A Prospective, Matched-Control, Randomized, Open-Label, Flexible-Dose, Study in Subjects With Recent-Onset Schizophrenia or Schizophreniform Disorder to Compare Disease Progression and Disease Modification Following Treatment With Paliperidone Palmitate Long-Acting Injection or Oral Antipsychotics
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 337
- 主要终点
- Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score
研究概览
简要总结
The purpose of the study is to compare effectiveness of paliperidone palmitate (PP: paliperidone palmitate once-monthly and 3-month injections) versus oral antipsychotic (OAP [that is oral paliperidone extended release {ER}, oral risperidone, or another OAP]) in delaying time to treatment failure. The study will also evaluate changes in cognition, functioning, brain intracortical myelin (ICM) volume following treatment with PP compared with OAP in participants with recent-onset schizophrenia or schizophreniform disorder.
详细描述
A Prospective, matched-control, Randomized (assignment of study drug by chance), open-label, flexible-dose, study in participants with recent-onset schizophrenia or schizophreniform disorder to compare disease progression and disease modification following treatment with PP long-acting injection (once-monthly followed by 3-month injections) or OAP (Any of the following 7 OAPs are permitted: aripiprazole, haloperidol, olanzapine, paliperidone ER, perphenazine, quetiapine, and risperidone). The study consists of 3 parts. Part-1 (Oral Run-In Phase), Part-2 (Disease Progression) and Part-3 (Extended Disease Progression and Disease Modification) with unique endpoints. Screening period will be up to 4 Weeks. Duration of Parts will be as: 2 months for Part-1, 9 months for Part-2 and Part-3. All participants will initially receive oral paliperidone ER or oral risperidone in Part-1. After paliperidone/risperidone treatment in Part-1, participants will be randomized into 1:2 ratio to receive PP or OAP in Part-2. Participants who complete Part-2 will enter into Part-3 wherein OAP group participants of Part-2 will be re-randomized into 1:1 ratio to OAP-OAP group and OAP-PP group, and PP group will continue without further randomization. Treatment failures will be evaluated in Part-2 and Part-3 of the study. Also changes in cognition, functioning, brain intracortical myelin (ICM) volume will be evaluated in the study. Participants' safety will be monitored throughout. Healthy controls (comparable in age, sex, race, and highest parental education to the treated participants) were recruited at each of the 3 MRI centers as controls for the MRI machine calibration for the duration of the study. These healthy controls were to undergo MRI assessments, but were not otherwise involved with the study and did not receive study medication. No safety or efficacy data were collected for these healthy controls.
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
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant must have a current diagnosis of schizophrenia (295.90) or schizophreniform disorder (295.40) as defined by Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and confirmed by the Structured Clinical Interview for DSM-5 Disorders (SCID) with a first psychotic episode within the last 24 months prior to the screening visit
- •Participant requires treatment with an antipsychotic medication
- •Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study
- •Participant must have available a designated individual (example, family member, significant other, friend) who has knowledge of the participant and is generally aware of the participants daily activities, and who agrees to let the study site personnel know of changes in the participants circumstances when the participant is not able to provide this information. The designated individual must sign an informed consent form
- •Participant is anticipated to have a stable place of residence for the duration of the trial
排除标准
- •Participant has a current DSM-5 diagnosis of dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, autistic disorder, or intellectual disabilities
- •Participant meets the DSM-5 definition of moderate or severe substance use disorder (except for nicotine) within 2 months prior to Screening
- •Participant has a history of neuroleptic malignant syndrome
- •Participant has received long-acting injectable (LAI) medication within 2 injection cycles prior to the Screening visit
- •Participant has mental retardation, defined as pre-morbid intelligence quotient (IQ) as measured by Wechsler Test of Adult Reading at Screening less than (<) 70
研究组 & 干预措施
Part-1: Oral Antipsychotics (OAP)
All Participants will receive Paliperidone Extended Release (ER) 1.5 to 12 milligram (mg) or risperidone 1 to 6 mg once daily orally for 2 months. Subjects who tolerate paliperidone ER/risperidone but find it inadequately efficacious after treatment for an adequate duration at an adequate dosage (per clinical judgment), may be switched to another protocol-specified OAP at the discretion of the investigator.
干预措施: Aripiprazole (Drug)
Part-1: Oral Antipsychotics (OAP)
All Participants will receive Paliperidone Extended Release (ER) 1.5 to 12 milligram (mg) or risperidone 1 to 6 mg once daily orally for 2 months. Subjects who tolerate paliperidone ER/risperidone but find it inadequately efficacious after treatment for an adequate duration at an adequate dosage (per clinical judgment), may be switched to another protocol-specified OAP at the discretion of the investigator.
干预措施: Haloperidol (Drug)
Part-1: Oral Antipsychotics (OAP)
All Participants will receive Paliperidone Extended Release (ER) 1.5 to 12 milligram (mg) or risperidone 1 to 6 mg once daily orally for 2 months. Subjects who tolerate paliperidone ER/risperidone but find it inadequately efficacious after treatment for an adequate duration at an adequate dosage (per clinical judgment), may be switched to another protocol-specified OAP at the discretion of the investigator.
