A Single-Dose, Open-Label, Randomized, Parallel-Group Study to Assess the Pharmacokinetics, Safety, and Tolerability of a Paliperidone Palmitate 3-Month Formulation in Subjects With Schizophrenia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 328
- 主要终点
- Plasma concentration of Paliperidone (Period 1)
研究概览
简要总结
The purpose of this study is to assess the pharmacokinetics, safety, and tolerability of a paliperidone palmitate 3-month formulation in patients with schizophrenia.
详细描述
This is a multicenter, randomized (the study drug is assigned by chance), open-label (all people know the identity of the intervention), parallel-group (each group of patients will be initiated simultaneously) study in 4 panels (A, B, C and D). Each panel will comprise 2 single-dose treatment periods. In Period 1, all patients from the 4 panels will receive an intramuscular (i.m.) injection with 1 mg paliperidone as an immediate release (IR) solution to assess tolerability and allergic or hypersensitivity reactions potentially related to paliperidone, and to establish the relative bioavailability (the extent to which a drug or other substance becomes available to the body) of paliperidone palmitate versus paliperidone IR. Patients in Panels A and C will receive an i.m. injection with 1 mg paliperidone IR solution in the gluteal muscle, and patients in Panel B and D will receive an i.m. injection with 1 mg paliperidone IR solution in the deltoid or gluteal muscle. Patients who tolerate this injection and have completed all assessments on Day 5 of Period 1 will be enrolled in Period 2. In Period 2, patients will receive a single dose of 3-month paliperidone palmitate i.m. injection at the dosages defined for each panel. The study drug injection will be followed by a 96-hour observation period in Period 1, and a 364-day or 544-day observation period in Period 2. Successive study drug administrations will be separated by a washout period (period when receiving no treatment) of at least 7 and no more than 21 days. The total study length for all patients is from 53 weeks to a maximum of 58 weeks. Patients in Panel B, if consented, and Panel D will participate in the extension period of approximately 26 weeks in order to obtain additional assessments to be able to characterize the pharmacokinetics (PK) profile. Pharmacokinetics explores how the drug is absorbed in the body, distributed within the body, and how it is removed from the body over time. Therefore, for those who participate in the extension period, the total study duration will be approximately 84 weeks.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with schizophrenia or schizoaffective disorder, for at least 1 year before screening
- •Clinically stable with no hospitalizations for schizophrenia exacerbation or change in current antipsychotic medications for 3 months prior to screening
- •Stabilized on antipsychotic medications other than risperidone, paliperidone, ziprasidone, clozapine, thioridazine, or any long acting injectable.
- •For panel D only, no detectable plasma concentration of risperidone or paliperidone > 0.1ng/mL at screening. A quantifiable and stable level of paliperidone not exceeding 0.25 ng/mL is allowed if such paliperidone value is explained by (documented) use of paliperidone palmitate (last dose administered > 12 months prior to baseline)
- •Has a total PANSS score of 70 or less at both screening and Day-1 (Period 1)
- •Woman is postmenopausal, surgically sterile, abstinent or, if sexually active, practices an effective method of birth control during participation in the study or for at least 6 months after the last dose of study drug, whichever is longer
- •Woman has negative pregnancy test at screening and on Day -1 of Period 1
- •Man agrees to use an adequate contraception method as deemed appropriate by the investigator and agrees to not donate sperm during participation in the study or for at least 6 months after the last dose of study drug, whichever is longer
- •Body Mass Index (BMI) between 17 and 35 kg/m2 (inclusive). Body weight of at least 50 kg for patients enrolled in panel A, B and C. For patients enrolled in panel D only: body weight of at least 47 kg
排除标准
- •Attempted suicide within 12 months before screening or is at imminent risk of suicide or violent behavior
