Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
A Phase 1, Open-Label, Two-Sequence, Five-Period, Single Ascending Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasal Olanzapine and Relative Bioavailability Compared to Olanzapine Intramuscular Injection in Healthy Adult Participants
This is a Phase 1, open-label, 5-period, 2-sequence, single ascending dose study designed to assess the pharmacokinetics, dose proportionality, safety, and tolerability of NRL-1004 (olanzapine nasal spray), and to assess the relative bioavailability of NRL-1004, compared to olanzapine intramuscular injection (ZYPREXA IM), in healthy adult participants. The study will be conducted in a single clinical research unit (CRU).
研究概览
地位
条件
研究类型
注册 (估计的)
阶段
- 阶段1
联系人和位置
学习联系方式
- 姓名:Stella Ngo, PhD
- 电话号码:(908) 499-2326
- 邮箱:sngo@neurelis.com
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
-
A participant will be eligible for study participation if the participant meets all of the following criteria:
-
Male and female participants aged between 18 to 65 years, inclusive.
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Body weight ≥50 kg and body mass index (BMI) within the range of 18.0 to 30.0 kg/m2 (inclusive).
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Participants must be healthy and without clinically significant abnormalities as assessed at screening and at first CRU admission visit.
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No clinically significant abnormality on 12-lead ECG.
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Normal blood pressures and pulse rate at screening and at first CRU admission visit.
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If male, meets one of the following criteria:
- Is able to procreate and agrees to use one of the accepted contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last drug administration.
- Is unable to procreate; defined as surgically sterile
-
If female, meets one of the following criteria:
- Is of childbearing potential and agrees to use an acceptable contraceptive method.
- Is of non-childbearing potential, defined as surgically sterile or is in a postmenopausal state.
-
Exclusion Criteria:
-
A participant will be excluded from the study if the participant meets any of the following criteria:
- Female who is pregnant or plans to become pregnant, or who is lactating or plans to be lactating during the study.
- Clinically significant cardiac, cardio- or cerebrovascular, respiratory, gastrointestinal, endocrine, hematologic, psychiatric, renal, hepatic, pulmonary, immunologic, dermatologic or nervous system disorders.
- History of or current postural orthostatic tachycardia syndrome, or orthostatic hypotension at screening and at first CRU admission.
- Current or history of psychiatric or psychotic diagnosis.
- Evidence or history of suicidal ideation as per the C-SSRS administered at screening and at first CRU admission, violence, or homicidality.
- Major surgery or open biopsy within 90 days prior to screening or expected/scheduled to have such procedure(s) performed during the study.
- Any other conditions or unstable diseases/disorders which may affect the ability of the participant to comply with the protocol requirements, jeopardize the safety of the participant, or impact the interpretation of the study results.
- Any clinical or laboratory measurements assessed by the Investigator as clinically relevant.
- Positive blood screen for human immunodeficiency virus (HIV-1/2), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCV Ab) at screening.
- History of drug abuse or alcohol abuse within 12 months prior to Screening, and/or unwilling to refrain from such use throughout the study.
- History of smoking or use of tobacco or other nicotine-containing products within 3 months prior to screening and unwilling to refrain throughout the study.
- Use of medical or recreational cannabinoid use and unwilling to refrain throughout the study.
- Positive drug screen for alcohol, cotinine, or illicit drug/substance of abuse.
- Presence of acute conditions that could interfere with IN administration and drug absorption.
- National Institute of Health (NIH) Toolbox Odor Identification test score of 0 at screening.
- Current use of any drugs that may affect the absorption, metabolism, or elimination of study drugs, and that such treatment cannot be discontinued at least 4 weeks prior to screening and throughout the study.
- Unwilling to refrain from intake of food or consumption of caffeine-containing drinks that affect CYP1A2 activity throughout the course of the study.
- Use of any prescription medication within 14 days or 5 half-lives prior to the first dose of study drug or during the study unless approved by the Investigator. (Hormonal contraceptives or hormone replacement therapy are allowed.)
- Use of any over-the-counter medications within 14 days or 5 half lives prior to Screening and throughout the study unless approved by the Investigator.
- History of hypersensitivity or anaphylactic reactions to the active ingredient or any excipients of study drugs.
- Received an investigational drug within 30 days or within 5 half-lives or twice the duration of the biological effect of the investigational drug in previous study prior to screening.
- Inadequate or difficult venous access.
- Donation of plasma in the 7 days prior to the first study drug administration, or donation of 500 mL or more of blood in the 56 days prior to the first study drug administration.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:顺序分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的:NRL 1004 25 mg/mL solution
NRL-1004 (olanzapine nasal spray), 25 mg/mL solution |
Olanzapine nasal spray |
|
实验性的:NRL-1004 50 mg/mL solution
NRL-1004 (olanzapine nasal spray), 50 mg/mL solution |
Olanzapine nasal spray |
|
实验性的:NRL-1004 75 mg/mL solution
NRL-1004 (olanzapine nasal spray), 75 mg/mL solution |
Olanzapine nasal spray |
|
实验性的:NRL-1004 100 mg/mL solution
NRL-1004 (olanzapine nasal spray), 100 mg/mL solution |
Olanzapine nasal spray |
|
有源比较器:ZYPREXA IM 10mg/vial
ZYPREXA IntraMuscular (olanzapine) Injection, Powder, for Solution for Intramuscular use, 10 mg/vial |
Olanzapine IM injection |
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Pharmacokinetic parameters of olanzapine in plasma
大体时间:Time zero to 14 days postdose
|
Maximum observed plasma concentration (Cmax) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
大体时间:Time zero to 14 days postdose
|
Time to maximum plasma concentration (Tmax) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
大体时间:Time zero to 14 days postdose
|
Area under the plasma concentration time curve (AUC) from time zero to the last quantifiable concentration (AUC0-t) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
大体时间:Time zero to 14 days postdose
|
AUC from time zero extrapolated to infinity (AUC0-inf) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
大体时间:Time zero to 14 days postdose
|
Partial AUC from time zero to 2 hours postdose (AUC0-2 h) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
大体时间:Time zero to 14 days postdose
|
Partial AUC from time zero to 24 hours postdose (AUC0-24 h) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
大体时间:Time zero to 14 days postdose
|
Terminal phase half-life (t½) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
大体时间:Time zero to 14 days postdose
|
Terminal phase rate constant (λz) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
大体时间:Time zero to 14 days postdose
|
Apparent clearance (CL/F) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
大体时间:Time zero to 14 days postdose
|
Apparent volume of distribution (Vz/F) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
大体时间:Time zero to 14 days postdose
|
Relative bioavailability (Frel) |
Time zero to 14 days postdose
|
合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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