Pharmacokinetics & Tolerability Study of MAP0004 Co-administered With Ketoconazole

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®)

Compare the DHE pharmacokinetic profiles observed following administration of:

1. MAP0004 (oral inhalation DHE)
2. MAP0004 co-administered with oral Ketoconazole
3. 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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: MAP0004; Drug: IV DHE; Drug: Ketoconazole

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Merthyr Tydfil, United Kingdom
    • Simbec Research Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: All subjects; 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; MAP0004 1.0mg via inhalation on Day 1 and Day 6 of Visit 2; Drug: IV DHE; IV DHE (Intravenous Dihydroergotamine Mesylate) administered at Visit 3; Other Names: D.H.E.45®; Drug: Ketoconazole; Ketoconazole 400 mg administered once a day on days 3-6 of Visit 2; Other Names: Nizoral®

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Kellerman D, Kori S, Forst A, Chang J, Febbraro S, Wutann L, Thomas T, Taylor G, Dodick D. Lack of drug interaction between the migraine drug MAP0004 (orally inhaled dihydroergotamine) and a CYP3A4 inhibitor in humans. Cephalalgia. 2012 Jan;32(2):150-8. doi: 10.1177/0333102411432299. Epub 2011 Dec 15.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: October 28, 2011
• First Submitted That Met QC Criteria: November 7, 2011
• First Posted (Estimate): November 9, 2011

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: Drug Drug Interaction Study in Normal Healthy Volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Ketoconazole
• Other Study ID Numbers: MAP0004-CL-P104