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

NCT01089062 | Completed Phase 1 Results

• 1 other identifier: MAP0004-CL-P102
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Healthy volunteers

Outcome Measures

Primary Outcomes (1)

• 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.

  2 hours from time of first dose

Secondary Outcomes (5)

• 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 in Blood Pressure From Baseline After the Two 2-hour Post Dosing Periods

  baseline, 10 minutes post 1st dose, 10 minutes post 2nd 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

Study Arms (6)

Treatment A, then Treatment B, then Treatment C

OTHER

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; Drug: IV Placebo (Saline); Drug: Placebo Inhaler; Drug: IV Dihydroergotamine Mesylate (DHE)

Treatment A, then Treatment C, then Treatment B

OTHER

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; Drug: IV Placebo (Saline); Drug: Placebo Inhaler; Drug: IV Dihydroergotamine Mesylate (DHE)

Treatment B, then Treatment A, then Treatment C

OTHER

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; Drug: IV Placebo (Saline); Drug: Placebo Inhaler; Drug: IV Dihydroergotamine Mesylate (DHE)

Treatment B, then Treatment C, then Treatment A

OTHER

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; Drug: IV Placebo (Saline); Drug: Placebo Inhaler; Drug: IV Dihydroergotamine Mesylate (DHE)

Treatment C, then Treatment A, then Treatment B

OTHER

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; Drug: IV Placebo (Saline); Drug: Placebo Inhaler; Drug: IV Dihydroergotamine Mesylate (DHE)

Treatment C, then Treatment B, then Treatment A

OTHER

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; Drug: IV Placebo (Saline); Drug: Placebo Inhaler; Drug: IV Dihydroergotamine Mesylate (DHE)

Interventions

MAP0004 DRUG

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

Treatment A, then Treatment B, then Treatment C; Treatment A, then Treatment C, then Treatment B; Treatment B, then Treatment A, then Treatment C; Treatment B, then Treatment C, then Treatment A; Treatment C, then Treatment A, then Treatment B; Treatment C, then Treatment B, then Treatment A

IV Placebo (Saline) DRUG

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

Treatment A, then Treatment B, then Treatment C; Treatment A, then Treatment C, then Treatment B; Treatment B, then Treatment A, then Treatment C; Treatment B, then Treatment C, then Treatment A; Treatment C, then Treatment A, then Treatment B; Treatment C, then Treatment B, then Treatment A

Placebo Inhaler DRUG

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

Treatment A, then Treatment B, then Treatment C; Treatment A, then Treatment C, then Treatment B; Treatment B, then Treatment A, then Treatment C; Treatment B, then Treatment C, then Treatment A; Treatment C, then Treatment A, then Treatment B; Treatment C, then Treatment B, then Treatment A

IV Dihydroergotamine Mesylate (DHE) DRUG

IV DHE administered in Treatment A as per protocol

Also known as: D.H.E.45®

Treatment A, then Treatment B, then Treatment C; Treatment A, then Treatment C, then Treatment B; Treatment B, then Treatment A, then Treatment C; Treatment B, then Treatment C, then Treatment A; Treatment C, then Treatment A, then Treatment B; Treatment C, then Treatment B, then Treatment A

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Allergan: lead
• MAP Pharmaceuticals, Inc., a wholly owned subsidiary of Allergan: collaborator

Study Sites (1)

Duke Clinical Research Unit

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  PMID: 23926420 DERIVED

MeSH Terms

Interventions

Sodium Chloride; Dihydroergotamine

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Ergotamines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: VP, Scientific Affairs
• Organization: MAP Pharmaceuticals Inc., a wholly owned subsidiary of Allergan

dkellerman@mappharma.com

650-386-3100

Study Officials

• Robert J Noveck, M.D., Ph.D.

  Duke Clinical Research Unit

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2010
• First Posted: March 18, 2010
• Study Start: March 1, 2010
• Primary Completion: September 1, 2010
• Study Completion: December 1, 2010
• Last Updated: January 9, 2014
• Results First Posted: October 22, 2013

Record last verified: 2013-12

Locations

US (1)