Clinical trial NCT01089062: Pharmacodynamic Study to Compare Acute Effects of Dihydroergotamine Mesylate (DHE) on Pulmonary Arterial Pressure
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy volunteers
Lead sponsor: Allergan
Sponsor class: INDUSTRY
Collaborators: name: MAP Pharmaceuticals, Inc., a wholly owned subsidiary of Allergan
First posted: 2010-03-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Compare the acute effects and tolerability of Dihydroergotamine Mesylate (DHE) delivered by Oral Inhalation (MAP0004) versus by intravenous (IV) infusion in healthy adult volunteers.


Eligibility criteria: Inclusion Criteria:

1. Able to provide a signed, executed written informed consent
2. Healthy non-smoking adult volunteers: Male or Female subjects 18 to 45 years old
3. Female subjects who are practicing adequate contraception
4. Stable cardiac status
5. Normal hemoglobin values
6. Normal Echocardiogram
7. Normal or not clinically significant 12-lead Electrocardiogram
8. Demonstrated ability to properly use the Tempo® Inhaler
9. Subject has not donated blood in the last 56 days

Exclusion Criteria:

1. Contraindication to dihydroergotamine mesylate (DHE)
2. Use of any excluded concomitant medications within the 10 days prior to Visit 1
3. History of hemiplegic or basilar migraine
4. Participation in another investigational trial during the 30 days prior to Visit 1

Primary outcomes:
measure: AUC(0-2hrs) of Pulmonary Arterial Systolic Pressure (PASP) Over Time Post 1st Dose
timeFrame: 2 hours from time of first dose
Secondary outcomes:
measure: Percent of Subjects With an Increase in PASP Greater Than 10mmHg From Baseline to 2 Hours From the First Dose
timeFrame: baseline and 2 hours from the time of first dose
measure: Maximum Change in PASP From Baseline to the Two Hour Period Following the First Dose
timeFrame: baseline and 2 hours from the time of first dose
measure: AUC(0-4hrs) of Pulmonary Arterial Systolic Pressure (PASP) From the Start of the First Dose to Two Hours After the Second Dose
timeFrame: 4 hours from the time of first dose
measure: Change in Blood Pressure From Baseline After the Two 2-hour Post Dosing Periods
timeFrame: baseline, 10 minutes post 1st dose, 10 minutes post 2nd dose
measure: Change From Baseline in QTc Interval at 14 Minutes After the 1st and 2nd Dose
timeFrame: baseline, 14 minutes from time of 1st dose, 14 minutes from time of 2nd dose
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Clinical Research Unit
state: North Carolina
Study officials:
affiliation: Duke Clinical Research Unit
name: Robert J Noveck, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Noveck RJ, Douglas PS, Chow SC, Mangum B, Kori S, Kellerman DJ. Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine. Drug Des Devel Ther. 2013 Jul 24;7:619-25. doi: 10.2147/DDDT.S44093. Print 2013.