An Open-label, Single- and Multiple-dose, Pharmacokinetic, Safety, and Tolerability Trial of Aripiprazole Long-acting Injectable Administered in the Deltoid or Gluteal Muscle in Adult Subjects With Schizophrenia or Bipolar I Disorder
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 4
- 主要终点
- Part A - Single Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole
研究概览
简要总结
The primary objective of this trial is to evaluate the pharmacokinetics (PK) of aripiprazole long-acting injectable (LAI) (420 mg) following deltoid or gluteal muscle administration in adult subjects with schizophrenia or bipolar I disorder.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Male and female subjects between 18 and 64 years of age, inclusive.
- •Body mass index of 18 to 35 kg/m2, inclusive.
- •A current diagnosis of schizophrenia or a current diagnosis of bipolar I disorder as defined by DSM-5 criteria.
- •Prior history of tolerating aripiprazole per investigator's judgment.
排除标准
- •Subjects who have met DSM-5 criteria for substance dependence within the past 180 days
- •Use of any psychotropic medications other than their current non-aripiprazole antipsychotic or mood stabilizer(s) medication or subjects who use more than one antipsychotic or mood stabilizer(s) medication at screening.
- •Subjects may not receive varenicline beyond screening.
- •Use of any prescription medication not specifically approved by the medical monitor.
- •Females who are pregnant or lactating. A negative serum pregnancy test must be confirmed prior to the first dose of IMP for all female subjects.
- •Subjects who had participated in any clinical trial involving a psychotropic medication within 1 month prior to enrollment; subjects who had participated in a previous aripiprazole LAI trial within the last 1 year (ie, enrolled but did not receive aripiprazole LAI); or who had previously enrolled and received IMP in an aripiprazole LAI clinical trial.
- •Any major surgery within 30 days prior to enrollment or scheduled/elective surgery during the trial.
- •Subjects currently in an acute relapse of schizophrenia.
- •Subjects with a current DSM-5 diagnosis other than schizophrenia or bipolar I disorder
- •Electroconvulsive therapy must not be conducted within 2 months prior to administration of the IMP
- •Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia as assessed by the investigator.
- •History of or current hepatitis or acquired immunodeficiency syndrome or carriers of HBsAg, anti-HCV, and/or HIV antibodies.
- •History of any significant drug allergy or known or suspected hypersensitivity, in particular to aripiprazole or other quinolinones.
- •Subjects deemed intolerant of receiving injections.
研究组 & 干预措施
Part A - Deltoid Site: Single Dose Group
Participants will receive a single dose of aripiprazole LAI.
干预措施: Aripiprazole (Drug)
Part A - Gluteal Site: Single Dose Group
Participants will receive a single dose of aripiprazole LAI.
干预措施: Aripiprazole (Drug)
Part A - Deltoid Site: Multiple Dose Group
Participants will receive five injections of aripiprazole LAI, administered at monthly intervals.
干预措施: Aripiprazole (Drug)
Part A - Gluteal Site: Multiple Dose Group
Participants will receive five injections of aripiprazole LAI, administered at monthly intervals.
干预措施: Aripiprazole (Drug)
Part B - Gluteal Site: Group 1 (X)
Participants will receive a single dose of aripiprazole LAI.
干预措施: Aripiprazole (Drug)
Part B - Gluteal Site: Group 1 (Y)
Participants will receive a single dose of aripiprazole LAI.
干预措施: Aripiprazole (Drug)
Part B - Gluteal Site: Group 2
Participants will receive a single dose of aripiprazole LAI.
干预措施: Aripiprazole (Drug)
结局指标
主要结局
Part A - Single Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 126
Part B - Group 1: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 57
Part B - Group 2: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 57
Part A - Single Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 28
Part B - Group 1: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 28
Part B - Group 2: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 28
Part A - Single Dose Group: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 126
Part B - Group 1: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 57
Part B - Group 2: Time to Reach the Maximum Plasma Concentration (Tmax) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 57
Part A - Single Dose Group: Area Under the Concentration-Time Curve from time Zero to Time t (the Last Observable Concentration; AUCt) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 126
Part B - Group 1: Area Under the Concentration-Time Curve from time Zero to Time t (the Last Observable Concentration; AUCt) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 57
Part B - Group 2: Area Under the Concentration-Time Curve from time Zero to Time t (the Last Observable Concentration; AUCt) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 57
Part A - Single Dose Group: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 28
Part B - Group 1: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 28
Part B - Group 2: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 28
Part A - Single Dose Group: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 126
Part B - Group 1: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 57
Part B - Group 2: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Aripiprazole (AUC∞) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 57
Part A - Single Dose Group: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 126
Part B - Group 1: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 57
Part B - Group 2: Terminal Phase Elimination Half-life (T1/2) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 1 to Day 57
Part A - Single Dose Group: Oral Clearance (CL/F) for Aripiprazole Only
时间窗: Day 1 to Day 126
Apparent clearance of the drug from plasma after extravascular administration (CL/F).
Part B - Group 1: Oral Clearance (CL/F) for Aripiprazole Only
时间窗: Day 1 to Day 57
Apparent clearance of the drug from plasma after extravascular administration (CL/F).
