A Double-blind, Randomized, Active-controlled, Parallel-group Study of Paliperidone Palmitate 6-Month Formulation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 841
- 试验地点
- 138
- 主要终点
- Time to Relapse During the Double-Blind (DB) Phase
研究概览
简要总结
The purpose of this study is to demonstrate that injection cycles consisting of a single administration of paliperidone palmitate 6-month (PP6M) are not less effective than 2 sequentially administered injections of paliperidone palmitate 3-month PP3M) (350 or 525 mg eq.) for the prevention of relapse in participants with schizophrenia previously stabilized on corresponding doses of paliperidone palmitate 1-month (PP1M) (100 or 150 mg eq.) or PP3M (350 or 525 mg eq.).
详细描述
The primary hypothesis of this study is that the efficacy of PP6M is non-inferior to PP3M for preventing relapse in participants with schizophrenia who were previously stabilized on corresponding doses of PP1M or PP3M. The study consists of mainly 3 phases: a screening phase (up to 28 days), a maintenance phase (of 1 or 3 months), and a double-blind phase (of 12 months [neither the researchers nor the participants know what treatment the participant is receiving]). Additional/conditional phases include a transition phase (before maintenance phase). Study evaluations include efficacy, pharmacokinetics, pharmacodynamics, and safety. The study duration will vary from approximately 13 months to 19 months.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must meet the diagnostic criteria for schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) for at least 6 months before screening
- •Must be receiving treatment with paliperidone palmitate (as either the paliperidone palmitate 1-month (PP1M) or paliperidone palmitate 3-month (PP3M) formulation), or injectable risperidone, or any oral antipsychotic
- •Must be able, in the opinion of the investigator, to discontinue any antipsychotic medication other than PP1M) or PP3M during the Screening Phase
- •Must have a full Positive and Negative Syndrome Scale (PANSS) score of less than (<) 70 points at screening
- •Must have a body mass index (BMI) between 17 and 40 kilogram (kg)/meter (m)^2 (inclusive) and must have a body weight of at least 47 kg at screening
- •Must be willing to receive gluteal injections of medication during the Double-blind Phase
- •Exclusion Criteria
- •Must not be receiving any form of involuntary treatment, such as involuntary psychiatric hospitalization, parole-mandated treatment, or court-mandated treatment
- •Must not have attempted suicide within 12 months before screening and must not be at imminent risk of suicide or violent behavior, as clinically assessed by the investigator at the time of screening
- •Must not have a DSM-5 diagnosis of moderate or severe substance use disorder (except for nicotine and caffeine) within 6 months of screening; however, acute or intermittent substance use prior to screening is not exclusionary, depending upon the clinical judgment of the investigator
- •Must not have a history of neuroleptic malignant syndrome or tardive dyskinesia
- •Must not have a history of intolerability or severe reactions to moderate or higher doses of antipsychotic medications and must not have any other factors that would, in the judgment of the investigator, indicate that treatment with moderate or higher doses of paliperidone palmitate would be intolerable or unsafe
排除标准
- 未提供
研究组 & 干预措施
PP1M/PP3M: Maintenance Phase
All the participants will receive only 1 dose of PP1M 100 or 150 mg eq. or PP3M 350 or 525 mg eq. The participants will precede from maintenance phase to double-blind phase.
干预措施: PP3M 350 mg eq. (Drug)
PP1M/PP3M: Maintenance Phase
All the participants will receive only 1 dose of PP1M 100 or 150 mg eq. or PP3M 350 or 525 mg eq. The participants will precede from maintenance phase to double-blind phase.
干预措施: PP3M 525 mg eq. (Drug)
PP3M: Double-Blind Phase
Participants will receive intramuscular injections of PP3M at dose of 350 mg eq. or 525 mg eq. in left gluteal muscle on Day 1 and 274 and right gluteal muscle on Day 92 and 183.
干预措施: PP3M 525 mg eq. (Drug)
PP1M: Transition Phase
Participants who previously have not achieved stability with moderate to higher doses of Paliperidone palmitate 1-month (PP1M) or Paliperidone palmitate 3-month (PP3M) will enter into a transition period of up to 4 months. During transition period participants will receive 1 to 5 injections of PP1M 50 to 100 milligrams equivalent (mg eq.). The participants who achieved stability (stability is defined as at least 3 months of injections with the last 2 doses being the same strength) with PP1M 100 mg eq. will precede from transition phase to maintenance phase.
干预措施: PP1M (Drug)
PP1M/PP3M: Maintenance Phase
All the participants will receive only 1 dose of PP1M 100 or 150 mg eq. or PP3M 350 or 525 mg eq. The participants will precede from maintenance phase to double-blind phase.
