Stephen B. Shrewsbury, Impel NeuroPharma, Inc, 201 Elliott Ave West, Ste 260, Seattle, WA 98119.
Impel NeuroPharma, Inc, Seattle, Washington, USA.
J Clin Psychiatry. 2020 Jun 30;81(4):19m13086. doi: 10.4088/JCP.19m13086.
INP105 is a drug-device combination of olanzapine and technology that delivers a powder formulation of olanzapine to the vascular-rich upper nasal space. This study evaluated the pharmacokinetics, pharmacodynamics, safety, and tolerability of single ascending doses of INP105, olanzapine intramuscular (OLZ IM), and olanzapine oral disintegrating tablet (OLZ ODT).
This was a phase 1, active and double-blind placebo comparator-controlled, ascending-dose, 2-period, incomplete-block, 1-way crossover study in 40 healthy subjects, randomized to single doses of OLZ IM (5 or 10 mg) or OLZ ODT (10 mg) in Period 1 and then 1 of 3 doses (5 mg, 10 mg, or 15 mg) of INP105 or placebo in Period 2 between July and October 2018. Sedation and attention were evaluated by visual analog scale (VAS), the Agitation/Calmness Evaluation Scale (ACES), and the Digit Symbol Substitution Test (DSST).
At equivalent doses, INP105 provided similar area under the drug concentration-time curve (AUC) from time 0 to the last measurable concentration, AUC from time 0 to infinity, and maximum observed concentration (Cmax) as OLZ IM and greater Cmax than but similar AUCs to OLZ ODT. Median time to maximum concentration was less for INP105 (15, 10, and 9.5 min for 5 mg, 10 mg, and 15 mg, respectively) than for OLZ IM (20 and 15 min for 5 mg and 10 mg, respectively) or OLZ ODT (120 min). Effects as measured with the VAS, ACES, and DSST with INP105 5 mg were comparable to those with OLZ IM 5 mg, with earlier onset for INP105 10 mg and 15 mg and greater effects than placebo and OLZ ODT. The incidence of treatment-emergent adverse events with INP105 5 mg, 10 mg, and 15 mg was 80%, 66.7%, and 75%, respectively, compared to 90% and 100% for OLZ IM 5 mg and 10 mg, respectively, and 83.3% for OLZ ODT; most common were dizziness, hypotension, and orthostatic symptoms.
INP105 has rapid absorption and pharmacodynamic effects and may represent an effective, convenient, noninvasive, and well-tolerated alternative for treating acutely agitated patients by self- or caregiver administration in the home, community, or hospital environments.
ClinicalTrials.gov identifier: NCT03624322.
INP105 是一种奥氮平和技术的药物-器械组合，可将奥氮平的粉末制剂递送至富含血管的鼻腔上部。本研究评估了 INP105、肌肉注射奥氮平（OLZ IM）和奥氮平口服分散片（OLZ ODT）单次递增剂量的药代动力学、药效学、安全性和耐受性。
这是一项在 40 名健康受试者中进行的、为期 1 期、主动、双盲、安慰剂对照、递增剂量、2 期、不完全块、1 期、交叉研究，受试者随机接受 OLZ IM（5 或 10 mg）或 OLZ ODT（10 mg）单次剂量，然后在 2018 年 7 月至 10 月期间进入第 2 期，接受 INP105 的 3 个剂量（5 mg、10 mg 或 15 mg）或安慰剂中的 1 种。镇静和注意力通过视觉模拟量表（VAS）、激动/平静评估量表（ACES）和数字符号替换测试（DSST）进行评估。
在等效剂量下，INP105 提供了与 OLZ IM 相似的药物浓度-时间曲线下面积（AUC）从 0 到最后可测量浓度、AUC 从 0 到无穷大、最大观察浓度（Cmax），且 Cmax 大于但 AUC 与 OLZ ODT 相似。INP105（5 mg、10 mg 和 15 mg 的中位达峰时间分别为 15、10 和 9.5 分钟）的达峰时间短于 OLZ IM（5 mg 和 10 mg 的分别为 20 和 15 分钟）或 OLZ ODT（120 分钟）。INP105 5 mg 的 VAS、ACES 和 DSST 测量的效应与 OLZ IM 5 mg 相当，INP105 10 mg 和 15 mg 的作用更早出现，且比安慰剂和 OLZ ODT 更强。INP105 5 mg、10 mg 和 15 mg 的治疗中出现的不良事件发生率分别为 80%、66.7%和 75%，而 OLZ IM 5 mg 和 10 mg 分别为 90%和 100%，OLZ ODT 为 83.3%；最常见的不良事件为头晕、低血压和直立性症状。
INP105 具有快速吸收和药效学作用，可能代表一种有效的、方便的、非侵入性的、耐受性良好的替代治疗方法，可通过自我或护理人员在家、社区或医院环境中对急性激越患者进行治疗。
ClinicalTrials.gov 标识符：NCT03624322。
