A Phase 1, Open-Label, Randomized, Crossover, Comparative Bioavailability Study of Naloxone Nasal Spray and Naloxone Hydrochloride Intramuscular Injection in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Partial Area Under the Concentration Curve (AUC) of Unconjugated Naloxone
研究概览
简要总结
The main objective of this study is to compare early exposures of two test formulations of Naloxone Nasal Spray with the reference formulation of Naloxone HCl IM Injection under fasted conditions.
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
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A minimum body weight of 50 kg and a body mass index (BMI) between 18.0 and 32.0 kilogram per square meter (kg/m2)
- •A seated blood pressure between 90 and 140 millimeters of mercury (mmHg) systolic/50 and 90 mmHg diastolic (inclusive)
- •Female subjects had a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening
排除标准
- •A known allergy or history of significant adverse reaction to naloxone, other opioids or related compounds, or to any of the excipients.
- •Any documented clinically significant infection, injury, or illness within 1 month prior to screening.
- •An active malignancy of any type, or had been diagnosed with cancer within 5 years prior to screening.
- •A documented history of alcohol or drug abuse/dependence/misuse or narcotic analgesic abuse/dependence/misuse within 2 years prior to screening. Alcohol abuse was defined as greater than 14 drinks per week.
- •Positive serology test for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at screening.
- •A positive urine test result for alcohol, drugs, or cotinine at screening or check-in.
- •A condition that the Investigator believed would have interfered with the ability to provide informed consent or comply with study instructions, or that could confound the interpretation of the study results or put the subject at undue risk.
- •Used any opioids for 30 days prior to Day
- •Required treatment with monoamine oxidase inhibitors (MAOIs) within 30 days prior to Day 1 and during the study.
- •Presence of an ongoing upper respiratory infection, rhinitis, rhinorrhea, or nasal congestion.
研究组 & 干预措施
Cohort 1: Treatment Sequence A-B-C
Participants received Treatment A on Day 1 of Period 1, Treatment B on Day 1 of Period 2, and Treatment C on Day 1 of Period 3.
干预措施: Treatment A: Naloxone Nasal Spray (Drug)
Cohort 1: Treatment Sequence A-B-C
Participants received Treatment A on Day 1 of Period 1, Treatment B on Day 1 of Period 2, and Treatment C on Day 1 of Period 3.
干预措施: Treatment B: Naloxone Nasal Spray (Drug)
Cohort 1: Treatment Sequence A-B-C
Participants received Treatment A on Day 1 of Period 1, Treatment B on Day 1 of Period 2, and Treatment C on Day 1 of Period 3.
干预措施: Treatment C: Naloxone HCL Intramuscular (IM) Injection (Drug)
Cohort 2: Treatment Sequence B-C-A
Participants received Treatment B on Day 1 of Period 1, Treatment C on Day 1 of Period 2, and Treatment A on Day 1 of Period 3.
干预措施: Treatment A: Naloxone Nasal Spray (Drug)
Cohort 2: Treatment Sequence B-C-A
Participants received Treatment B on Day 1 of Period 1, Treatment C on Day 1 of Period 2, and Treatment A on Day 1 of Period 3.
干预措施: Treatment B: Naloxone Nasal Spray (Drug)
Cohort 2: Treatment Sequence B-C-A
Participants received Treatment B on Day 1 of Period 1, Treatment C on Day 1 of Period 2, and Treatment A on Day 1 of Period 3.
干预措施: Treatment C: Naloxone HCL Intramuscular (IM) Injection (Drug)
Cohort 3: Treatment Sequence C-A-B
Participants received Treatment C on Day 1 of Period 1, Treatment A on Day 1 of Period 2, and Treatment B on Day 1 of Period 3.
干预措施: Treatment A: Naloxone Nasal Spray (Drug)
Cohort 3: Treatment Sequence C-A-B
Participants received Treatment C on Day 1 of Period 1, Treatment A on Day 1 of Period 2, and Treatment B on Day 1 of Period 3.
干预措施: Treatment B: Naloxone Nasal Spray (Drug)
Cohort 3: Treatment Sequence C-A-B
Participants received Treatment C on Day 1 of Period 1, Treatment A on Day 1 of Period 2, and Treatment B on Day 1 of Period 3.
