CTRI/2014/04/004521 [Registered on: 03/04/2014] Trial Registered Prospectively
Last Modified On:
30/11/2018
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
A clinical study of two drugs, Lurasidone and Quetiapine, in newly diagnosed patients of Acute Schizophrenia.
Scientific Title of Study
An Active-Control, Open label, Comparative, Randomized, 3-arm, Parallel group, Multicenter, Phase-III Clinical Study to evaluate the Efficacy and Safety of two doses of Lurasidone when compared with Quetiapine in newly diagnosed patients of Acute Schizophrenia.
Ethics Committee, Osmania Medical College, Hyderabad
Submittted/Under Review
Hatkesh Healthcare Foundation Ethics Committee
Approved
Institutional Ethics Committee Peerless Hospital and B.K Roy Research Centre
Approved
Institutional Ethics Committee, Dept. of Pharmacology, JIPMER, Puducherry
Approved
Institutional Ethics Committee, Governemnt Medical College & Hospital
Approved
Institutional Ethics Committee, Hi-Tech Medical College & Hospital
Approved
Institutional Ethics Committee, the Calcutta Medical Research Institute
Submittted/Under Review
Medilink Ethics Committee
Approved
Swastik Bio Ethics Committee,
Submittted/Under Review
The Institutional Ethics Committee for MV Hospital and Research Centre
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
Newly diagnosed patients of Acute Schizophrenia,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Tablet Lurasidone 40 mg OD
40 mg tablet to be taken once daily with meals (more than 350 calories) for 42 days
Intervention
Tablet Lurasidone 80 mg OD
80 mg tablet to be taken once daily with meals (more than 350 calories) for 42 days
Comparator Agent
Tablet Quetiapine 200 mg OD
25 mg tablet to be taken twice daily for the first two days [day 1 and day 2], titrated to 50 mg tablet to be taken twice daily for the next two days [day 3 and day 4], eventually titrated to 200 mg tablet to be taken once daily for the next 38 days [day 5 through day 42]
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or female patients between 18 and 65 years (inclusive).
2. Patient meets DSM-IV criteria for primary diagnosis of Schizophrenia as established by clinical interview using M.I.N.I. (Mini International Neuropsychiatric Interview) diagnostic interview.
3. Patient is newly diagnosed with acute schizophrenia.
4. Patient has a PANSS total score ≥ 75 at the time of screening.
5. Patient has a score ≥ 4 (moderate) on 2 or more of the following PANSS items: Delusions, Conceptual disorganization, Hallucinations and Suspiciousness/persecution.
6. Patient has a score ≥ 4 on the CGI-S at screening.
7. Female patients of child bearing potential should have negative Urine Pregnancy Test (UPT) at the time of screening.
8. Patient or patient’s legally acceptable representative willing to sign the Informed Consent Document.
9.Patient willing and able to participate in all aspects of the core study, including use of oral medication, completion of subjective evaluations, and compliance with protocol requirements
ExclusionCriteria
Details
1. Elderly patients with dementia-related psychosis.
2. Diagnosis of mental retardation or other cognitive disorder
3. Any other Axis I psychiatric diagnosis.
4. Patient is currently on any anti-psychotic drug therapy.
5. Patient is considered by the investigator to be at imminent risk of suicide or injury to self, others or property.
6. Clinically significant suicidal or homicidal behavior or attempts within past 6 months.
7. Female patient has a positive pregnancy test at screening, is pregnant or lactating, or is planning to become pregnant during the study period.
8. Patient has received clozapine for refractory psychosis and/or patient has been treated with clozapine (for any reason) within 4 months of randomization.
9. Patient has received treatment with mood stabilizers or antidepressants within 1 week, fluexine hydrochloride at any time within 1 month or a monoamine oxidase (MAO) inhibitor with 3 weeks of randomization.
10. Presence of abnormal ECG parameters or significant cardiac disease, including uncompensated congestive heart failure, myocardial infarction within the past 6 months or known history of congenital long QT syndrome.
11. Patient requires treatment with a drug that prolongs the QT interval corrected for individual heart rate (QTc interval).
