Phase1 Randomized, Double-Blind, Placebo/Active-Controlled, SAD, 2-Way, Incomplete Block, 2-Period Crossover, Safety, Tolerability, PK/PD Study of 3 Doses INP105 (Olanzapine Delivered by I231 POD® Device) Nasal Spray in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- PK profile of OLZ INP105 Cmax
研究概览
简要总结
The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of INP105, which is an investigational drug-device combination product comprised of the drug component OLZ administered by a Precision Olfactory Delivery (POD®) nasal spray device (I231 POD® Device). The proposed indication for INP105 is the treatment of acute agitation associated with schizophrenia and bipolar I disorder.
详细描述
This is a randomized, double-blind, placebo- and active-controlled, ascending-dose, 2-way, 2- period, incomplete block, crossover, Phase 1 trial to compare the safety, tolerability, PK and PD of 3 single doses of INP105 with the safety, tolerability, PK and PD of 1 dose of Zyprexa IM (5 mg) and 1 dose of oral Zyprexa Zydis (10 mg). Randomization for Periods 1 and 2 will occur for each subject on Day 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind, placebo-controlled
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult male (N=at least 9) and female (N=at least 9) 18 to 55 years of age (inclusive) at Screening, in good general health, with no significant medical history and no clinically significant abnormalities on physical examination at Screening or before first dose of IP.
- •Subjects must have a Body Mass Index (BMI) between 18 and 32 kg/m2 inclusive.
- •Negative urine drug screen/alcohol breath test at Screening and Day -
- •Repeat tests may be performed if false positive results are suspected.
- •Subjects must have the ability and willingness to attend the necessary visits at the study centre.
- •Written informed consent signed prior to entry into the study.
- •Female subjects of childbearing potential, and male subjects and their partners, must agree to use adequate contraception, defined as complete abstinence, documented evidence of surgical sterilization or condom plus approved contraceptive method
排除标准
- •Known hypersensitivity to Zyprexa IM, Zyprexa Zydis or any of the ingredients in them or in INP105 or the placebo.
- •Recently (within 3 months) or currently taking Zyprexa (any formulation).
- •Subjects taking medications known to inhibit or induce CYP1A2 at any time during the study period, and any subjects taking prescription medications, over the counter medications or supplements that, in the opinion of the Investigator, may impact the subject's response to INP105 or impact the subject's participation in the study. Oral contraceptives are permitted.
- •Subjects with medical history of hypotension or currently taking anti-hypertensives at Screening or throughout the study.
- •Current or recent smokers (<3 months since quitting); inadvertent one-off smokers and social smokers will also be excluded.
- •Females who are pregnant or lactating.
- •Subjects with any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the subject will comply with the study.
- •Abnormal and clinically significant laboratory test results.
- •History or presence of alcohol or drug abuse within the 2 years prior to the first IP administration.
- •Blood donation or significant blood loss within 60 days prior to the first IP administration.
- •Plasma donation within 7 days prior to the first IP administration.
- •Administration of IP in another trial within 30 days or 5 half-lives (whichever is longer) prior to the first IP administration.
- •Significant surgery within the past 3 months prior to the first IP administration determined by the Investigator to be clinically relevant.
- •Failure to satisfy the Investigator of fitness to participate for any other reason.
- •Acute illness within 30 days prior to Day
- •Subjects with minor viral illnesses (for example, upper respiratory tract infection) within 30 days prior to Day 1 may be randomized if all symptoms are resolved by admission and at the discretion of the Investigator.
- •Any nasal congestion, deviated septum, or physical blockage in either nostril.
- •Positive for human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C
研究组 & 干预措施
Period 1
Period 1 (n=36) assignment to 1 of 2 reference therapy treatment groups (Zyprexa 5mg IM or Zydis 10mg orally disintegrating wafer, 10mg) over 3 cohorts (single dose)
干预措施: Zyprexa IM (Drug)
Period 1
Period 1 (n=36) assignment to 1 of 2 reference therapy treatment groups (Zyprexa 5mg IM or Zydis 10mg orally disintegrating wafer, 10mg) over 3 cohorts (single dose)
干预措施: Zydis (Drug)
Period 2
Period 2 (n=36) assignment to 1 of 3 IP treatment groups (INP105 of 5, 10, or 20mg or placebo) administered with the I231 POD® Device) over 3 cohorts (single dose)
干预措施: INP105 (Drug)
Period 2
Period 2 (n=36) assignment to 1 of 3 IP treatment groups (INP105 of 5, 10, or 20mg or placebo) administered with the I231 POD® Device) over 3 cohorts (single dose)
干预措施: I231 POD® Device (Device)
结局指标
主要结局
PK profile of OLZ INP105 Cmax
时间窗: 72 hours
Cmax
PK profile of Zyprexa IM Tmax
时间窗: 72 hours
Tmax
Safety and tolerability
时间窗: 30 days
AEs and SAEs as assessed from baseline by physical exam, ECG, vital signs, and clinical laboratory results
PK profile of OLZ INP105 Tmax
时间窗: 72 hours
Tmax
PK profile of Zyprexa IM Cmax
时间窗: 72 hrs
Cmax
PK profile of Zyprexa Zydis Tmax
时间窗: 72 hours
Tmax
PD effects of INP105 vs placebo
时间窗: 72 hours
Changes in motor function measured by PD assessment compared to overall PK profile following ascending doses of INP105
PK profile of Zyprexa Zydis Cmax
时间窗: 72 hours
Cmax
PD effects of Zyprexa IM
时间窗: 72 hours
Changes in motor function measured by PD assessment compared to overall PK profile following a single dose of 5mg of Zyprexa IM
PD effects of Zyprexa Zydis
时间窗: 72 hours
Changes in motor function measured by PD assessment compared to overall PK profile following a single 10mg dose of Zyprexa Zydis oral disintegrating wafer
次要结局
未报告次要终点