A Clinical Trial of Lurasidone in Treatment of Schizophrenia

• Sponsor: Sumitomo Pharma (Suzhou) Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02002832
• Collaborator: (none)
• Enrollment: 388
• Locations: 15
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 25.9
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, double-dummy, parallel- controlled, adjustable dose, non-inferiority and multicentre study designed to evaluate the efficacy and safety of lurasidone on schizophrenia for 6 weeks treatment, and to compare with risperidone.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 388 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Double-dummy, Parallel-group and Multicenter Study to Investigate Lurasidone in Treatment of Schizophrenia Compared With Risperidone
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lurasidone group	Drug: Lurasidone tablets; Lurasidone tablets (40or80mg/day) and Risperidone tablets(Placebo); Other Names: LATUDA
Active Comparator: Risperidone group	Drug: Risperidone tablets; Risperidone tablets(2-6mg/day) and Lurasidone tablets(Placebo)

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Scores. [From baseline to Week 6(day 42).]

   Mean change in Positive and Negative Syndrome Scale total score from baseline to Week 6 at the end of treatment. PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. It have 30 evaluation items, which include 7 positive sub-scale, 7 negative sub-scale and 16 general psychopathology sub-scale on a score of 1 to 7. The total score is the sum of the 30 scale items. The minimum score is 30 and the maximum score is 210. Patient with PANSS total scores<70 is the normal,but the scores>120 is more serious.

Secondary Outcome Measures

1. Mean Clinical Global Impression Scale-Improvement (CGI-I) Score at Week 6. [From baseline to Week 6(day 42).]

   The Clinical Global Impression Scale-Improvement (CGI-I) Score is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to baseline state at the beginning of the intervention. Response is rated as one of the following, in which higher scores indicate less improvement or worsening: 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse, and 7=Very much worse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provide written informed consent and aged between 18 and 65 years of age.

• Meets DSM-IV-TR criteria for a primary diagnosis of schizophrenia, had a PANSS total score ≥ 70 and ≤ 120 at Screening and Baseline, and a score ≥ 4 on the CGI-S at Screening and Baseline.

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

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

• 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)

• Subjects are participating or participated in other clinical studies including marketed drugs or medical devices within 30 days before signing the informed consent form.

• 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	Capital Medical University Affiliated Beijing Anding Hospital	Beijing	Beijing	China	100088
2	Beijing Huilongguan Hospital	Beijing	Beijing	China	100096
3	Peking University Sixth Hospital	Beijing	Beijing	China	100191
4	Guangzhou Brain Hospital	Guangzhou	Guangdong	China	510370
5	HeBei Mental Health Center	Baoding	Hebei	China	071000
6	Henan Provincial Mental Hospital	Xinxiang	Henan	China	453002
7	The Second Xiangya Hospital of Central South University	Changsha	Hunan	China	410000
8	Hunan Province Brain Hospital	Changsha	Hunan	China	410007
9	Nanjing Brain Hospital	Nanjing	Jiangsu	China	210029
10	Wuxi Mental Health Center	Wuxi	Jiangsu	China	214000
11	Shanghai Mental Health Center	Shanghai	Shanghai	China	200030
12	Xi'an Mental Health Center	Xi'an	Shanxi	China	710061
13	West China Hospital, Sichuan University	Chengdu	Sichuan	China	610041
14	Tianjin Anding Hospital	Tianjin	Tianjin	China	300222
15	First Affiliated Hospital of Kunming Medical University	Kunming	Yunnan	China	650032

Sponsors and Collaborators

• Sumitomo Pharma (Suzhou) Co., Ltd.

Investigators

• Principal Investigator: Zhuoji CAI, MD, Capital Medical University Affiliated Beijing Anding Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sumitomo Pharma (Suzhou) Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02002832
• Other Study ID Numbers: D1070004
• First Posted: Dec 6, 2013
• Last Update Posted: Nov 15, 2019
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sumitomo Pharma (Suzhou) Co., Ltd.: schizophrenia; Lurasidone; LATUDA
• Additional relevant MeSH terms: Schizophrenia; Risperidone; Lurasidone Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Lurasidone Group	Risperidone Group
Arm/Group Description	Lurasidone 40 or 80 mg tablets taken orally once a day and Risperidone placebo tablets taken orally once a day	Risperidone 2-6mg tablets taken orally once a day and Lurasidone placebo tablets taken orally once a day.
Period Title: Overall Study
STARTED	194	194
COMPLETED	166	168
NOT COMPLETED	28	26

Baseline Characteristics

Arm/Group Title	Lurasidone Group	Risperidone Group	Total
Arm/Group Description	Lurasidone 40 or 80 mg tablets taken orally once a day and Risperidone placebo tablets taken orally once a day	Risperidone 2-6mg taken orally once a day and Lurasidone placebo tablets taken orally once a day.	Total of all reporting groups
Overall Participants	194	190	384
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	194 100%	190 100%	384 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.6 (11.12)	34.8 (10.71)	34.7 (10.91)
Sex: Female, Male (Count of Participants)
Female	96 49.5%	89 46.8%	185 48.2%
Male	98 50.5%	101 53.2%	199 51.8%
Region of Enrollment (participants) [Number]
China	194 100%	190 100%	384 100%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Scores.
Description	Mean change in Positive and Negative Syndrome Scale total score from baseline to Week 6 at the end of treatment. PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. It have 30 evaluation items, which include 7 positive sub-scale, 7 negative sub-scale and 16 general psychopathology sub-scale on a score of 1 to 7. The total score is the sum of the 30 scale items. The minimum score is 30 and the maximum score is 210. Patient with PANSS total scores<70 is the normal,but the scores>120 is more serious.
Time Frame	From baseline to Week 6(day 42).