12. History of Neuroleptic Malignant Syndrome (NMS).
13. History of Orthostatic Hypotension and Syncope.
14. History of Diabetes Mellitus.
15. Patient has a history of hyperprolactinemia (prolactin concentration >100ng/mL at screening) or pituitary adenoma.
16. Patient has a history of leukopenia, neutropenia and/or agranulocytosis.
17. Patients who are currently or who will require treatment with strong CYP3A4 inhibitors (e.g., ketoconazole) or strong CYP3A4 inducers (e.g., rifampin) during the study.
18. Patients who have received or are currently on depot neuroleptics.
19. Any significant systemic disease, endocrine or metabolic abnormalities.
20. Alcohol or substance dependence within the past 12 months or abuse within the past 3 months.
21. Known hypersensitivity to any drug that will be administered during the study.
22. Inability to comply with the protocol requirements.
23. Participation in any other clinical trial within 3 months of registering in this trial.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
EFFICACY:
Mean change in total score of Positive and Negative Symptom Scale (PANSS)
Proportion of treatment ‘Responders’ and ‘Non-Responders’ (Responders defined as patients reporting improvement of at least 28% on PANSS score)
SAFETY:
Proportion of patients reporting AE/ SAE
Mean change in Extrapyramidal symptoms on Modified Simpson-Angus Scale (MSAS)
Mean change in QT interval and heart rate on ECG; body weight, BMI, lab parameters
Mean change in vital parameters
EFFICACY:
Baseline to each post randomization visit [Days 3, 5, 8, 15, 29 and 43]
On Day 43 as compared to baseline
SAFETY:
Each post randomization visit [Days 3, 5, 8, 15, 29 and 43]
Baseline to each post randomization visit [Days 3, 5, 8, 15, 29 and 43]
Baseline to end of protocol therapy [Day 43]
Baseline to each post randomization visit [Days 3, 5, 8, 15, 29 and 43]
Secondary Outcome
Outcome
TimePoints
Mean change in the Clinical Global Impression – Severity Scale (CGI-S) score
Baseline to Day 8, Day 15, Day 29, and Day 43
Mean score of Clinical Global Impression – Global Improvement
At Day 8, Day 15, Day 29, and Day 43
Target Sample Size
Total Sample Size="192" Sample Size from India="192" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
Lurasidone is an atypical antipsychotic used for the treatment of Schizophrenia in adults. Lurasidone alleviates both positive (e.g., hallucinations, delusions) and negative (e.g., apathy, emotional withdrawal) symptoms of schizophrenia without inducing extrapyramidalsideeffectsexceptforakathisia,despiteitspotentD2antagonistic actions. Lurasidone may be useful for treating cognitive and memory deficits seen in schizophrenia for several reasons:
1.Unlike many other antipsychotics, Lurasidone does not block the muscarinic acetylcholine receptors, an action well-known to impair learning and memory.
2.Lurasidone has prominent activity at 5-HT1A, 5-HT2A, 5-HT7, and α2C-adrenergic receptors, all of which have been implicated in enhancement of cognitive function if modulated properly.
3.Due to its low liability for extrapyramidal symptoms, Lurasidone is unlikely to require co-administration of anticholinergic, which impair cognition in their own right. In animal studies, Lurasidone was found to be superior to all of the other antipsychotics examined in reversing dizocilpine-induced learning and memory impairment.
The incidence of the Schizophrenia is relatively low (median value 15.2 per 100,000 persons per year), the condition is one of the major contributors to the global burden of disease. The substantial burden of disease is a reflection of two features of schizophrenia:
a.The disorder usually has its onset in early adulthood, and
b.Despite optimal treatment, approximately two-thirds of affected individuals have persisting or fluctuating symptoms.
Quetiapine Tablets are an atypical antipsychotic. Quetiapine is indicated for the treatment of schizophrenia. Quetiapine has relatively high side effects than Lurasidone. Quetiapine is the standard treatment for Schizophrenia.However,theuse of Quetiapine in treatment of Schizophrenia has started declining due to incidence of adverse effects in long term, as well as symptom rebound on withdrawal of the drug.