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

Keywords

• Healthy volunteers

Lead sponsor

Allergan is the lead sponsor of 499 studies on the registry; none are open to participants now.

Of its 91 completed or terminated interventional studies of FDA-regulated products, 89 (98%) have results posted.

Study arms

• Other
  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 · Drug: IV Placebo (Saline) · Drug: Placebo Inhaler · Drug: IV Dihydroergotamine Mesylate (DHE)

• Other
  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 · Drug: IV Placebo (Saline) · Drug: Placebo Inhaler · Drug: IV Dihydroergotamine Mesylate (DHE)

• Other
  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 · Drug: IV Placebo (Saline) · Drug: Placebo Inhaler · Drug: IV Dihydroergotamine Mesylate (DHE)

• Other
  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 · Drug: IV Placebo (Saline) · Drug: Placebo Inhaler · Drug: IV Dihydroergotamine Mesylate (DHE)

• Other
  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 · Drug: IV Placebo (Saline) · Drug: Placebo Inhaler · Drug: IV Dihydroergotamine Mesylate (DHE)

• Other
  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 · Drug: IV Placebo (Saline) · Drug: Placebo Inhaler · Drug: IV Dihydroergotamine Mesylate (DHE)

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

  Also known as: D.H.E.45®

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.

   Time frame: 2 hours from time of first dose

Secondary outcomes

1. Percent of Subjects With an Increase in PASP Greater Than 10mmHg From Baseline to 2 Hours From the First Dose

   Pulmonary artery systolic pressure (PASP) is the highest pressure exerted on the walls of the pulmonary artery.

   Time frame: baseline and 2 hours from the time of first dose

2. Maximum Change in PASP From Baseline to the Two Hour Period Following the First Dose

   Pulmonary artery systolic pressure (PASP) is the highest pressure exerted on the walls of the pulmonary artery.

   Time frame: baseline and 2 hours from the time of first dose

3. AUC(0-4hrs) of Pulmonary Arterial Systolic Pressure (PASP) From the Start of the First Dose to Two Hours After the Second 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.

   Time frame: 4 hours from the time of first dose

4. Change in Blood Pressure From Baseline After the Two 2-hour Post Dosing Periods

   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.

   Time frame: baseline, 10 minutes post 1st dose, 10 minutes post 2nd dose

5. Change From Baseline in QTc Interval at 14 Minutes After the 1st and 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.

   Time frame: baseline, 14 minutes from time of 1st dose, 14 minutes from time of 2nd dose

Baseline characteristics

Publications

• 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. PubMed 23926420 ↗