A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Monotherapy Study to Evaluate Efficacy of Roluperidone on Negative Symptoms in Adult Subjects With Schizophrenia, Followed by a 52-Week, Randomized, Double-Dummy Phase to Evaluate the Relapse Rate of Roluperidone and Antipsychotic Medications
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 380
- 试验地点
- 13
- 主要终点
- Change from Baseline to Week 12 in Marder Negative Symptoms Factor Score (NSFS)
研究概览
简要总结
Evaluate the efficacy, as well as safety and pharmacokinetics, of Roluperidone in improving the negative symptoms of schizophrenia in adult subjects in Phase A of study, followed by Phase B of study to evaluate the relapse rate of Roluperidone and antipsychotic medications.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •* Subject and subject's legal representative, if applicable, provided informed consent prior to the initiation of any study related procedures, and the subject is judged by the investigator as being capable of understanding the study requirements.
- •* Male or female, 18 to 55 years of age, inclusive, and body mass index (BMI) \ 20 on the PANSS negative subscale score (\[sum of N1+N2+N3+N4+N5+N6+N7\]) at Screening (Visit 1) and Baseline (Visit 3) AND \< 4 points absolute difference between Visits 1 and 3.
- •* Must discontinue any psychotropic medications by or at the beginning of the washout phase (Day -2). The rate of washout/discontinuation of psychotropic medications during the Screening period should be gradual in order to reduce the risk of psychotropic withdrawal symptoms but remains at the discretion of the investigator.
- •* Has no history of violence against self or others.
- •* Female subject, if not of childbearing potential, defined as a woman who is post-menopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy).
- •* Female subject, if of childbearing potential, must test negative for pregnancy and must use 2 approved methods of highly effective contraception.
- •* Must be normal or ultrarapid metabolizer for cytochrome P450 (CYP) 2D6, defined as having an activity score (AS) of \>/= 1.25 as determined by study-specific genotyping test before the first dose of study drug dose is administered.
- •* Subject and the caregiver are considered by the investigator to be reliable and likely to cooperate with the assessment procedures.
排除标准
- •* Current major depressive disorder, bipolar disorder, panic disorder, obsessive compulsive disorder, or intellectual disability (intellectual developmental disorder diagnosed by age 14), drugs or alcohol addiction.
- •* PANSS item score of \> 4 on any of the following items: P4 Excitement/Hyperactivity; P6 Suspiciousness/persecution; P7 Hostility; G8 Uncooperativeness; G14 Poor impulse control.
- •* A Calgary Depression Scale for Schizophrenia (CDSS) total score \> 6.
- •* A score of \>/= 2 on any 2 items of items 1, 2, or 3, or a score of \>/= 3 on item 4 of the Barnes Akathisia Rating Scale (BARS).
- •* Subject's condition is due to direct physiological effects of a substance (e.g., a drug of abuse, or medication) or a general medical condition.
- •* Current or recent history of serious suicidal behavior within the past 1 year.
- •* History of substance use disorder within 3 months of the Screening visit (excluding caffeine and cigarette smoking).
- •* Positive urine drug screen for any drug of abuse (cocaine, methadone, amphetamines, cannabinoids, opiates, benzodiazepines, and barbiturates), tricyclic antidepressants (TCA), and alcohol (except for prescription benzodiazepines).
- •* Cannot be discontinued from psychotropics.
- •* Received clozapine within 6 months of the Screening visit except when used for insomnia at doses \ 3 × the upper limit of normal \[ULN\], total bilirubin \> 2 × ULN, or alkaline phosphatase \> 1.5 × ULN), or physical examination not resolved by the Baseline visit which according to Investigator can interfere with study participation.
- •* Safety laboratory results from the Pretreatment Phase show one or more of the following: potassium \< 3.4 mmol/L, calcium \< 2.07 mmol/L, or magnesium \< 0.70 mmol/L.
- •* Current systemic infection (e.g., Hepatitis B, Hepatitis C, human immunodeficiency virus \[HIV\], tuberculosis). A subject with positive Hepatitis B core antibody test and negative Hepatitis B Surface Antigen (HBsAg) may be included in the study if aminotransferase levels (alanine aminotransferase/ serum glutamate pyruvate transaminase \[ALT/SGPT\] and aspartate aminotransferase/ serum glutamic oxaloacetic transaminase \[AST/SGOT\]) do not exceed 2 × ULN.
