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

This study has been completed.
Sponsor:
Collaborator:
MAP Pharmaceuticals, Inc., a wholly owned subsidiary of Allergan
Information provided by (Responsible Party):
Allergan
ClinicalTrials.gov Identifier:
NCT01089062
First received: March 17, 2010
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Healthy
Drug: MAP0004
Drug: IV Placebo (Saline)
Drug: Placebo Inhaler
Drug: IV Dihydroergotamine Mesylate (DHE)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Allergan:

Primary Outcome Measures:
  • AUC(0-2hrs) of Pulmonary Arterial Systolic Pressure (PASP) Over Time Post 1st Dose [ Time Frame: 2 hours from time of first dose ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Percent of Subjects With an Increase in PASP Greater Than 10mmHg From Baseline to 2 Hours From the First Dose [ Time Frame: baseline and 2 hours from the time of first dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: baseline and 2 hours from the time of first dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 4 hours from the time of first dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline, 10 minutes post 1st dose, 10 minutes post 2nd dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: baseline, 14 minutes from time of 1st dose, 14 minutes from time of 2nd dose ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 24
Study Start Date: March 2010
Study Completion Date: December 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: MAP0004
1.0 mg orally inhaled MAP0004 administered in Treatment B as per protocol
Drug: IV Placebo (Saline)
IV Placebo (Saline) administered in Treatment B and Treatment C as per protocol
Drug: Placebo Inhaler
Orally inhaled Placebo administered in Treatment A and Treatment C as per protocol.
Drug: IV Dihydroergotamine Mesylate (DHE)
IV DHE administered in Treatment A as per protocol
Other Name: D.H.E.45®
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.

Drug: MAP0004
1.0 mg orally inhaled MAP0004 administered in Treatment B as per protocol
Drug: IV Placebo (Saline)
IV Placebo (Saline) administered in Treatment B and Treatment C as per protocol
Drug: Placebo Inhaler
Orally inhaled Placebo administered in Treatment A and Treatment C as per protocol.
Drug: IV Dihydroergotamine Mesylate (DHE)
IV DHE administered in Treatment A as per protocol
Other Name: D.H.E.45®
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.

Drug: MAP0004
1.0 mg orally inhaled MAP0004 administered in Treatment B as per protocol
Drug: IV Placebo (Saline)
IV Placebo (Saline) administered in Treatment B and Treatment C as per protocol
Drug: Placebo Inhaler
Orally inhaled Placebo administered in Treatment A and Treatment C as per protocol.
Drug: IV Dihydroergotamine Mesylate (DHE)
IV DHE administered in Treatment A as per protocol
Other Name: D.H.E.45®
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.

Drug: MAP0004
1.0 mg orally inhaled MAP0004 administered in Treatment B as per protocol
Drug: IV Placebo (Saline)
IV Placebo (Saline) administered in Treatment B and Treatment C as per protocol
Drug: Placebo Inhaler
Orally inhaled Placebo administered in Treatment A and Treatment C as per protocol.
Drug: IV Dihydroergotamine Mesylate (DHE)
IV DHE administered in Treatment A as per protocol
Other Name: D.H.E.45®
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.

Drug: MAP0004
1.0 mg orally inhaled MAP0004 administered in Treatment B as per protocol
Drug: IV Placebo (Saline)
IV Placebo (Saline) administered in Treatment B and Treatment C as per protocol
Drug: Placebo Inhaler
Orally inhaled Placebo administered in Treatment A and Treatment C as per protocol.
Drug: IV Dihydroergotamine Mesylate (DHE)
IV DHE administered in Treatment A as per protocol
Other Name: D.H.E.45®
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.

Drug: MAP0004
1.0 mg orally inhaled MAP0004 administered in Treatment B as per protocol
Drug: IV Placebo (Saline)
IV Placebo (Saline) administered in Treatment B and Treatment C as per protocol
Drug: Placebo Inhaler
Orally inhaled Placebo administered in Treatment A and Treatment C as per protocol.
Drug: IV Dihydroergotamine Mesylate (DHE)
IV DHE administered in Treatment A as per protocol
Other Name: D.H.E.45®

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01089062

Locations
United States, North Carolina
Duke Clinical Research Unit
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Allergan
MAP Pharmaceuticals, Inc., a wholly owned subsidiary of Allergan
Investigators
Principal Investigator: Robert J Noveck, M.D., Ph.D. Duke Clinical Research Unit
  More Information

No publications provided by Allergan

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Allergan
ClinicalTrials.gov Identifier: NCT01089062     History of Changes
Other Study ID Numbers: MAP0004-CL-P102
Study First Received: March 17, 2010
Results First Received: August 19, 2013
Last Updated: December 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Allergan:
Healthy volunteers

Additional relevant MeSH terms:
Dihydroergotamine
Analgesics
Analgesics, Non-Narcotic
Cardiovascular Agents
Central Nervous System Agents
Dopamine Agents
Dopamine Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on November 20, 2014