- •Has diagnosis of alcohol or substance dependence, with the exception of nicotine or caffeine dependence, within 12 months prior to screening, or diagnosis of substance abuse within 3 months prior to screening
- •Has a positive drug screen test for barbiturates, cocaine, amphetamines or opiates, or has a positive alcohol screen test unless positive toxicology screen is explained by a prescribed allowed medication
- •Is in his/her first episode of psychosis
- •Has a history of or has a current clinically significant medical illness that the investigator considers should exclude the patients or that could interfere with the interpretation of the study results
- •Has clinically significant abnormal values at screening or at baseline for hematology, clinical chemistry or for urinalysis, as deemed appropriate by the investigator
- •Has a clinically relevant abnormality in the physical examination, vital signs or 12 lead electrocardiogram (ECG) at screening or at baseline as deemed appropriate by the investigator
- •Has a history or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval
- •Concomitant use of medications that the investigator considers should exclude the patients or that could interfere with the interpretation of the study results
- •Any other condition or circumstance that the investigator considers should exclude the patients or that could interfere with the interpretation of the study results
研究组 & 干预措施
Panel C
Panel C consists of 1 treatment group
干预措施: Paliperidone palmitate F016 (Drug)
Panel A
Panel A consists of 2 treatment groups
干预措施: Paliperidone IR (Period 1) (Drug)
Panel B
Panel B consists of 5 treatment groups
干预措施: Paliperidone IR (Period 1) (Drug)
Panel C
Panel C consists of 1 treatment group
干预措施: Paliperidone IR (Period 1) (Drug)
Panel D
Panel D consists of 4 treatment groups
干预措施: Paliperidone IR (Period 1) (Drug)
结局指标
主要结局
Plasma concentration of Paliperidone (Period 1)
时间窗: 14 time points over 96 hours
Plasma concentration of Paliperidone (Period 2)
时间窗: 29 time points over 544 days
次要结局
- The change from baseline in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) (Period 1)(Baseline and 96 hours)
- Changes in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) observed across multiple time points between baseline and 544 days (Period 2)(Baseline and 544 days)
- The change from baseline in Clinical Global Impression (CGI-S) (Period 1)(Baseline and 96 hours)
- Changes in Clinical Global Impression (CGI-S) observed across multiple time points between baseline and 544 days (Period 2)(Baseline and 544 days)
- Changes from Baseline in Abnormal Involuntary Movement Scale (AIMS) for the ratings of dyskinesia (Period 1)(Baseline and 96 hours)
- Changes in Abnormal Involuntary Movement Scale (AIMS) for the ratings of dyskinesia observed across multiple time points between baseline and 544 days (Period 2)(Baseline and 544 days)
- Changes from Baseline in Barnes Akathisia Rating Scale (BARS) for the ratings of akathisia (Period 1)(Baseline and 96 hours)
- Changes in Barnes Akathisia Rating Scale (BARS) for the ratings of akathisia observed across multiple time points between baseline and 544 days (Period 2)(Baseline and 544 days)
- Changes from Baseline in Simpson and Angus Rating Scale (SAS) for the ratings of general extrapyramidal symptoms (EPS) (Period 1)(Baseline and 96 hours)
- Changes in Simpson and Angus Rating Scale (SAS) for the ratings of general extrapyramidal symptoms (EPS) observed across multiple time points between baseline and 544 days (Period 2)(Baseline and 544 days)
- Changes from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) (Period 1)(Baseline and 96 hours)
- Changes in Columbia-Suicide Severity Rating Scale (C-SSRS) observed across multiple time points between baseline and 544 days (Period 2)(Baseline and 544 days)
- Evaluation of the Injection Site (Period 1)(96 hours)
- Evaluation of the Injection Site (Period 2)(Baseline through day 112)
- Incidence of Adverse Events as a Measure of Safety and Tolerability(Approximately 84 weeks)
- Number of patients with abnormal clinical laboratory tests(Approximately 84 weeks)
- Number of patients with abnormal findings in electrocardiogram, vital signs and physical examination(Approximately 84 weeks)