Part B - Group 2: Oral Clearance (CL/F) for Aripiprazole Only
时间窗: Day 1 to Day 57
Apparent clearance of the drug from plasma after extravascular administration (CL/F).
Part A - Multiple Dose Group: Maximum Observed Plasma Concentration (Cmax) for Aripiprazole and Dehydro-Aripiprazole (Following the Fifth Dose Only)
时间窗: Day 113 to Day 169
Fifth dose will be administered on Day 113.
Part A - Multiple Dose Group: Plasma Concentration at 28 Days Postdose (C28) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 29, Day 57, Day 84, Day 113, Day 141 (All post-dose)
Part A - Multiple Dose Group: Time to Reach the Maximum Plasma Concentration (Tmax) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 113 to Day 169
Participants will receive their 5th dose on Day 113.
Part A - Multiple Dose Group: Area Under the Concentration-Time Curve from Time Zero to 28 Days Postdose (AUC0-28) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 113 to Day 169
Participants will receive their 5th dose on Day 113.
Part A - Multiple Dose Group: Terminal Phase Elimination Half-life (T1/2) (Following the Fifth Dose Only) for Aripiprazole and Dehydro-Aripiprazole
时间窗: Day 113 to Day 169
Participants will receive their 5th dose on Day 113.
Part A - Multiple Dose Group: Oral Clearance (CL/F) (Following the Fifth Dose Only; for Aripiprazole Only)
时间窗: Day 113 to Day 169
Participants will receive their 5th dose on Day 113.
Part A - Multiple Dose Group: Ratio of Dehydro-Aripiprazole to Aripiprazole C28 and AUC0-28 (Following the Fifth Dose Only)
时间窗: Day 113 (following fifth dose) to Day 141
Participants will receive their 5th dose on Day 113.
次要结局
- Part A - Single Dose: Number of Participants with an Adverse Event (AE)(Day 1 to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Number of Participants with an Adverse Event (AE)(Day 1 to End of Trial (Maximum 169 Days from First Dose))
- Part B: Number of Participants with an Adverse Event (AE)(Day 1 to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Number of Participants with Markedly Abnormal Vital Sign Measurements(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Number of Participants with Markedly Abnormal Vital Sign Measurements(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Number of Participants with Markedly Abnormal Vital Sign Measurements(Baseline to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Number of Participants with Markedly Abnormal Electrocardiograms (ECGs) Results(Baseline to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Number of Participants with Markedly Abnormal Clinical Laboratory Results(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Number of Participants with Markedly Abnormal Clinical Laboratory Results(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Number of Participants with Markedly Abnormal Clinical Laboratory Results(Baseline to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Change from Baseline in Serum Prolactin(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Change from Baseline in Serum Prolactin(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Change from Baseline in Serum Prolactin(Baseline to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Number of Participants with Markedly Abnormal Physical Examination Results(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Number of Participants with Markedly Abnormal Physical Examination Results(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Number of Participants with Markedly Abnormal Physical Examination Results(Baseline to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception(Day 1 immediately post-dose, 1 hour post-dose (+/- 15 minutes), Day 14 and Day 29)
- Part A - Multiple Dose: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception(1-hour post-dose Day 1, Day 29, Day 57, Day 85, Day 113)
- Part B: Visual Analog Scale (VAS) Scores for Injection Site Pain Perception(Day 1 immediately post-dose, 1 hour post-dose (+/- 15 minutes), Day 14 and Day 29)
- Part A - Single Dose: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Change from Baseline of Columbia-Suicide Severity Rating Scale (C-SSRS) Score(Baseline to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Number of Injection Site Related Adverse Events(End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Number of Injection Site Related Adverse Events(End of Trial (Maximum 169 Days from First Dose))
- Part B: Number of Injection Site Related Adverse Events(End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)(Day 1 (predose) to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)(Day 1 (predose) to End of Trial (Maximum 169 Days from First Dose))
- Part B: Change from Baseline in Assessment of Extrapyramidal Symptoms (EPS)(Day 1 (predose) to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Change from Baseline in Positive and Negative Syndrome Scale Rating Criteria (PANSS) Score(Baseline to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score(Baseline to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWN-S) Score(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWN-S) Score(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Change from Baseline in Subjective Well-being under Neuroleptic Treatment-Short Form (SWNS) Score(Baseline to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score(Baseline to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Change from Baseline in Young Mania Rating Scale (YMRS) Score(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Change from Baseline in Young Mania Rating Scale (YMRS) Score(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Change from Baseline in Young Mania Rating Scale (YMRS) Score(Baseline to End of Trial (Maximum 57 Days from First Dose))
- Part A - Single Dose: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score(Baseline to End of Trial (Maximum 126 Days from First Dose))
- Part A - Multiple Dose: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score(Baseline to End of Trial (Maximum 169 Days from First Dose))
- Part B: Change from Baseline in Clinical Global Impression-Bipolar Version (CGI-BP) Score(Baseline to End of Trial (Maximum 57 Days from First Dose))