Comparative Randomized, Single Dose, Three-Arm, Parallel Open-Label Study to Characterize the Pharmacokinetics of 7.5 Mg Olanzapine Intranasal Spray and 7.5 Mg Olanzapine Intramuscular Injection After Administration to Healthy Male Adults Under Fasting Conditions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- (1) Bioavailability of test products compared to reference product based on pharmacokinetic parameter of AUC from time 0 to time t
研究概览
简要总结
NRL-4, a nasal spray formulation of the atypical antipsychotic olanzapine is being developed by Neurelis Inc. for use as a rescue medication for acute episodes of agitation in schizophrenia, schizoaffective and bipolar I disorder. Also being tested are different concentrations of Intravail A3. Intravail A3 belongs to a class of nonionic surfactants known as alkylglycosides. Alkylglycosides have been extensively studied for their ability to promote increased bioavailability of drugs via the nasal, oral, and ocular routes.
In this study it will be tested if the olanzapine in the two Test products will show comparable pharmacokinetics, safety and tolerability in comparison to the Reference product through the primary pharmacokinetic parameters Cmax, AUC from time 0 to time t and AUC from time 0 to infinity, and safety assessments, including nasal irritation, sedation and pain scales.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects aged 18 to 55 years, inclusive.
- •Body weight ≥51 kg and ≤111 kg, and body mass index (BMI) range within 18 - 35 kg/m
- •No clinically significant abnormal findings in the medical and surgical history, on the physical examination, vital sign measurements, electrocardiogram (ECG), or clinical laboratory results during Screening or Admission.
- •Written informed consent to participate in the study.
- •Capable of returning to study site for all study visits, including the initial confinement period, and willing to comply with all required study procedures.
- •Non- or ex-smoker, with ex-smoker defined as someone who completely stopped smoking for at least 6 months before day 1 of the study.
- •Sexually active males whose partners are females of childbearing potential must have agreed to use condoms from screening through at least 90 days after administration of study drug and ensured that female partner was using an acceptable form of contraception.
排除标准
- •A history of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, severe seasonal or non seasonal allergies, nasal polyps or any nasal passage abnormality that could interfere with nasal spray administration, or any other condition which, in the opinion of the Principal Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
- •Treatment with any known enzyme altering drugs such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study drug or during the entire study duration.
- •Subjects who have been on an abnormal diet (such as one that severely restricts specific basic food groups [e.g., ketogenic diet], limits calories [e.g., fast], and/or requires the use of daily supplements as a substitute for the foods typically eaten at mealtimes), during the four (4) weeks preceding the study.
- •Subjects who donated blood or plasma within 3 months of the first dose of study drug.
- •Participation in a bioequivalence study or in a clinical trial with IP administration within 80 days prior to the first dose of study drug.
- •Inadequate or difficult venous access that may jeopardize the quality or timing of the PK samples.
- •Use of any prescription or over the counter (OTC) medication within 30 days prior to the first dose of study drug or during the study.
- •Positive blood screen for HIV, Hepatitis B surface antigen (HbSAg), or Hepatitis C, or a positive screen for alcohol or drugs of abuse.
- •History of major depression or suicide attempt, or judged by the investigator as being at significant risk for suicide, violence, or homicide.
- •History of postural orthostatic tachycardia syndrome or orthostatic hypotension.
研究组 & 干预措施
7.5 mg olanzapine per 100 µL with 0.25% Intravail A3
7.5 mg olanzapine per 100 µL with 0.25% Intravail A3
干预措施: olanzapine (Drug)
7.5 mg olanzapine per 100 µL with 0.50% Intravail A3
7.5 mg olanzapine per 100 µL with 0.50% Intravail A3
干预措施: olanzapine (Drug)
olanzapine intramuscular injection
7.5 mg olanzapine per 1.5 ml of reconstituted 5.0 mg/ml solution intramuscular injection
干预措施: olanzapine (Drug)
结局指标
主要结局
(1) Bioavailability of test products compared to reference product based on pharmacokinetic parameter of AUC from time 0 to time t
时间窗: 240 hours
Characterize the pharmacokinetics of two Test Products (one product, A, is 7.5 mg olanzapine per 100 µL with 0.25% Intravail A3 as absorption enhancer and another product is, B, 7.5 mg olanzapine per 100 µL with 0.50% Intravail A3 as absorption enhancer via nasal spray) relative to Reference Product (C, intramuscular injection) after a single dose of 7.5 mg olanzapine to healthy male adults under fasting conditions.
次要结局
- (2) Bioavailability of test products compared to reference product based on pharmacokinetic parameter of Cmax(240 hours)
- (3) Bioavailability of test products compared to reference product based on pharmacokinetic parameter of AUC from time 0 to infinity(240 hours)