An Open-label Parallel Arm Multiple Dose Tolerability, Pharmacokinetics and Safety Study in Adult Patients With Schizophrenia Following Administration of Aripiprazole IM Depot Formulation Once Every Four Weeks
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events as a Measure of Safety
研究概览
简要总结
This study will evaluate the safety, tolerability, efficacy and pharmacokinetics of aripiprazole intramuscular (IM) depot multiple doses every 4 weeks in adult patients with schizophrenia.
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 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria
- •good physical health as determined by normal medical history, clinical laboratory results, electrocardiograms (ECGs) and physical examinations
- •ability to provide informed consent and/or consent from a legally acceptable representation
- •body mass index (BMI) of 18 to 35 kg/m^2
排除标准
- •sexually active males and females of child-bearing potential who are not practicing double barrier birth control or are not abstinent during the study plus 30 days for female or 90 days for males following the last dose of medication
- •history of drug or alcohol abuse within 6 months and/or positive urine drug screen
- •participants who consume alcohol beverages routinely
- •participants who consume alcohol beverages during the screening period
- •use of any antipsychotic medication, other prohibited psychotropic medication, and any cytochrome P450 2D6 (CYP2D6) and cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 inducers within 14 days
- •use of any prescription medication unless approved by Medical Monitor or Study Director
- •history of current hepatitis or carrier of HBsAg (Hepatitis B surface antigen) and/or Hepatitis C Virus antibodies (anti-HCV)
- •females who are pregnant or lactating
- •participants who have participated in any clinical trial involving a psychotropic medication within one month prior to enrollment; participants who have participated in a previous IM Depot study within the last 1 year; patients who have previously enrolled and received study medication in an aripiprazole IM Depot clinical trial
- •donation of blood or plasma to a blood bank or in a clinical study (except a screening visit)within 30 days prior to enrollment
- •any major surgery within 30 days prior to enrollment
- •blood transfusion within 30 days prior to enrollment
- •evidence of organ dysfunction or any clinically significant deviation from normal in the physical, electrocardiographic, or clinical laboratory examinations
- •patient represents a significant risk of committing suicide based on history
- •patients currently in an acute relapse
- •patients with Axis I (DSM-IV) diagnosis of schizoaffective or bipolar disorder
- •patients who are considered treatment-resistant to antipsychotic medication
- •patients with a history of neuroleptic malignant syndrome
- •any other sound medical reason as determined by the clinical investigator
研究组 & 干预措施
400 mg Aripiprazole IM Depot
400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
干预措施: aripiprazole IM depot (Drug)
400 mg Aripiprazole IM Depot
400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
干预措施: aripiprazole tablets (Drug)
300 mg Aripiprazole IM Depot
300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
干预措施: aripiprazole IM depot (Drug)
300 mg Aripiprazole IM Depot
300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
干预措施: aripiprazole tablets (Drug)
200 mg Aripiprazole IM depot
200 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
干预措施: aripiprazole IM depot (Drug)
200 mg Aripiprazole IM depot
200 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
干预措施: aripiprazole tablets (Drug)
结局指标
主要结局
Number of Participants With Adverse Events as a Measure of Safety
时间窗: 7 Months
Safety and tolerability was assessed by the number of participants with adverse events (AE). An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a subject while enrolled in the study, whether or not it was considered drug-related by the investigator. Abnormal laboratory test findings were considered AEs if, in the opinion of the investigator, they represented an abnormal (ie, clinically significant) change from baseline for that individual participant.
Aripiprazole Maximum Steady State Plasma Concentration (Css,Max)
时间窗: Pre-dose and 1 to 1344 hours post-dose at Month 5
Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,max were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.
Aripiprazole Minimum Steady State Plasma Concentration (Css,Min)
时间窗: 672 hours post-dose at Month 5
Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,min were determined directly from the observed data at 672 hours after the fifth monthly injection.
Aripiprazole Area Under the Concentration-time Curve at Steady-state (AUCτ)
时间窗: Pre-dose and 1 to 1344 hours post-dose at Month 5
Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values of AUCτ were estimated using the linear trapezoidal rule during each dosing interval from 0 to 1344 hours post-dose.
次要结局
- Aripiprazole Maximum (Peak) Plasma Concentration (Tmax)(Pre-dose and 1 to 1344 hours post-dose at Month 5)
- Aripiprazole Steady-state Plasma Concentration (Css,Avg)(Pre-dose and 1 to 1344 hours post-dose at Month 5)
- Aripiprazole Terminal-phase Elimination Half-life (t1/2,z)(Pre-dose and 1 to 1344 hours post-dose at Month 5)
- Dehydro-aripiprazole Maximum Steady State Plasma Concentration (Css,Max)(Pre-dose and 1 to 1344 hours post-dose at Month 5)
- Dehydro-aripiprazole Minimum Steady State Plasma Concentration (Css,Min)(Pre-dose and 1 to 1344 hours post-dose at Month 5)
- Dehydro-aripiprazole Area Under the Concentration-Time Curve at Steady-State (AUCτ)(Pre-dose and 1 to 1344 hours post-dose at Month 5)
- Dehydro-aripiprazole Maximum (Peak) Plasma Concentration (Tmax)(Pre-dose and 1 to 1344 hours post-dose at Month 5)
- Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 and Week 24(Baseline, Week 12, Week 24)
- Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Positive Subscale Scores at Week 12 and Week 24(Baseline, Week 12, Week 24)
- Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Negative Subscale Scores at Week 12 and Week 24(Baseline, Week 12, Week 24)
- Change From Baseline in the Clinical Global Impression- Severity of Illness Score (CGI-S) at Week 12 and Week 24(Baseline, Week 12, Week 24)
- Clinical Global Impression-Improvement Scale (CGI-I) at Week 12 and Week 24(Baseline, Week 12, Week 24)
- Number of Participants Hospitalized for Adverse Event "Worsening Schizophrenia"(7 Months)