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.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 192
- 试验地点
- 11
- 主要终点
- Mean change in QT interval and heart rate on ECG; body weight, BMI, lab parameters
研究概览
简要总结
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 extrapyramidal side effects except for akathisia, despite its potent D2 antagonistic 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, the use 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or female patients between 18 and 65 years (inclusive).
- •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.
- •Patient is newly diagnosed with acute schizophrenia.
- •Patient has a PANSS total score ≥ 75 at the time of screening.
- •Patient has a score ≥ 4 (moderate) on 2 or more of the following PANSS items: Delusions, Conceptual disorganization, Hallucinations and Suspiciousness/persecution.
- •Patient has a score ≥ 4 on the CGI-S at screening.
- •Female patients of child bearing potential should have negative Urine Pregnancy Test (UPT) at the time of screening.
- •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.
排除标准
- •Elderly patients with dementia-related psychosis.
- •Diagnosis of mental retardation or other cognitive disorder
- •Any other Axis I psychiatric diagnosis.
- •Patient is currently on any anti-psychotic drug therapy.
- •Patient is considered by the investigator to be at imminent risk of suicide or injury to self, others or property.
- •Clinically significant suicidal or homicidal behavior or attempts within past 6 months.
- •Female patient has a positive pregnancy test at screening, is pregnant or lactating, or is planning to become pregnant during the study period.
- •Patient has received clozapine for refractory psychosis and/or patient has been treated with clozapine (for any reason) within 4 months of randomization.
- •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.
- •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.
- •Patient requires treatment with a drug that prolongs the QT interval corrected for individual heart rate (QTc interval).
- •History of Neuroleptic Malignant Syndrome (NMS).
- •History of Orthostatic Hypotension and Syncope.
- •History of Diabetes Mellitus.
- •Patient has a history of hyperprolactinemia (prolactin concentration >100ng/mL at screening) or pituitary adenoma.
- •Patient has a history of leukopenia, neutropenia and/or agranulocytosis.
- •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.
- •Patients who have received or are currently on depot neuroleptics.
- •Alcohol or substance dependence within the past 12 months or abuse within the past 3 months.
- •Known hypersensitivity to any drug that will be administered during the study.
- •Inability to comply with the protocol requirements.
结局指标
主要结局
Mean change in QT interval and heart rate on ECG; body weight, BMI, lab parameters
时间窗: 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]
Mean change in vital parameters
时间窗: 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]
EFFICACY:
时间窗: 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]
Mean change in total score of Positive and Negative Symptom Scale (PANSS)
时间窗: 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]
Proportion of treatment ‘Responders’ and ‘Non-Responders’ (Responders defined as patients reporting improvement of at least 28% on PANSS score)
时间窗: 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]
SAFETY:
时间窗: 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]
Proportion of patients reporting AE/ SAE
时间窗: 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]
Mean change in Extrapyramidal symptoms on Modified Simpson-Angus Scale (MSAS)
时间窗: 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]
次要结局
- 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)