QT Intervals Study to Compare the Acute Effects of Orally Inhaled Dihydroergotamine (DHE), Oral Moxifloxacin, and Placebo

A Randomized, Double Blind, Placebo Controlled, Three- Period Crossover Study Comparing the Acute Effects of Orally Inhaled Dihydroergotamine (DHE), Oral Moxifloxacin, and Placebo on QT Intervals in Healthy Adults

Compare the acute effect on the QT interval of MAP0004 (Dihydroergotamine Mesylate delivered by Oral Inhalation) with Moxifloxacin and Placebo.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: MAP0004; Drug: Inhaler Placebo; Drug: Moxifloxacin; Drug: Placebo Capsule

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Dakota
    • Fargo, North Dakota, United States
      • Cetero Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 (see section 4.4) or who are sterile
4. No known cardiac disease
5. Normal hemoglobin values

6. Normal or not clinically significant 12-lead Electrocardiogram

   • Heart rate ≥ 40 and ≤ 100 at Visit 1 vital signs assessment (resting)
   • Subjects with QTcF interval duration <430 msec for males and <450 msec for females obtained from the ECG recorder's measurements on the screening ECG taken after at least 5 minutes of quiet rest in supine position
7. Demonstrated ability to properly use the Tempo® Inhaler
8. Subject has not donated blood in the last 56 days

Exclusion Criteria:

1. Contraindication to dihydroergotamine mesylate (DHE)
2. History of hemiplegic or basilar migraine
3. Family history of long QT syndrome
4. Participation in another investigational trial during the 30 days prior to Visit 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Treatment A, then Treatment B, then Treatment C; There was 48 hour wash-out between treatment visits. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 2. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 3. Treatment C = inhaler placebo and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing.	Drug: MAP0004; 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol; Drug: Inhaler Placebo; Placebo for Inhaler administered in Treatments A and C; Drug: Moxifloxacin; 400mg encapsulated tablet administered in Treatment A as per protocol; Other Names: Avelox®; Drug: Placebo Capsule; Placebo for Moxifloxacin administered in Treatment B and Treatment C
OTHER: Treatment A, then Treatment C, then Treatment B; There was 48 hour wash-out between treatment visits. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 2. Treatment C = inhaler placebo and placebo capsules at Visit 3. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing.	Drug: MAP0004; 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol; Drug: Inhaler Placebo; Placebo for Inhaler administered in Treatments A and C; Drug: Moxifloxacin; 400mg encapsulated tablet administered in Treatment A as per protocol; Other Names: Avelox®; Drug: Placebo Capsule; Placebo for Moxifloxacin administered in Treatment B and Treatment C
OTHER: Treatment B, then Treatment A, then Treatment C; There was 48 hour wash-out between treatment visits. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 2. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 3. Treatment C = inhaler placebo and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing.	Drug: MAP0004; 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol; Drug: Inhaler Placebo; Placebo for Inhaler administered in Treatments A and C; Drug: Moxifloxacin; 400mg encapsulated tablet administered in Treatment A as per protocol; Other Names: Avelox®; Drug: Placebo Capsule; Placebo for Moxifloxacin administered in Treatment B and Treatment C
OTHER: Treatment B, then Treatment C, then Treatment A; There was 48 hour wash-out between treatment visits. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 2. Treatment C = inhaler placebo and placebo capsules at Visit 3. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 4. Tablets were orally administered after oral inhalation dosing.	Drug: MAP0004; 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol; Drug: Inhaler Placebo; Placebo for Inhaler administered in Treatments A and C; Drug: Moxifloxacin; 400mg encapsulated tablet administered in Treatment A as per protocol; Other Names: Avelox®; Drug: Placebo Capsule; Placebo for Moxifloxacin administered in Treatment B and Treatment C
OTHER: Treatment C, then Treatment A, then Treatment B; There was 48 hour wash-out between treatment visits. Treatment C = inhaler placebo and placebo capsules at Visit 2. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 3. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing.	Drug: MAP0004; 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol; Drug: Inhaler Placebo; Placebo for Inhaler administered in Treatments A and C; Drug: Moxifloxacin; 400mg encapsulated tablet administered in Treatment A as per protocol; Other Names: Avelox®; Drug: Placebo Capsule; Placebo for Moxifloxacin administered in Treatment B and Treatment C
OTHER: Treatment C, then Treatment B, then Treatment A; There was 48 hour wash-out between treatment visits. Treatment C = inhaler placebo and placebo capsules at Visit 2. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 3. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 4. Tablets were orally administered after oral inhalation dosing.	Drug: MAP0004; 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol; Drug: Inhaler Placebo; Placebo for Inhaler administered in Treatments A and C; Drug: Moxifloxacin; 400mg encapsulated tablet administered in Treatment A as per protocol; Other Names: Avelox®; Drug: Placebo Capsule; Placebo for Moxifloxacin administered in Treatment B and Treatment C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in QTcI for MAP0004 3.0mg and Placebo at 30 Minutes	The corrected QT interval, individualized (QTcI) is a measurement of the electrical impulses through the largest part of the heart muscle individualized for subject pre-dose values. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval.	baseline and 30 minutes
Change From Baseline in QTcI for MAP0004 3.0mg, Placebo, and Moxifloxacin at 2 Hours	The corrected QT interval, individualized (QTcI) is a measurement of the electrical impulses through the largest part of the heart muscle individualized for subject pre-dose values. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval.	baseline and 2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in QTcF for MAP0004 3.0mg and Placebo at 30 Minutes	The Fridericia corrected QT interval(QTcF) 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.	baseline and 30 minutes
Change From Baseline in QTcF for MAP0004 3.0mg, Placebo, and Moxifloxacin at 2 Hours	The Fridericia corrected QT interval(QTcF) 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.	baseline and 2 hours
Change From Baseline in Heart Rate for MAP0004 3.0mg, Placebo, and Moxifloxacin at 30 Minutes and 2 Hours	The heart rate is a measure of how fast or slow the heart beats (measured in beats per minute). A negative change indicates a decrease in heart rate and a positive change indicates an increase in heart rate.	baseline, 30 minutes, and 2 hours

Collaborators and Investigators

• Sponsor: Allergan
• Collaborators: MAP Pharmaceuticals, Inc., a wholly owned subsidiary of Allergan

Publications and helpful links

General Publications

• Kori S, Kellerman DJ, Voloshko P, Haugen G. Effects of a supratherapeutic dose of investigational orally inhaled dihydroergotamine (MAP0004) on QT interval: a randomized, double-blind, active- and placebo-controlled crossover study in healthy volunteers. Clin Ther. 2012 Sep;34(9):1920-8. doi: 10.1016/j.clinthera.2012.08.001. Epub 2012 Aug 21.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): September 1, 2010
• Study Completion (ACTUAL): September 1, 2010

Study Registration Dates

• First Submitted: August 27, 2010
• First Submitted That Met QC Criteria: August 30, 2010
• First Posted (ESTIMATE): August 31, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): January 9, 2014
• Last Update Submitted That Met QC Criteria: December 9, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: MAP0004-CL-P103