Abstract：
Background: Aripiprazole lauroxil (AL) 1064 mg every 2 months following initiation using the AL NanoCrystal Dispersion formulation (ALNCD) plus 30-mg oral aripiprazole was efficacious and well tolerated in a 25-week, randomized, double-blind phase 3 trial in adults with acute schizophrenia. This post hoc analysis further characterized the safety of AL 1064 mg administered every 2 months and that of active control paliperidone palmitate (PP) 156 mg monthly based on occurrence, timing, and severity of adverse events (AEs) associated with antipsychotic medications.
Methods: This study was conducted between November 2017 and March 2019. AL or PP was initiated during an inpatient stay of ≥ 2 weeks with transition to outpatient treatment thereafter. Rates of AEs of clinical interest, including injection site reactions (ISRs), motor AEs, sedation, hypotension, prolactin level increase, weight gain, and suicidal ideation/behavior, were summarized through weeks 4, 9, and 25 for each treatment.
Results: Of 200 patients who received ≥ 1 dose of study treatment, 99 (49.5%) completed the study (AL, 57%; PP, 43%). Mean (SD) baseline Positive and Negative Syndrome Scale total scores were 94.1 (9.04) and 94.6 (8.41) in the AL and PP treatment groups, respectively. AEs were reported by 69/99 (70%) patients administered AL and 72/101 (71%) administered PP; most AEs were mild or moderate in severity. ISRs (AL, 18.2%; PP, 26.7%) occurred primarily on days 1 and 8. All akathisia/restlessness AEs (AL, 10.1%; PP, 11.9%) occurred during the first 4 weeks; <10% of patients (either treatment) experienced hypotension, sedation, or suicidal ideation/behavior events. Weight gain of ≥ 7% from baseline occurred in 9.3% of AL- and 23.8% of PP-treated patients. Median prolactin concentrations changed by -4.60 and -3.55 ng/mL among AL-treated males and females, respectively, and did not exceed 2 times normal levels in any AL-treated patients. In PP-treated patients, changes were 21.20 and 80.40 ng/mL and concentrations exceeded 2 times normal in 38% and 88% of males and females, respectively.
Conclusions: No new early- or late-emerging safety concerns were observed through 25 weeks of treatment with AL 1064 mg every 2 months following initiation using ALNCD plus 30-mg oral aripiprazole. Results were consistent with known safety profiles of AL and PP and support the safety of AL 1064 mg every 2 months initiated using ALNCD plus 30-mg oral aripiprazole.
Trial Registration: ClinicalTrials.gov identifier: NCT03345979.
Methods: This study was conducted between November 2017 and March 2019. AL or PP was initiated during an inpatient stay of ≥ 2 weeks with transition to outpatient treatment thereafter. Rates of AEs of clinical interest, including injection site reactions (ISRs), motor AEs, sedation, hypotension, prolactin level increase, weight gain, and suicidal ideation/behavior, were summarized through weeks 4, 9, and 25 for each treatment.
Results: Of 200 patients who received ≥ 1 dose of study treatment, 99 (49.5%) completed the study (AL, 57%; PP, 43%). Mean (SD) baseline Positive and Negative Syndrome Scale total scores were 94.1 (9.04) and 94.6 (8.41) in the AL and PP treatment groups, respectively. AEs were reported by 69/99 (70%) patients administered AL and 72/101 (71%) administered PP; most AEs were mild or moderate in severity. ISRs (AL, 18.2%; PP, 26.7%) occurred primarily on days 1 and 8. All akathisia/restlessness AEs (AL, 10.1%; PP, 11.9%) occurred during the first 4 weeks; <10% of patients (either treatment) experienced hypotension, sedation, or suicidal ideation/behavior events. Weight gain of ≥ 7% from baseline occurred in 9.3% of AL- and 23.8% of PP-treated patients. Median prolactin concentrations changed by -4.60 and -3.55 ng/mL among AL-treated males and females, respectively, and did not exceed 2 times normal levels in any AL-treated patients. In PP-treated patients, changes were 21.20 and 80.40 ng/mL and concentrations exceeded 2 times normal in 38% and 88% of males and females, respectively.
Conclusions: No new early- or late-emerging safety concerns were observed through 25 weeks of treatment with AL 1064 mg every 2 months following initiation using ALNCD plus 30-mg oral aripiprazole. Results were consistent with known safety profiles of AL and PP and support the safety of AL 1064 mg every 2 months initiated using ALNCD plus 30-mg oral aripiprazole.
