A Phase-1, Open-label Randomized, 4-treatment, 4-period Crossover Study to Evaluate the Pharmacokinetics, Relative Bioavailability, Safety and Tolerability of Single Doses of Dihydroergotamine Mesylate (DHE) Inhalation Powder, DHE Intravenous (IV), and DHE Nasal Spray in Healthy Adult Subjects.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Pharmacokinetics: Area under the curve (AUC 0-t) of DHE
研究概览
简要总结
A Phase 1 clinical trial to evaluate the pharmacokinetics, relative bioavailability, safety and tolerability of DHE inhalation powder delivered by dry powder inhaler, DHE IV, and DHE nasal spray.
详细描述
This is an open-label, randomized, 4-treatment, 4-period crossover study to evaluate the PK, relative BA, safety, and tolerability of single doses of study medication in healthy adult subjects.
Following screening, eligible subjects will be enrolled and randomized to one of the 4 treatment sequences. Subjects will receive single doses of DHE inhalation powder (low dose and high dose), DHE IV (1 mg) and DHE nasal spray (2 mg).
Subjects will be administered one treatment in each period according to their assigned sequence. Each subject will receive all 4 treatments in the study.
During each treatment period subjects will remain in the clinical research unit for 3 days, until completion of the 48-hour post-dose assessments.
Subjects will return for their next treatment period after at least 7 days washout after the administration of their previous treatment until all periods have been completed in their sequence.
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
盲法说明
None (open-label)
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
- •Subjects must meet all the following criteria to be included in the study:
- •Male or female, ≥ 18 and ≤ 55 years of age, with body mass index (BMI) >18.5 and < 32.0 kg/m2
- •Healthy subjects
- •Female subjects of non-childbearing potential or childbearing potential willing to use protocol required methods of contraception
- •Current non-smoker
- •Able to understand the study procedures and provide signed informed consent to participate in the study.
排除标准
- •Subjects to whom any of the following applies will be excluded from the study:
- •Positive pregnancy test or lactating female subjects at screening or on Day 1 of each treatment period
- •Clinically significant abnormal laboratory or serology test results
- •History or current diagnosis of uncontrolled or significant cardiac disease
- •Significant risk factors for cardiovascular disease
- •Subject with abnormal lung function at screening
- •History or current diagnosis of lung disease e.g. asthma, COPD
- •Known allergic reactions, hypersensitivity or contraindications to DHE, other ergot-derived products or to any excipient
- •History of drug or alcohol abuse
研究组 & 干预措施
Treatment A: inhaled DHE low dose
Low dose of DHE inhalation powder
干预措施: DHE inhalation powder low dose administered via dry powder inhaler (DPI) device (Combination Product)
Treatment B: inhaled DHE high dose
High dose of DHE inhalation powder
干预措施: DHE inhalation powder high dose administered via dry powder inhaler (DPI) device (Combination Product)
Treatment C: intravenous DHE
1 mg DHE injected intravenously
干预措施: DHE injected intravenously (1 mg) (Drug)
Treatment C: intravenous DHE
1 mg DHE injected intravenously
干预措施: Metoclopramide 10mg (Drug)
Treatment D: intranasal DHE
2 mg DHE nasal spray (Migranal®)
干预措施: DHE 2 mg administered by nasal spray (Migranal®) (Drug)
结局指标
主要结局
Pharmacokinetics: Area under the curve (AUC 0-t) of DHE
时间窗: For each of the 4 treatment periods on baseline and post-dose measurements from 2 minutes up to 48 hours
Area under the concentration-time curve from time zero until the last observed plasma concentration of DHE (AUC 0-t)
Pharmacokinetics: Area under the curve (AUC 0-inf) of DHE
时间窗: For each of the 4 treatment periods on baseline and post-dose measurements from 2 minutes up to 48 hours
Area under the concentration-time curve from time zero to infinity (extrapolated) of plasma concentrations of DHE (AUC 0-inf)
Pharmacokinetics: Peak plasma concentration (C max) of DHE
时间窗: For each of the 4 treatment periods on baseline and post-dose measurements from 2 minutes up to 48 hours
Maximal observed plasma concentration of DHE (C max)
次要结局
- Safety: Number of participants with adverse events(From the time of signing the informed consent until the last visit on Day 7 after the last treatment period)
- Physical examination(At screening, and for each of the 4 treatment periods at baseline, and post-dose at day 2 and day 3)
- Lung function by spirometry : Forced Expiratory Volume in 1 sec in % of predicted normal (FEV1 )(At screening, and for each of the 4 treatment periods at pre-dose, and post-dose up to 48 hours)
- Lung function by spirometry : Forced Vital Capacity (FVC) in liters(At screening, and for each of the 4 treatment periods at pre-dose, and post-dose up to 48 hours)
- Lung function by spirometry : FEV1/FVC ratio(At screening, and for each of the 4 treatment periods at pre-dose, and post-dose up to 48 hours)
- Lung function by spirometry : Forced Expiratory Flow 25-75 in %(At screening, and for each of the 4 treatment periods at pre-dose, and post-dose up to 48 hours)
- Clinical laboratory tests blood and urine(At screening, and for each of the 4 treatment periods at pre-dose, and post-dose up to 48 hours)
- Pharmacokinetics: Volume of distribution of DHE (Vz)(For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours)
- Pharmacokinetics: Area under the curve (AUC 0-t) of 8'-OH-DHE(For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours)
- Pharmacokinetics: Area under the curve (AUC 0-inf) of 8'-OH-DHE(For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours)
- Pharmacokinetics: Peak plasma concentration (C max) of 8'-OH-DHE(For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours)
- Pharmacokinetics: Time of peak maximal concentration (T max) of DHE and 8'-OH-DHE(For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours)
- Pharmacokinetics: Terminal elimination half-life (T 1/2 el) of DHE and 8'-OH-DHE(For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours)
- Pharmacokinetics: Area under the curve (AUC 0-30 min) of DHE(For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours)
- Pharmacokinetics: Area under the curve (AUC 0-2 hours) of DHE(For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours)
- Pharmacokinetics: Apparent clearance of DHE (CL/F)(For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours)
- Pharmacokinetics: Clearance of DHE (CL)(For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours)
- Pharmacokinetics: Apparent volume of distribution of DHE (Vz/F)(For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours)
- Safety: Blood pressure in mmHg(Baseline and post-dose measurements from 10 minutes up to 48 hours for each of the 4 treatment periods)
- Safety: Heart rate in beats/min(Baseline and post-dose measurements from 10 minutes up to 48 hours for each of the 4 treatment periods)
- Safety: Respiratory rate in breaths/min(Baseline and post-dose measurements from 10 minutes up to 48 hours for each of the 4 treatment periods)
- Safety: Oral body temperature in degree Celsius(Baseline and post-dose measurements from 10 minutes up to 48 hours for each of the 4 treatment periods)
- ECG PR interval in msec(Baseline and post-dose measurements from 10 minutes up to 4 hours for each of the 4 treatment periods)
- ECG QRS complex in msec(Baseline and post-dose measurements from 10 minutes up to 4 hours for each of the 4 treatment periods)
- ECG QT interval in msec(Baseline and post-dose measurements from 10 minutes up to 4 hours for each of the 4 treatment periods)