Pharmacodynamic Study to Compare Acute Effects of Dihydroergotamine Mesylate (DHE) on Pulmonary Arterial Pressure

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01089062

Enrollment

Registered

2010-03-18

Start date

2010-03-31

Completion date

2010-12-31

Last updated

2014-01-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Healthy volunteers

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.

Interventions

DRUGMAP0004

1.0 mg orally inhaled MAP0004 administered in Treatment B as per protocol

DRUGIV Placebo (Saline)

IV Placebo (Saline) administered in Treatment B and Treatment C as per protocol

DRUGPlacebo Inhaler

Orally inhaled Placebo administered in Treatment A and Treatment C as per protocol.

DRUGIV Dihydroergotamine Mesylate (DHE)

IV DHE administered in Treatment A as per protocol

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
AUC(0-2hrs) of Pulmonary Arterial Systolic Pressure (PASP) Over Time Post 1st Dose	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.

Secondary

Measure	Time frame	Description
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	Pulmonary artery systolic pressure (PASP) is the highest pressure exerted on the walls of the pulmonary artery.
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	Pulmonary artery systolic pressure (PASP) is the highest pressure exerted on the walls of the pulmonary artery.
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	AUC(0-4hrs) (Area Under the Curve, time 0-4 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.
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	Systolic and diastolic blood pressure measure the lowest and highest pressures against the walls of the arteries. Changes were calculated from 30 minutes pre dose (baseline) to 10 minutes post first and second dose. A positive change from baseline indicates an increase in blood pressure and a negative change indicates a decrease in blood pressure.
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	The corrected QT interval (QTc) is a measurement of the electrical impulses through the largest part of the heart muscle. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval.

Countries

United States

Participant flow

Pre-assignment details

This is a 3-treatment, 3-period, 6-sequence crossover study. Each subject received all 3 treatments in a randomly assigned order: treatments A, B, and C, the sequences were ABC, ACB, BAC, BCA, CAB, and CBA.

Participants by arm

Arm	Count
Treatment A, Then B, Then C Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose. Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose. Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose.	4
Treatment A, Then C, Then B Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose. Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose. Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose.	4
Treatment B, Then A, Then C Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose. Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose. Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose.	4
Treatment B, Then C, Then A Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose. Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose. Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose.	4
Treatment C, Then A, Then B Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose. Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose. Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose.	4
Treatment C, Then B, Then A Treatment A = inhaler placebo and IV DHE for first dose, inhaler placebo for second dose. Treatment B = MAP0004 1.0mg and IV placebo for first dose, MAP0004 1.0mg for second dose. Treatment C = inhaler placebo and IV placebo for first dose, inhaler placebo for second dose.	4
Total	24

Baseline characteristics

Characteristic	Treatment A, Then B, Then C	Treatment A, Then C, Then B	Treatment B, Then A, Then C	Treatment B, Then C, Then A	Treatment C, Then A, Then B	Treatment C, Then B, Then A	Total
Age, Continuous	26.6 years STANDARD_DEVIATION 9.2	23.4 years STANDARD_DEVIATION 3.9	28.2 years STANDARD_DEVIATION 8.2	30.3 years STANDARD_DEVIATION 4.7	26.5 years STANDARD_DEVIATION 7.4	24.8 years STANDARD_DEVIATION 7.2	26.6 years STANDARD_DEVIATION 6.6
Sex: Female, Male Female	2 Participants	4 Participants	2 Participants	4 Participants	1 Participants	3 Participants	16 Participants
Sex: Female, Male Male	2 Participants	0 Participants	2 Participants	0 Participants	3 Participants	1 Participants	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	19 / 20	10 / 20	6 / 20
serious Total, serious adverse events	0 / 20	0 / 20	0 / 20

Outcome results

Primary

AUC(0-2hrs) of Pulmonary Arterial Systolic Pressure (PASP) Over Time Post 1st 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.

Time frame: 2 hours from time of first dose