Phase 3 long-term safety, tolerability and effectiveness of lurasidone in subjects with schizophrenia or schizoaffective disorder

ISRCTN	ISRCTN97049967
DOI	https://doi.org/10.1186/ISRCTN97049967
ClinicalTrials.gov number	NCT00641745
Secondary identifying numbers	D1050237

Submission date: 11/04/2008
Registration date: 17/04/2008
Last edited: 22/03/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Ms Shelda Alcock
Scientific

Dainippon Sumitomo Pharma Europe Ltd
1st Floor
Southside
97-105 Victoria Street
London
SW1E 6QT
United Kingdom

Study information

Study design	Randomised active-comparator controlled trial.
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format. Please use the contact details below to request a patient information sheet.
Scientific title	Phase 3 long-term safety, tolerability and effectiveness of lurasidone in subjects with schizophrenia or schizoaffective disorder: a randomised, active comparator-controlled trial
Study objectives	To assess long-term safety, tolerability and effectiveness of lurasidone over a 12-month double-blind period in clinically stable out-patients with chronic schizophrenia or schizoaffective disorder, followed by a 6-month open label extension phase. Risperidone will be used as active comparator.
Ethics approval(s)	Argentina: Ethics Committee for Research on Mental Illness (Comite de Bioetica e Investigacion-Funacion para el Estudio y Tratamiento de las Enfermedades Mentales). Date of approval: 13/03/2008 Brazil: Ethics committee for Research at the Mario Kroeff Hospital (Comite de Etica em Pesquisa de Hospital Mario Kroeff). Date of approval: 28/02/2008 Chile: Ethics Committee of the South Metropolitan Health Service (Comite Etico-Cientifico Servidio de Salud Metropolitano Sur). Date of approval: 19/03/2008 South Africa: 1. Ethics Committee, University of the Free State. Date of approval: 11/03/2008 (ref: ETOVS NR51/08) 2. Ethics Committee, Pharma-Ethics (Pty), Ltd. Date of approval: 16/04/2008 (ref: 08032544) Thailand: The Ethical Review Committee for Research in Human Subjects. Date of approval: 08/04/2008 Ethics approval pending from: Croatia: Central Ethics Committee. Approval expected on 30/08/2008 Israel: Helsinki Committee of the Shalvata Mental Health Centre. Approval expected on 16/04/2008
Health condition(s) or problem(s) studied	Schizophrenia
Intervention	This trial is in two stages: 12-month double-blind treatment of lurasidone HCl 40 mg oral tablets with matching placebo, and risperidone over-encapsulated oral capsules (2, 4 or 6 mg) with matching placebo in double-dummy design. Once-daily dosing for all medications (Stage 1). Followed by 6-month open-label extension phase (Stage 2). During the open-label period all participants will (after a single-blind, 3 day placebo washout) initially receive lurasidone HCl 80 mg/day, after 7 days of study medication the dose may be adjusted between 40-120 mg/day.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Lurasidone, risperidone
Primary outcome measure	Assess long-term safety and tolerability of lurasidone by measuring proportion of subjects with adverse events and serious adverse events. These will be assessed at 12 months. Safety will also be assessed at 18 months.
Secondary outcome measures	1. To measure changes in the following: 1.1. Weight at Screening, baseline, Week 12, Month 6, 9 and 12 and then monthly until 18 months 1.2. BMI at Screening, baseline, Week 12, Month 6, 9 and 12 and then monthly until 18 months 1.3. Waist circumference at baseline, 6, 12 and 18 months 1.4. Serum prolactin at Screening, baseline, 6 and 12 weeks, 6, 12, 13, 15 and 18 months 1.5. Testosterone at baseline, 6 and 12 weeks, 6, 12, 15 and 18 1.6. N-telopeptide (NTx) at Screening, baseline, 6, 9, 12, 15 and 18 months 1.7. Osteocalcin at Screening, baseline, 6, 9, 12, 15 and 18 months 1.8. Bone alkaline phosphatise at Screening, baseline, 6, 9, 12, 15 and 18 months 1.9. Parathyroid hormone (PTH) at Screening, baseline, 6, 9, 12, 15 and 18 months 1.10. ECG parameters at Screening, baseline, 7 days, 6 weeks, 6, 12 and 18 months 2. To evaluate long-term efficacy of lurasidone and risperidone by changes in the following at 12 months: 2.1. Positive and Negative Symptom Scale (PANSS) score 2.2. Clinical global impression of severity (CGI-S) score 2.3. Montgomery and Asberg Depression Rating Scale (MADRS) score 3. Demonstrate lurasidone is as effective as risperidone in maintaining clinical stability and preventing relapse, assessed at 12 months