Trial Registration: ClinicalTrials.gov identifier: NCT03345979.
摘要：
背景：在开始使用AL纳米晶体分散制剂（ALNCD）加30毫克口服阿立哌唑后，每2个月一次的阿立哌唑（AL）1064毫克，在25周内有效且耐受性良好，随机化，成人急性精神分裂症患者的双盲3期试验。该事后分析进一步表征了每2个月施用的AL1064mg和基于发生率每月156mg的活性对照棕榈酸帕潘立酮（PP）的安全性。定时,以及与抗精神病药物相关的不良事件（AE）的严重程度。
方法：本研究于2017年11月至2019年3月进行。在住院≥2周期间开始AL或PP，此后过渡到门诊治疗。临床感兴趣的AE率，包括注射部位反应（ISR），电机AE，镇静,低血压,催乳素水平升高,体重增加,和自杀意念/行为，总结了每个治疗的第4、9和25周。
结果：在200名接受≥1剂量研究治疗的患者中，99（49.5%）完成了研究（AL，57%；PP，43%）。AL和PP治疗组的平均（SD）基线阳性和阴性综合征量表总分分别为94.1（9.04）和94.6（8.41），分别。69/99（70％）接受AL和72/101（71％）接受PP的患者报告了AE；大多数AE的严重程度为轻度或中度。ISR(AL,18.2%;PP,26.7%)主要发生在第1天和第8天。所有静坐不能/躁动不良事件（AL，10.1%;PP,11.9％）在前4周内发生；<10％的患者（任一治疗）经历低血压，镇静,或自杀意念/行为事件。与基线相比体重增加≥7%发生在9.3%的AL和23.8%的PP治疗患者中。在接受AL治疗的男性和女性中，催乳素浓度中位数变化为-4.60和-3.55ng/mL，分别,并且在任何接受AL治疗的患者中都不超过正常水平的2倍。在PP治疗的患者中，变化分别为21.20和80.40ng/mL，38%和88%的男性和女性浓度超过正常值的2倍，分别。
结论：在开始使用ALNCD加30mg口服阿立哌唑后，每2个月使用AL1064mg治疗25周，未观察到新的早期或晚期出现的安全性问题。结果与已知的AL和PP的安全性特征一致，并且支持每2个月使用ALNCD和30mg口服阿立哌唑开始的AL1064mg的安全性。
试验注册：ClinicalTrials.gov标识符：NCT03345979。
方法：本研究于2017年11月至2019年3月进行。在住院≥2周期间开始AL或PP，此后过渡到门诊治疗。临床感兴趣的AE率，包括注射部位反应（ISR），电机AE，镇静,低血压,催乳素水平升高,体重增加,和自杀意念/行为，总结了每个治疗的第4、9和25周。
结果：在200名接受≥1剂量研究治疗的患者中，99（49.5%）完成了研究（AL，57%；PP，43%）。AL和PP治疗组的平均（SD）基线阳性和阴性综合征量表总分分别为94.1（9.04）和94.6（8.41），分别。69/99（70％）接受AL和72/101（71％）接受PP的患者报告了AE；大多数AE的严重程度为轻度或中度。ISR(AL,18.2%;PP,26.7%)主要发生在第1天和第8天。所有静坐不能/躁动不良事件（AL，10.1%;PP,11.9％）在前4周内发生；<10％的患者（任一治疗）经历低血压，镇静,或自杀意念/行为事件。与基线相比体重增加≥7%发生在9.3%的AL和23.8%的PP治疗患者中。在接受AL治疗的男性和女性中，催乳素浓度中位数变化为-4.60和-3.55ng/mL，分别,并且在任何接受AL治疗的患者中都不超过正常水平的2倍。在PP治疗的患者中，变化分别为21.20和80.40ng/mL，38%和88%的男性和女性浓度超过正常值的2倍，分别。
结论：在开始使用ALNCD加30mg口服阿立哌唑后，每2个月使用AL1064mg治疗25周，未观察到新的早期或晚期出现的安全性问题。结果与已知的AL和PP的安全性特征一致，并且支持每2个月使用ALNCD和30mg口服阿立哌唑开始的AL1064mg的安全性。
试验注册：ClinicalTrials.gov标识符：NCT03345979。
