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

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

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: MAP0004
* Drug: Inhaler Placebo
* Drug: Moxifloxacin
* Drug: Placebo Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 (see section 4.4) or who are sterile No known cardiac disease Normal hemoglobin values 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 Demonstrated ability to properly use the Tempo® Inhaler Subject has not donated blood in the last 56 days Exclusion Criteria: Contraindication to dihydroergotamine mesylate (DHE) History of hemiplegic or basilar migraine Family history of long QT syndrome Participation in another investigational trial during the 30 days prior to Visit 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment A, then Treatment B, then Treatment C<br>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<br>* 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol<br>Drug: Inhaler Placebo<br>* Placebo for Inhaler administered in Treatments A and C<br>Drug: Moxifloxacin<br>* 400mg encapsulated tablet administered in Treatment A as per protocol<br>* Other names: Avelox®;Drug: Placebo Capsule<br>* Placebo for Moxifloxacin administered in Treatment B and Treatment C<br>|
| Other: Treatment A, then Treatment C, then Treatment B<br>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<br>* 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol<br>Drug: Inhaler Placebo<br>* Placebo for Inhaler administered in Treatments A and C<br>Drug: Moxifloxacin<br>* 400mg encapsulated tablet administered in Treatment A as per protocol<br>* Other names: Avelox®;Drug: Placebo Capsule<br>* Placebo for Moxifloxacin administered in Treatment B and Treatment C<br>|
| Other: Treatment B, then Treatment A, then Treatment C<br>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<br>* 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol<br>Drug: Inhaler Placebo<br>* Placebo for Inhaler administered in Treatments A and C<br>Drug: Moxifloxacin<br>* 400mg encapsulated tablet administered in Treatment A as per protocol<br>* Other names: Avelox®;Drug: Placebo Capsule<br>* Placebo for Moxifloxacin administered in Treatment B and Treatment C<br>|
| Other: Treatment B, then Treatment C, then Treatment A<br>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<br>* 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol<br>Drug: Inhaler Placebo<br>* Placebo for Inhaler administered in Treatments A and C<br>Drug: Moxifloxacin<br>* 400mg encapsulated tablet administered in Treatment A as per protocol<br>* Other names: Avelox®;Drug: Placebo Capsule<br>* Placebo for Moxifloxacin administered in Treatment B and Treatment C<br>|
| Other: Treatment C, then Treatment A, then Treatment B<br>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<br>* 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol<br>Drug: Inhaler Placebo<br>* Placebo for Inhaler administered in Treatments A and C<br>Drug: Moxifloxacin<br>* 400mg encapsulated tablet administered in Treatment A as per protocol<br>* Other names: Avelox®;Drug: Placebo Capsule<br>* Placebo for Moxifloxacin administered in Treatment B and Treatment C<br>|
| Other: Treatment C, then Treatment B, then Treatment A<br>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<br>* 3.0mg orally inhaled MAP0004 administered in Treatment B as per protocol<br>Drug: Inhaler Placebo<br>* Placebo for Inhaler administered in Treatments A and C<br>Drug: Moxifloxacin<br>* 400mg encapsulated tablet administered in Treatment A as per protocol<br>* Other names: Avelox®;Drug: Placebo Capsule<br>* Placebo for Moxifloxacin administered in Treatment B and Treatment C<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers