A Randomized, Double Blind, Placebo Controlled, Three-Period Crossover Study Comparing the Acute Effects of Intravenous Dihydroergotamine (DHE) and Orally Inhaled DHE (MAP0004) on Pulmonary Arterial Pressure and Tolerability in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Allergan
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- AUC(0-2hrs) of Pulmonary Arterial Systolic Pressure (PASP) Over Time Post 1st Dose
研究概览
简要总结
Compare the acute effects and tolerability of Dihydroergotamine Mesylate (DHE) delivered by Oral Inhalation (MAP0004) versus by intravenous (IV) infusion in healthy adult volunteers.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Able to provide a signed, executed written informed consent
- •Healthy non-smoking adult volunteers: Male or Female subjects 18 to 45 years old
- •Female subjects who are practicing adequate contraception
- •Stable cardiac status
- •Normal hemoglobin values
- •Normal Echocardiogram
- •Normal or not clinically significant 12-lead Electrocardiogram
- •Demonstrated ability to properly use the Tempo® Inhaler
- •Subject has not donated blood in the last 56 days
排除标准
- •Contraindication to dihydroergotamine mesylate (DHE)
- •Use of any excluded concomitant medications within the 10 days prior to Visit 1
- •History of hemiplegic or basilar migraine
- •Participation in another investigational trial during the 30 days prior to Visit 1
研究组 & 干预措施
Treatment A, then Treatment B, then Treatment C
The second dose in each treatment group (A,B,C) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 2.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 3.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 4.
干预措施: Placebo Inhaler (Drug)
Treatment A, then Treatment B, then Treatment C
The second dose in each treatment group (A,B,C) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 2.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 3.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 4.
干预措施: MAP0004 (Drug)
Treatment A, then Treatment B, then Treatment C
The second dose in each treatment group (A,B,C) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 2.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 3.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 4.
干预措施: IV Placebo (Saline) (Drug)
Treatment A, then Treatment B, then Treatment C
The second dose in each treatment group (A,B,C) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 2.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 3.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 4.
干预措施: IV Dihydroergotamine Mesylate (DHE) (Drug)
Treatment A, then Treatment C, then Treatment B
The second dose in each treatment group (A,C,B) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 2.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 3.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 4.
干预措施: MAP0004 (Drug)
Treatment A, then Treatment C, then Treatment B
The second dose in each treatment group (A,C,B) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 2.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 3.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 4.
干预措施: IV Placebo (Saline) (Drug)
Treatment A, then Treatment C, then Treatment B
The second dose in each treatment group (A,C,B) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 2.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 3.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 4.
干预措施: Placebo Inhaler (Drug)
Treatment A, then Treatment C, then Treatment B
The second dose in each treatment group (A,C,B) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 2.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 3.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 4.
干预措施: IV Dihydroergotamine Mesylate (DHE) (Drug)
Treatment B, then Treatment A, then Treatment C
The second dose in each treatment group (B,A,C) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 2.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 3.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 4.
干预措施: MAP0004 (Drug)
Treatment B, then Treatment A, then Treatment C
The second dose in each treatment group (B,A,C) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 2.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 3.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 4.
干预措施: IV Placebo (Saline) (Drug)
Treatment B, then Treatment A, then Treatment C
The second dose in each treatment group (B,A,C) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 2.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 3.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 4.
干预措施: Placebo Inhaler (Drug)
Treatment B, then Treatment A, then Treatment C
The second dose in each treatment group (B,A,C) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 2.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 3.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 4.
干预措施: IV Dihydroergotamine Mesylate (DHE) (Drug)
Treatment B, then Treatment C, then Treatment A
The second dose in each treatment group (B,C,A) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 2.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 3.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 4.
干预措施: MAP0004 (Drug)
Treatment B, then Treatment C, then Treatment A
The second dose in each treatment group (B,C,A) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 2.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 3.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 4.
干预措施: IV Placebo (Saline) (Drug)
Treatment B, then Treatment C, then Treatment A
The second dose in each treatment group (B,C,A) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 2.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 3.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 4.
干预措施: Placebo Inhaler (Drug)
Treatment B, then Treatment C, then Treatment A
The second dose in each treatment group (B,C,A) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 2.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 3.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 4.
干预措施: IV Dihydroergotamine Mesylate (DHE) (Drug)
Treatment C, then Treatment A, then Treatment B
The second dose in each treatment group (C,A,B) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 2.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 3.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 4.
干预措施: MAP0004 (Drug)
Treatment C, then Treatment A, then Treatment B
The second dose in each treatment group (C,A,B) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 2.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 3.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 4.
干预措施: IV Placebo (Saline) (Drug)
Treatment C, then Treatment A, then Treatment B
The second dose in each treatment group (C,A,B) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 2.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 3.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 4.
干预措施: Placebo Inhaler (Drug)
Treatment C, then Treatment A, then Treatment B
The second dose in each treatment group (C,A,B) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 2.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 3.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 4.
干预措施: IV Dihydroergotamine Mesylate (DHE) (Drug)
Treatment C, then Treatment B, then Treatment A
The second dose in each treatment group (C,B,A) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 2.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 3.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 4.
干预措施: MAP0004 (Drug)
Treatment C, then Treatment B, then Treatment A
The second dose in each treatment group (C,B,A) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 2.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 3.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 4.
干预措施: IV Placebo (Saline) (Drug)
Treatment C, then Treatment B, then Treatment A
The second dose in each treatment group (C,B,A) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 2.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 3.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 4.
干预措施: Placebo Inhaler (Drug)
Treatment C, then Treatment B, then Treatment A
The second dose in each treatment group (C,B,A) was given two hours from the time of the first dose. There were 7-11 days between each treatment visit.
Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose at Visit 2.
Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose at Visit 3.
Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose at Visit 4.
干预措施: IV Dihydroergotamine Mesylate (DHE) (Drug)
结局指标
主要结局
AUC(0-2hrs) of Pulmonary Arterial Systolic Pressure (PASP) Over Time Post 1st Dose
时间窗: 2 hours from time of first dose
AUC(0-2hrs) (Area Under the Curve, time 0-2 hours post-1st dose) in PASP millimeters of mercury times minutes (mmHg\*min). PASP is the highest pressure exerted on the walls of the pulmonary artery.
次要结局
- Change in Blood Pressure From Baseline After the Two 2-hour Post Dosing Periods(baseline, 10 minutes post 1st dose, 10 minutes post 2nd dose)
- Percent of Subjects With an Increase in PASP Greater Than 10mmHg From Baseline to 2 Hours From the First Dose(baseline and 2 hours from the time of first dose)
- Maximum Change in PASP From Baseline to the Two Hour Period Following the First Dose(baseline and 2 hours from the time of first dose)
- AUC(0-4hrs) of Pulmonary Arterial Systolic Pressure (PASP) From the Start of the First Dose to Two Hours After the Second Dose(4 hours from the time of first dose)
- Change From Baseline in QTc Interval at 14 Minutes After the 1st and 2nd Dose(baseline, 14 minutes from time of 1st dose, 14 minutes from time of 2nd dose)