干预措施: Treatment C: Naloxone HCL Intramuscular (IM) Injection (Drug)
Cohort 4: Treatment Sequence A-C-B
Participants received Treatment A on Day 1 of Period 1, Treatment C on Day 1 of Period 2, and Treatment B on Day 1 of Period 3.
干预措施: Treatment A: Naloxone Nasal Spray (Drug)
Cohort 4: Treatment Sequence A-C-B
Participants received Treatment A on Day 1 of Period 1, Treatment C on Day 1 of Period 2, and Treatment B on Day 1 of Period 3.
干预措施: Treatment B: Naloxone Nasal Spray (Drug)
Cohort 4: Treatment Sequence A-C-B
Participants received Treatment A on Day 1 of Period 1, Treatment C on Day 1 of Period 2, and Treatment B on Day 1 of Period 3.
干预措施: Treatment C: Naloxone HCL Intramuscular (IM) Injection (Drug)
Cohort 5: Treatment Sequence C-B-A
Participants received Treatment C on Day 1 of Period 1, Treatment B on Day 1 of Period 2, and Treatment A on Day 1 of Period 3.
干预措施: Treatment A: Naloxone Nasal Spray (Drug)
Cohort 5: Treatment Sequence C-B-A
Participants received Treatment C on Day 1 of Period 1, Treatment B on Day 1 of Period 2, and Treatment A on Day 1 of Period 3.
干预措施: Treatment B: Naloxone Nasal Spray (Drug)
Cohort 5: Treatment Sequence C-B-A
Participants received Treatment C on Day 1 of Period 1, Treatment B on Day 1 of Period 2, and Treatment A on Day 1 of Period 3.
干预措施: Treatment C: Naloxone HCL Intramuscular (IM) Injection (Drug)
Cohort 6: Treatment Sequence B-A-C
Participants received Treatment B on Day 1 of Period 1, Treatment A on Day 1 of Period 2, and Treatment C on Day 1 of Period 3.
干预措施: Treatment A: Naloxone Nasal Spray (Drug)
Cohort 6: Treatment Sequence B-A-C
Participants received Treatment B on Day 1 of Period 1, Treatment A on Day 1 of Period 2, and Treatment C on Day 1 of Period 3.
干预措施: Treatment B: Naloxone Nasal Spray (Drug)
Cohort 6: Treatment Sequence B-A-C
Participants received Treatment B on Day 1 of Period 1, Treatment A on Day 1 of Period 2, and Treatment C on Day 1 of Period 3.
干预措施: Treatment C: Naloxone HCL Intramuscular (IM) Injection (Drug)
结局指标
主要结局
Partial Area Under the Concentration Curve (AUC) of Unconjugated Naloxone
时间窗: Pre-dose and at multiple time points up to 1 hour post-dose
Plasma Concentration of Unconjugated Naloxone
时间窗: Pre-dose and at multiple time points up to 1 hour post-dose
次要结局
- Elimination Half-Life (t1/2) of Unconjugated Naloxone(Pre-dose and at multiple time points up to 24 hours post-dose)
- Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 1 up to Day 10)
- Percentage of AUC0-inf Obtained by Extrapolation (AUCextrap) of Unconjugated Naloxone(Pre-dose and at multiple time points up to 24 hours post-dose)
- Maximum Plasma Concentration (Cmax) of Unconjugated Naloxone(Pre-dose and at multiple time points up to 24 hours post-dose)
- Area Under the Curve from Time 0 to the Last Measured Concentration (AUC0-t) of Unconjugated Naloxone(Pre-dose and at multiple time points up to 24 hours post-dose)
- Area Under the Curve from Time 0 to Infinity (AUC0-inf) of Unconjugated Naloxone(Pre-dose and at multiple time points up to 24 hours post-dose)
- Time to Reach Maximum Plasma Concentration (Tmax) of Unconjugated Naloxone(Pre-dose and at multiple time points up to 24 hours post-dose)
- Last Quantifiable Concentration (Clast) of Unconjugated Naloxone(Pre-dose and at multiple time points up to 24 hours post-dose)
- Time of the Last Quantifiable Concentration (Tlast) of Unconjugated Naloxone(Pre-dose and at multiple time points up to 24 hours post-dose)
- Time Prior to the First Measurable (Non-Zero) Concentration (Tlag) of Unconjugated Naloxone(Pre-dose and at multiple time points up to 24 hours post-dose)
- Elimination Rate Constant (λz) of Unconjugated Naloxone(Pre-dose and at multiple time points up to 24 hours post-dose)