干预措施: PP1M (Drug)
PP6M or Placebo: Double-Blind Phase
Participants will receive intramuscular injection of PP6M in left gluteal muscle on Day 1 and right gluteal muscle on Day 183 with alternating placebo in right gluteal muscle on Day 92 and left gluteal muscle on Day 274.
干预措施: PP6M (Drug)
PP6M or Placebo: Double-Blind Phase
Participants will receive intramuscular injection of PP6M in left gluteal muscle on Day 1 and right gluteal muscle on Day 183 with alternating placebo in right gluteal muscle on Day 92 and left gluteal muscle on Day 274.
干预措施: Placebo (Other)
PP3M: Double-Blind Phase
Participants will receive intramuscular injections of PP3M at dose of 350 mg eq. or 525 mg eq. in left gluteal muscle on Day 1 and 274 and right gluteal muscle on Day 92 and 183.
干预措施: PP3M 350 mg eq. (Drug)
结局指标
主要结局
Time to Relapse During the Double-Blind (DB) Phase
时间窗: Up to 12 months of DB Phase
Time to relapse is time between participant randomization in DB Phase and first documentation of relapse event by end of Month 12 of DB phase. Relapse is defined as: a) Psychiatric hospitalization; b) Positive and Negative Syndrome Scale (PANSS) total score: Increase of 25 percentage (%), 10 point increase in PANSS for 2 analysis separated by 3-7 days if score was greater than (\>) 40, less than or equal to (\<=)40; c) Participants inflicted knowing self-injury/shown violent behavior leading to suicide, clinically significant injury to him/herself or other person/property; d) Participants had suicidal/homicidal ideation/violent behavior that was clinically significant as per investigator; e) PANSS items P1- delusions, P2- conceptual disorganization, P3-hallucinatory behavior, P6- suspiciousness/ persecution, P7-hostility, G8-uncooperativeness: score: greater than or equal to (\>=)5, \>=6 for 2 analysis separated by 3-7 days on any items if maximum score for PANSS: \<=3 or 4, respectively.
次要结局
- Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score(Baseline (DB) to 12 Months of DB Phase)
- Change From Baseline in the Clinical Global Impression - Severity (CGI-S) Score(Baseline (DB) to 12 Months of DB Phase)
- Change From Baseline in the Personal and Social Performance (PSP) Scale Total Score(Baseline (DB) to 12 Months of DB Phase)
- Percentage of Participants With Symptomatic Remission Based on PANSS Score During DB Phase(Up to 12 months of DB Phase)
- Change From Baseline in the Satisfaction With Participants in Social Roles (SPSR) Score(Baseline (DB) to 12 Months of DB Phase)
- Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score(Baseline (DB) to 12 Months of DB Phase)
- Change From Baseline in the Simpson-Angus Rating Scale (SAS) Total Score(Baseline (DB) to 12 Months of DB Phase)
- Number of Participants With Symptoms of Akathisia Assessed Using Barnes Akathisia Rating Scale (BARS) Score(Up to 12 Months of DB Phase)
- Change From Baseline in the Abnormal Involuntary Movement Scale (AIMS) Total Score(Baseline (DB) to 12 Months of DB Phase)
- Number of Participants Based on Columbia Suicide Severity Rating Scale (C-SSRS) Total Score(Baseline and endpoint (12 Months of DB Phase))
- Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Values During DB Phase(Baseline (DB) to 12 Months of DB Phase)
- Change From Baseline in the Body Mass Index (BMI) During DB Phase(Baseline (DB) to 12 Months of DB Phase)
- Change From Baseline in the Waist Circumference During DB Phase(Baseline (DB) to 12 Months of DB Phase)
- Change From Baseline in the Body Weight During DB Phase(Baseline (DB) to 12 Months of DB Phase)
- Change From Baseline in the Vital Signs (Pulse Rate) During DB Phase(Baseline (DB) to 12 Months of DB Phase)
- Change From Baseline in the Vital Signs (Systolic Blood Pressure [SBP] and Diastolic Blood Pressure [DBP]) During DB Phase(Baseline (DB) to 12 Months of DB Phase)
- Change From Baseline in Positive and Syndrome Scale (PANSS) Subscales Score During DB Phase(Baseline (DB) to 12 Months of DB Phase)
- Number of Participants With Treatment-emergent Clinically Significant Abnormal Laboratory Values in Chemistry During DB Phase(Up to 12 Months of DB Phase)
- Number of Participants With Treatment-emergent Clinically Significant Abnormal Laboratory Values in Hematology During DB Phase(Up to 12 Months of DB Phase)