- •* Requires or may require concomitant treatment with any other medication likely to increase QT interval (e.g., paroxetine, fluoxetine, duloxetine, amiodarone).
- •* Requires medication inhibiting CYP2D6.
- •* Clinically significant ECG abnormality that could be a safety issue in the study, including QT interval value corrected for heart rate using the Fridericia's formula (QTcF) \> 430 msec for males and \> 450 msec for females.
- •* Familial or personal history of long QT syndrome or with another risk factor for Torsade de Pointes.
- •* History of myocardial infarction based on medical history or ECG findings at Screening.
- •* Syncope.
- •* Woman of child-bearing potential, or man, who is unwilling or unable to use accepted methods of birth control.
- •* Woman with a positive pregnancy test, is lactating, or is planning to become pregnant during the study.
- •* Participated in another clinical study that was completed within 6 months prior to Screening or has previously participated in \> 2 clinical studies with experimental medication within the past 2 years.
研究组 & 干预措施
Roluperidone to Antipsychotic
Roluperidone 64 mg administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).
干预措施: aripiprazole (Drug)
Placebo to Roluperidone
Placebo administered as an oral dose daily from Day 1 to Week 12 (Phase A), then Roluperidone 64 mg administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).
干预措施: Placebo (Drug)
Roluperidone to Roluperidone
Roluperidone 64 mg administered as an oral dose daily from Day 1 to Week 12 (Phase A), then Roluperidone 64 mg administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).
干预措施: Roluperidone (Drug)
Placebo to Antipsychotic
Placebo administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).
干预措施: Placebo (Drug)
Placebo to Roluperidone
Placebo administered as an oral dose daily from Day 1 to Week 12 (Phase A), then Roluperidone 64 mg administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).
干预措施: Roluperidone (Drug)
Placebo to Antipsychotic
Placebo administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).
干预措施: olanzapine (Drug)
Roluperidone to Antipsychotic
Roluperidone 64 mg administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).
干预措施: Roluperidone (Drug)
Placebo to Antipsychotic
Placebo administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).
干预措施: risperidone (Drug)
Placebo to Antipsychotic
Placebo administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).
干预措施: aripiprazole (Drug)
Roluperidone to Antipsychotic
Roluperidone 64 mg administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).
干预措施: risperidone (Drug)
Roluperidone to Antipsychotic
Roluperidone 64 mg administered as an oral dose daily from Day 1 to Week 12 (Phase A), then antipsychotic (risperidone 4 mg, aripiprazole 10 mg, or olanzapine 10 mg) administered as an oral dose daily from Week 12 +1 day to Week 64 (Phase B).
干预措施: olanzapine (Drug)
结局指标
主要结局
Change from Baseline to Week 12 in Marder Negative Symptoms Factor Score (NSFS)
时间窗: Phase A: Screening, Baseline, Weeks 2, 4, 8, 12
The Marder Negative Symptoms Factor Score (NSFS) derived from the complete Positive and Negative Syndrome Scale (PANSS) has been the most frequently used scale in schizophrenia clinical studies focusing on negative symptoms. The PANSS measures comprehensive psychiatric symptoms, including positive, negative, and general symptoms. The full PANSS rates the patient on 30 different symptoms from 1 (absent) to 7 (extreme) based on an interview as well as reports of family members or primary care hospital workers. Negative symptoms will be defined by PANSS negative subscore (N1+N2+N3+N4+N5+N6+N7). Higher scores indicate more severe symptoms.
次要结局
- Change from Baseline to Week 12 in the Personal and Social Performance (PSP) Total Score(Phase A: Baseline and Weeks 4, 8, 12)
- Change from Baseline to Week 12 in Clinical Global Impression of Severity (CGI-S)(Phase A: Screening, Baseline, and Weeks 2, 4, 8, 12)
- Change from Baseline to Week 12 in Clinical Global Impression - Severity (CGI-S) Scale(Phase A: Screening, Baseline, and Weeks 2, 4, 8, 12)