Overall study start date	16/05/2008
Completion date	06/05/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	75 Years
Sex	Both
Target number of participants	600 patients
Key inclusion criteria	1. Aged between 18 and 75 years, both genders 2. Meets the Diagnostic and Statistical Manual of mental disorders fourth edition (DSM-IV) criteria for a primary diagnosis of schizophrenia 3. Judged by investigator to be clinically stable 8 weeks prior to baseline 4. Not pregnant, if of reproductive potential agrees to remain abstinent or use adequate and reliable contraception for duration of study 5. Tests negative for drug abuse at screening 6. Good physical health on the basis of medical history, physical examination and laboratory screening 7. Willing and able to comply with the protocol, including the inpatient requirements and outpatient visits 8. Provides written informed consent
Key exclusion criteria	1. Clinically significant medical condition that would pose a risk to subject in the study 2. Type 1 diabetes and insulin-dependent Type 2 diabetes 3. Chronic organic disease of the central nervous system 4. History of head injury resulting in attributable neuropsychiatric systems 5. History of malignancy <5 years prior to signing informed consent 6. Clinically significant history of alcohol abuse/alcoholism or drug abuse/dependence within last 6 months 7. History of macular or retinal pigmentary disease 8. History of stomach or intestinal surgery 9. History of previous psychosurgery 10. History of neuroleptic malignant syndrome 11. Severe tardive dyskinesia, severe chronic tardive dystonia or other severe chronic movement disorder 12. Clinically significant suicidal ideation, suicidal behaviour or violent behaviour in past 6 months. 13. Body mass index <18.5 or >40 kg/mg^2 14. Evidence of acute hepatitis, clinically significant chronic hepatitis or impaired hepatic function 15. Prolactin concentration >100 ng/mL at screening 16. Abnormal laboratory parameters indicating clinically significant medical condition 17. Resistant to antipsychotic treatment 18. Treatment with risperidone within 6 weeks prior to baseline 19. History of poor response to risperidone 20. Electroconvulsive therapy treatment within last 3 months or likely to require it during study 21. History of treatment with clozapine for refractory psychosis or clozapine treatment within 4 months of baseline visit 22. Treatment with mood stabilisers or antidepressants with 1 week, fluoxetine within 1 month 23. Received depot neuroleptics unless last injection at least 1 treatment cycle before randomisation 24. Subject does not require chronic treatment with antipsychotic drug 25. Subject has condition, therapy, laboratory abnormality which may affect results of/participation in study 26. History of hypersensitivity to risperidone 27. History or presence of abnormal electrocardiogram (ECG) which is clinically significant 28. Participation in study with investigational compound/device within 30 days of signing informed consent 29. Donation of blood products or has had phlebotomy of >300 mL within 8 weeks of signing informed consent 30. Previously screened or entered into antipsychotic medication withdrawal phase of this study more than 3 times 31. Routinely use anabolic steroids or require ongoing treatment with steroids 32. Past or current Cushing's disease, Addison's disease, growth hormone deficiency, hyperparathyroidism 33. Unlikely to adhere to study procedures, in investigator's opinion
Date of first enrolment	16/05/2008
Date of final enrolment	06/05/2010

Locations

Countries of recruitment

Argentina
Brazil
Chile
Croatia
England
Israel
South Africa
Thailand
United Kingdom

Study participating centre

Dainippon Sumitomo Pharma Europe Ltd

London
SW1E 6QT
United Kingdom

Sponsor information

Dainippon Sumitomo Pharma America Inc. (USA)
Industry

One Bridge Plaza
Suite 510
Fort Lee
New Jersey
07024
United States of America

Website	http://www.ds-pharma.co.jp/english
"ROR"	https://ror.org/04vwbmb32

Funders

Funder type

Industry

Dainippon Sumitomo Pharma Co. Ltd (Japan)
Private sector organisation / For-profit companies (industry)

Alternative name(s): Dainippon Sumitomo Pharma Co., Ltd.
Location: Japan

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results				No	No
Results article	results	01/05/2012		Yes	No

Editorial Notes

22/03/2016: added link to results - basic reporting.