干预措施: Olanzapine (Drug)
Part-1: Oral Antipsychotics (OAP)
All Participants will receive Paliperidone Extended Release (ER) 1.5 to 12 milligram (mg) or risperidone 1 to 6 mg once daily orally for 2 months. Subjects who tolerate paliperidone ER/risperidone but find it inadequately efficacious after treatment for an adequate duration at an adequate dosage (per clinical judgment), may be switched to another protocol-specified OAP at the discretion of the investigator.
干预措施: Oral Paliperidone ER (Drug)
Part-1: Oral Antipsychotics (OAP)
All Participants will receive Paliperidone Extended Release (ER) 1.5 to 12 milligram (mg) or risperidone 1 to 6 mg once daily orally for 2 months. Subjects who tolerate paliperidone ER/risperidone but find it inadequately efficacious after treatment for an adequate duration at an adequate dosage (per clinical judgment), may be switched to another protocol-specified OAP at the discretion of the investigator.
干预措施: Perphenazine (Drug)
Part-1: Oral Antipsychotics (OAP)
All Participants will receive Paliperidone Extended Release (ER) 1.5 to 12 milligram (mg) or risperidone 1 to 6 mg once daily orally for 2 months. Subjects who tolerate paliperidone ER/risperidone but find it inadequately efficacious after treatment for an adequate duration at an adequate dosage (per clinical judgment), may be switched to another protocol-specified OAP at the discretion of the investigator.
干预措施: Quetiapine (Drug)
Part-1: Oral Antipsychotics (OAP)
All Participants will receive Paliperidone Extended Release (ER) 1.5 to 12 milligram (mg) or risperidone 1 to 6 mg once daily orally for 2 months. Subjects who tolerate paliperidone ER/risperidone but find it inadequately efficacious after treatment for an adequate duration at an adequate dosage (per clinical judgment), may be switched to another protocol-specified OAP at the discretion of the investigator.
干预措施: Oral Risperidone (Drug)
Part-2: Paliperidone Palmitate (PP)
Participants who will complete Part-1 will be randomized to receive oral Paliperidone Palmitate (PP) treatment. Participants will receive 5 doses of PP1M (paliperidone palmitate once-monthly injection). First dose at a starting dose of 234 mg on Day 1 and thereafter second dose in second week and then, every month up to Day 92. Participants will be subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M. Participants receiving PP3M may go back to treatment with PP1M (monthly injections of 78, 117, 156 or 234 mg, flexibly dosed) for further dose adjustment or for the duration of the study with the approval of the medical monitor.
干预措施: Paliperidone Palmitate Injection (PP1M) (Drug)
Part-2: Paliperidone Palmitate (PP)
Participants who will complete Part-1 will be randomized to receive oral Paliperidone Palmitate (PP) treatment. Participants will receive 5 doses of PP1M (paliperidone palmitate once-monthly injection). First dose at a starting dose of 234 mg on Day 1 and thereafter second dose in second week and then, every month up to Day 92. Participants will be subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M. Participants receiving PP3M may go back to treatment with PP1M (monthly injections of 78, 117, 156 or 234 mg, flexibly dosed) for further dose adjustment or for the duration of the study with the approval of the medical monitor.
干预措施: Paliperidone Palmitate Injection (PP3M) (Drug)
Part-2: OAP
Participants who will complete Part-1 will be randomized to receive Oral Antipsychotics for 9 months.
干预措施: Aripiprazole (Drug)
Part-2: OAP
Participants who will complete Part-1 will be randomized to receive Oral Antipsychotics for 9 months.
干预措施: Haloperidol (Drug)
Part-2: OAP
Participants who will complete Part-1 will be randomized to receive Oral Antipsychotics for 9 months.
干预措施: Olanzapine (Drug)
Part-2: OAP
Participants who will complete Part-1 will be randomized to receive Oral Antipsychotics for 9 months.
干预措施: Oral Paliperidone ER (Drug)
Part-2: OAP
Participants who will complete Part-1 will be randomized to receive Oral Antipsychotics for 9 months.
干预措施: Perphenazine (Drug)
Part-2: OAP
Participants who will complete Part-1 will be randomized to receive Oral Antipsychotics for 9 months.
干预措施: Quetiapine (Drug)
Part-2: OAP
Participants who will complete Part-1 will be randomized to receive Oral Antipsychotics for 9 months.
干预措施: Oral Risperidone (Drug)
Part-3: PP - PP
Participants who will complete Part-2 (with PP treatment) will continue to receive Paliperidone Palmitate for 9 months.
干预措施: Paliperidone Palmitate Injection (PP3M) (Drug)
Part-3: OAP - Delayed Start Paliperidone Palmitate (PP)
Participants who will complete Part-2 (with OAP treatment) will be randomized to receive PP treatment for 9 months. PP treatment includes PP1M and PP3M. Participants will be subsequently switched to PP3M following a minimum of 5 injections of PP1M. Participants receiving PP3M may go back to treatment with PP1M (monthly injections of 78, 117, 156 or 234 mg, flexibly dosed) for further dose adjustment or for the duration of the study with the approval of the medical monitor.
