this group is 73 and the adverse events only add up to 69 because the total is based on all treatment emergent adverse events not limited to >= 5%.
All Cause Mortality
	Lurasidone 80 mg		Lurasidone 160 mg		Quetiapine XR 600mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lurasidone 80 mg		Lurasidone 160 mg		Quetiapine XR 600mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/125 (0.8%)		4/121 (3.3%)		1/119 (0.8%)		4/121 (3.3%)
Cardiac disorders
Left Ventricular Dysfunction	1/125 (0.8%)	1	4/121 (3.3%)	4	1/119 (0.8%)	1	4/121 (3.3%)	4
Gastrointestinal disorders
Abdominal Hernia Obstructive	0/125 (0%)	0	1/121 (0.8%)	1	0/119 (0%)	0	0/121 (0%)	0
General disorders
Non-cardiac Chest Pain	0/125 (0%)	0	1/121 (0.8%)	1	0/119 (0%)	0	0/121 (0%)	0
Infections and infestations
Hepatitis Viral	0/125 (0%)	0	0/121 (0%)	0	1/119 (0.8%)	119	0/121 (0%)	0
Injury, poisoning and procedural complications
Hand Fracture	0/125 (0%)	0	1/121 (0.8%)	1	0/119 (0%)	0	0/121 (0%)	0
Psychiatric disorders
Agression	0/125 (0%)	0	0/121 (0%)	0	0/119 (0%)	0	1/121 (0.8%)	1
Pyschotic Disorder	0/125 (0%)	0	0/121 (0%)	0	1/119 (0.8%)	1	2/121 (1.7%)	2
Schizophrenia	0/125 (0%)	0	1/121 (0.8%)	1	0/119 (0%)	0	0/121 (0%)	0
Suicidal Behavior	0/125 (0%)	0	0/121 (0%)	0	0/119 (0%)	0	1/121 (0.8%)	1
Suicidal Ideation	0/125 (0%)	0	0/121 (0%)	0	0/119 (0%)	0	2/121 (1.7%)	2
Social circumstances
Physical Assault	1/125 (0.8%)	1	0/121 (0%)	0	0/119 (0%)	0	0/121 (0%)	0
Vascular disorders
Labile Hypertension	0/125 (0%)	0	1/121 (0.8%)	1	0/119 (0%)	0	0/121 (0%)	0
Other (Not Including Serious) Adverse Events
	Lurasidone 80 mg		Lurasidone 160 mg		Quetiapine XR 600mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/125 (56.8%)		76/121 (62.8%)		70/119 (58.8%)		69/121 (57%)
Gastrointestinal disorders
Constipation	3/125 (2.4%)	3	1/121 (0.8%)	1	8/119 (6.7%)	8	3/121 (2.5%)	3
Dry Mouth	2/125 (1.6%)	2	2/121 (1.7%)	2	9/119 (7.6%)	9	1/121 (0.8%)	1
Dyspepsia	3/125 (2.4%)	3	7/121 (5.8%)	7	3/119 (2.5%)	3	4/121 (3.3%)	4
Nausea	10/125 (8%)	10	8/121 (6.6%)	8	4/119 (3.4%)	4	4/121 (3.3%)	4
Vomiting	8/125 (6.4%)	8	9/121 (7.4%)	9	6/119 (5%)	6	6/121 (5%)	6
Infections and infestations
Upper Respiratory Tract Infection	2/125 (1.6%)	2	1/121 (0.8%)	1	6/119 (5%)	6	1/121 (0.8%)	1
Investigations
Weight Increase	1/125 (0.8%)	1	2/121 (1.7%)	2	8/119 (6.7%)	8	1/121 (0.8%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/125 (1.6%)	2	1/121 (0.8%)	1	7/119 (5.9%)	7	1/121 (0.8%)	1
Nervous system disorders
Akathisia	10/125 (8%)	10	9/121 (7.4%)	9	2/119 (1.7%)	2	1/121 (0.8%)	1
Dizziness	6/125 (4.8%)	6	7/121 (5.8%)	7	16/119 (13.4%)	16	2/121 (1.7%)	2
Headache	12/125 (9.6%)	12	12/121 (9.9%)	12	13/119 (10.9%)	13	13/121 (10.7%)	13
Parkinsonism	7/125 (5.6%)	7	8/121 (6.6%)	8	4/119 (3.4%)	4	0/121 (0%)	0
Somnolence	5/125 (4%)	5	8/121 (6.6%)	8	16/119 (13.4%)	16	1/121 (0.8%)	1
Psychiatric disorders
Agitation	4/125 (3.2%)	4	6/121 (5%)	6	3/119 (2.5%)	3	10/121 (8.3%)	10
Anxiety	9/125 (7.2%)	9	4/121 (3.3%)	4	1/119 (0.8%)	1	10/121 (8.3%)	10
Insomnia	14/125 (11.2%)	14	8/121 (6.6%)	8	5/119 (4.2%)	5	11/121 (9.1%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.