Pharmacokinetics & Tolerability Study of MAP0004 Co-administered With Ketoconazole

Study Overview
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Brief Summary
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Compare the DHE pharmacokinetic profiles observed following administration of: MAP0004 (oral inhalation DHE) MAP0004 co-administered with oral Ketoconazole Intravenous (IV) DHE (D.H.E.45®, the approved reference therapy) Compare the tolerability of MAP0004, IV DHE, and MAP0004 with co-administration of Ketoconazole.

Official Title
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A Phase I Evaluation of the Effect of Ketoconazole on the Pharmacokinetics and Safety of Dihydroergotamine Mesylate (DHE) Delivered by Oral Inhalation (MAP0004) in Healthy Volunteers Compared to DHE Delivered Intravenously (DHE 45®)

Conditions
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Healthy

Intervention / Treatment
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* Drug: MAP0004
* Drug: IV DHE
* Drug: Ketoconazole


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Able to provide written Informed Consent Male or Female subjects 18 to 45 years old Female subjects who are practicing adequate contraception or who are sterile Stable cardiac status Normal rhythm or arrhythmia deemed clinically insignificant on ECG Exclusion Criteria: 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 12 weeks prior to Visit 1 or during this trial

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: All subjects<br>Subjects received MAP0004 on Day 1 of Visit 2, Ketoconazole on Days 3 through 6 of Visit 2, and MAP0004 again on Day 6 of Visit 2. Subjects then returned for Visit 3, 7-11 days from the end of Visit 2. At Visit 3 subjects received 1.0 mg IV DHE (Intravenous Dihydroergotamine Mesylate). | Drug: MAP0004<br>* MAP0004 1.0mg via inhalation on Day 1 and Day 6 of Visit 2<br>Drug: IV DHE<br>* IV DHE (Intravenous Dihydroergotamine Mesylate) administered at Visit 3<br>* Other names: D.H.E.45®;Drug: Ketoconazole<br>* Ketoconazole 400 mg administered once a day on days 3-6 of Visit 2<br>* Other names: Nizoral®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration | The maximum concentration (Cmax) is the highest concentration of a drug measured in the plasma. Plasma is the clear portion of the blood. The Cmax of Dihydroergotamine is reported in picograms per milliliter (pg/ml). | 48 hours | 
| AUC(0-48) of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration | The AUC(0-48) is the area under the plot of plasma concentration of drug against time after drug administration. Dihydroergotamine AUC(0-48) is reported in picograms times hour per milliliter (pg*h/ml). | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Drug Interaction Study in Normal Healthy Volunteers