干预措施: Paliperidone Palmitate Injection (PP1M) (Drug)
Part-3: OAP - Delayed Start Paliperidone Palmitate (PP)
Participants who will complete Part-2 (with OAP treatment) will be randomized to receive PP treatment for 9 months. PP treatment includes PP1M and PP3M. Participants will be subsequently switched to PP3M following a minimum of 5 injections of PP1M. Participants receiving PP3M may go back to treatment with PP1M (monthly injections of 78, 117, 156 or 234 mg, flexibly dosed) for further dose adjustment or for the duration of the study with the approval of the medical monitor.
干预措施: Paliperidone Palmitate Injection (PP3M) (Drug)
Part-3: OAP - OAP
Participants who will complete Part-2 (with OAP treatment) will be randomized to receive OAP treatment for additional 9 months.
干预措施: Aripiprazole (Drug)
Part-3: OAP - OAP
Participants who will complete Part-2 (with OAP treatment) will be randomized to receive OAP treatment for additional 9 months.
干预措施: Haloperidol (Drug)
Part-3: OAP - OAP
Participants who will complete Part-2 (with OAP treatment) will be randomized to receive OAP treatment for additional 9 months.
干预措施: Olanzapine (Drug)
Part-3: OAP - OAP
Participants who will complete Part-2 (with OAP treatment) will be randomized to receive OAP treatment for additional 9 months.
干预措施: Oral Paliperidone ER (Drug)
Part-3: OAP - OAP
Participants who will complete Part-2 (with OAP treatment) will be randomized to receive OAP treatment for additional 9 months.
干预措施: Perphenazine (Drug)
Part-3: OAP - OAP
Participants who will complete Part-2 (with OAP treatment) will be randomized to receive OAP treatment for additional 9 months.
干预措施: Quetiapine (Drug)
Part-3: OAP - OAP
Participants who will complete Part-2 (with OAP treatment) will be randomized to receive OAP treatment for additional 9 months.
干预措施: Oral Risperidone (Drug)
结局指标
主要结局
Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score
时间窗: Baseline and 18 Months
The MATRICS Consensus Cognitive Battery is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The composite score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score and composites scores. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.
Part-2 (Disease Progression): Time to First Treatment Failure
时间窗: From Day 1 up to 9 Months
Treatment failure is defined as the time from participant's randomization to first treatment failure, which was a composite endpoint consisting of any of the following: 1) Psychiatric hospitalization due to worsening symptoms; 2) Any deliberate self-injury, suicidal ideation or behavior, homicidal ideation or violent behavior that is clinically significant and needs immediate intervention as determined by the study physician; 3) New arrest/incarceration; 4) Discontinuation of antipsychotic treatment due to inadequate efficacy as determined by the study physician; 5) Discontinuation of antipsychotic treatment due to safety or tolerability as determined by the study physician; 6) Treatment supplementation with another antipsychotic due to inadequate efficacy as determined by the study physician; 7) Increase in the level of psychiatric services in order to prevent imminent psychiatric hospitalization as determined by the study physician.
Part 3 (Disease Modification): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score
时间窗: Baseline and Day 260
The MATRICS Consensus Cognitive Battery is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The composite score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score and composites scores. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.
次要结局
- Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain(Baseline and Day 260)
- Part 2 (Disease Progression): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score(Baseline and Month 9)
- Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain(Baseline and Day 260)
- Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score(Baseline and Month 9)
- Part 2 (Disease Progression): Change From Baseline in Adjusted Intracortical Myelin (ICM) Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)(Baseline and Day 260)
- Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain(Baseline and Day 260)
- Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain(Baseline and Day 260)
- Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain(Baseline and Day 260)
- Part 3 (EDP): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score(Baseline and 18 Months)
- Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain(Baseline and 18 Months)
- Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain(Baseline and 18 Months)
- Part 3 (Disease Modification): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (SE MRI)(Baseline and Month 9 of Part 3)
- Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain(Baseline and Day 260)
- Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain(Baseline and Day 260)
- Part 2 (Disease Progression): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score(Baseline, up to 9 Months of Part 2)
- Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score(Baseline and endpoint Part 2 (up to 9 Months))
- Part 3 (EDP): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)(Baseline and 18 Months)
- Part 3 (EDP): Time to First Treatment Failure(From Day 1 Up to 18 Months)
- Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain(Baseline and 18 Months)
- Part 2 (Disease Progression): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by Clinician-Rated Dimensions of Psychosis Symptom Severity Scale (CRDPSS)(Baseline, up to 9 Months)
- Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain(Baseline and 18 Months)
- Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain(Baseline and 18 Months)
- Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score(Baseline, up to 18 Months)
- Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain(Baseline and 18 Months)
- Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS(Baseline, up to 18 Months)
- Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain(Baseline and 18 Months)
- Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score(Baseline, up to 18 Months)
- Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score(Month 9 of Part 3)