Bioavailability of Nasal Naloxone and Injected Naloxone Compared. A Randomized, Open Label, 4-way Cross-over Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Difference in Peak plasma concentration (Cmax)
研究概览
简要总结
Opioid overdoses have in the last decade counted for about 230 untimely deaths annually in Norway. The government is currently implementing a strategy for combating this epidemic. Among the actions promoted in this strategy is the distribution of naloxone for intranasal administration. Such administration of naloxone is currently being implemented and tried out around the world, but very little has been done to pharmacologically study this new route of administration of this well known drug, and only 3 open label randomized controlled trials (RCTs) have been conducted. A recent guideline from the WHO on community management of opioid overdoses is a comprehensive review of many of the aspects the investigators cover in our research.
Regarding both dosage, routes of administration of naloxone and care of these patients in the pre hospital setting. The WHO calls for nasal formulations with a higher concentration, as well as focuses on the current wide spread off label use of nasal naloxone as a problem and identifies several research questions of critical importance and very low evidence.The current study, together with our research group's previous and future studies, aims to provide data for the development of a medicinal product with marketing authorisation for use in pre-hospital overdoses. This to contribute to public health measures for opioid users and those around them.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •In order to participate in this study the subjects must meet all of the following inclusion criteria:
- •Provision of a signed written informed consent
- •ECG without any pathological abnormalities
- •Have a BMI range of 18.5- 26.0 kg/m
- •Female subject with child bearing potential must use high efficacy contraception. For the purpose of this study acceptable contraception is defined as sterilization, oral contraceptives, patch, implants, vaginal ring, hormonal IUD or copper IUD through out the study until the last visit.
- •Laboratory values within reference values for the following haematology and biochemistry tests:
- •Haemoglobin
- •Creatinine
排除标准
- •In order to participate in the study subjects must not meet any of the following exclusion criteria:
- •using medication on a regular basis, including regular use of nasal spray of any form.
- •History of prior drug allergy
- •local nasal disease or nasal surgery for the last 2 months
- •Pregnant or breast feeding women. A serum HCG below 3 U/L must be demonstrated in females of child-bearing potential at Screening Visit.
- •Current drug or alcohol abuse, which in the opinion of the Investigator should preclude participation in the study.
- •Having received another new medical chemical entity (defined as a compound which has not been approved for marketing) or having participated in any other clinical study that included drug treatment within 3 months of the administration of investigational product in this study.
- •Hypersensitivity to naloxone or any of its excipients.
- •Investigator considers subject unlikely to comply with study procedures, restrictions and/or other requirements.
研究组 & 干预措施
Intranasal naloxone 1x
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intranasal (IN) naloxone 1x (Drug)
Intranasal naloxone 1x
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intranasal (IN) naloxone 2 (Drug)
Intranasal naloxone 1x
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intravenous (IV) naloxone (Drug)
Intranasal naloxone 1x
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intramuscular (IM) naloxone (Drug)
Intranasal naloxone 2x
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intranasal (IN) naloxone 1x (Drug)
Intranasal naloxone 2x
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intranasal (IN) naloxone 2 (Drug)
Intranasal naloxone 2x
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intravenous (IV) naloxone (Drug)
Intranasal naloxone 2x
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intramuscular (IM) naloxone (Drug)
Intravenous naloxone
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intranasal (IN) naloxone 1x (Drug)
Intravenous naloxone
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intranasal (IN) naloxone 2 (Drug)
Intravenous naloxone
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intravenous (IV) naloxone (Drug)
Intravenous naloxone
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intramuscular (IM) naloxone (Drug)
Intramuscular naloxone
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intranasal (IN) naloxone 1x (Drug)
Intramuscular naloxone
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intranasal (IN) naloxone 2 (Drug)
Intramuscular naloxone
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intravenous (IV) naloxone (Drug)
Intramuscular naloxone
Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
干预措施: Intramuscular (IM) naloxone (Drug)
结局指标
主要结局
Difference in Peak plasma concentration (Cmax)
时间窗: 4 days
Cmax will be compared for single dose IN, IM and IV naloxone
Difference in systemic exposure: Area under the plasma concentration versus time curve (AUC-0last)
时间窗: 4 days
AUC 0-last will be compared for single dose IN, IM and IV naloxone
Difference in dose adjusted systemic exposure: Area under the plasma concentration versus time curve (AUC-0inf)
时间窗: 4 days
AUC0-inf will be compared for single dose IN, IM and IV naloxone
Difference in time at which the Cmax is observed (Tmax)
时间窗: 4 days
Tmax will be compared for single dose IN, IM and IV naloxone
次要结局
- Dose proportionality(4 days)
- Absolute bioavailability(4 days)
- Relative bioavailability(4 days)