Outcome Measure Data

Analysis Population Description

Intent-to-Treat 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 Group	Risperidone Group
Arm/Group Description	Lurasidone 40 or 80 mg tablets taken orally once a day and Risperidone placebo tablets taken orally once a day.	Risperidone 2-6mg tablets taken orally once a day and Lurasidone placebo tablets taken orally once a day.
Measure Participants	194	190
Least Squares Mean (95% Confidence Interval) [units on a scale]	-31.2	-34.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone Group, Risperidone Group
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	LS mean for the treatment difference(lurasidone-risperidone) at week 6 and its 95% confidence interval was presented based on the MMRM. Non-inferiority for lurasidone relative to risperidone was evaluated by comparing the upper bound of the 95% confidence interval to the non-inferiority margin of 7.0. Plots of estimates for change from baseline in PANSS total score based on MMRM over time (Week 1 to Week 6) with 95% confidence intervals was provided for each treatment group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.7
	Confidence Interval	(2-Sided) 95%; 1.0 to 6.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.37
	Estimation Comments

2. Secondary Outcome

Title	Mean Clinical Global Impression Scale-Improvement (CGI-I) Score at Week 6.
Description	The Clinical Global Impression Scale-Improvement (CGI-I) Score is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to baseline state at the beginning of the intervention. Response is rated as one of the following, in which higher scores indicate less improvement or worsening: 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse, and 7=Very much worse.
Time Frame	From baseline to Week 6(day 42).

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 Group	Risperidone Group
Arm/Group Description	Lurasidone 40 or 80 mg tablets taken orally once a day and Risperidone placebo tablets taken orally once a day	Risperidone 2-6mg tablets taken orally once a day and Lurasidone placebo tablets taken orally once a day.
Measure Participants	194	190
Least Squares Mean (95% Confidence Interval) [units on a scale]	2.0	1.9

Adverse Events

Time Frame	Date of first dose of study medication and up to 7 days after date of last dose of treatment in double-blind phase, an average of 7 weeks.
Adverse Event Reporting Description	Of the 388 randomized subjects, 385 subjects received at least 1 dose of study medication and were therefore included in the Safety population: 194 (100%) in the lurasidone group and 191 (98.5%) in the risperidone group.
Arm/Group Title	Lurasidone Group		Risperidone Group
Arm/Group Description	Lurasidone 40 or 80 mg tablets taken orally once a day and Risperidone placebo tablets taken orally once a day.		Risperidone 2-6mg tablets taken orally once a day and Lurasidone placebo tablets taken orally once a day.
All Cause Mortality
	Lurasidone Group		Risperidone Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/194 (0%)		0/191 (0%)
Serious Adverse Events
	Lurasidone Group		Risperidone Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/194 (0.5%)		0/191 (0%)
Injury, poisoning and procedural complications
Hand fracture	1/194 (0.5%)		0/191 (0%)
Other (Not Including Serious) Adverse Events
	Lurasidone Group		Risperidone Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/194 (69.1%)		160/191 (83.8%)
Blood and lymphatic system disorders
Anaemia	2/194 (1%)		4/191 (2.1%)
Cardiac disorders
Sinus bradycardia	7/194 (3.6%)		4/191 (2.1%)
Sinus tachycardia	2/194 (1%)		7/191 (3.7%)
Tachycardia	1/194 (0.5%)		5/191 (2.6%)
Endocrine disorders
Hyperprolactinaemia	1/194 (0.5%)		6/191 (3.1%)
Eye disorders
Vision blurred	1/194 (0.5%)		4/191 (2.1%)
Gastrointestinal disorders
Consitpation	25/194 (12.9%)		28/191 (14.7%)
Nausea	7/194 (3.6%)		4/191 (2.1%)
Vomiting	6/194 (3.1%)		3/191 (1.6%)
Diarrhoea	5/194 (2.6%)		5/191 (2.6%)
General disorders
Asthenia	3/194 (1.5%)		5/191 (2.6%)
Hepatobiliary disorders
Hepatic function abnormal	8/194 (4.1%)		6/191 (3.1%)
Infections and infestations
Nasopharyngitis	19/194 (9.8%)		28/191 (14.7%)
Upper respiratory tract infection	10/194 (5.2%)		16/191 (8.4%)
Investigations
Blood prolactin increased	6/194 (3.1%)		27/191 (14.1%)
Transaminases increased	2/194 (1%)		6/191 (3.1%)
Weight increased	1/194 (0.5%)		10/191 (5.2%)
Metabolism and nutrition disorders
Decreased appetite	1/194 (0.5%)		4/191 (2.1%)
Nervous system disorders
Extrapyramidal disorder	33/194 (17%)		73/191 (38.2%)
Akathisia	14/194 (7.2%)		26/191 (13.6%)
Dizziness	5/194 (2.6%)		8/191 (4.2%)
Poor quality sleep	3/194 (1.5%)		7/191 (3.7%)
Hypertonia	2/194 (1%)		6/191 (3.1%)
Psychiatric disorders
Insomnia	19/194 (9.8%)		19/191 (9.9%)
Anxiety	12/194 (6.2%)		12/191 (6.3%)
Initial insomnia	7/194 (3.6%)		6/191 (3.1%)
Agitation	5/194 (2.6%)		3/191 (1.6%)
Affect lability	4/194 (2.1%)		1/191 (0.5%)

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.