Healthy
Conditions
Keywords
Drug Drug Interaction Study in Normal Healthy Volunteers
Brief summary
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.
Interventions
Sponsors
MAP Pharmaceuticals, Inc., a wholly owned subsidiary of Allergan
Allergan
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration | 48 hours | 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). |
| AUC(0-48) of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration | 48 hours | 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). |
Countries
United Kingdom
Participant flow
Pre-assignment details
All 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 Intravenous (IV) Dihydroergotamine Mesylate (DHE).
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All subjects that were enrolled in the study. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 29.58 years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 24 | 7 / 24 | 11 / 22 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 22 |
Outcome results
Primary
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).
Time frame: 48 hours
Population: Patients with available data at specified time points are included in the analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MAP0004 1.0mg | AUC(0-48) of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration | 3484.725 pg*h/ml | Standard Deviation 1221.423 |
| MAP0004 1.0mg + Ketoconazole | AUC(0-48) of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration | 4070.611 pg*h/ml | Standard Deviation 1628.973 |
| IV DHE 1.0mg | AUC(0-48) of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration | 9229.171 pg*h/ml | Standard Deviation 3130.093 |
Primary
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).
Time frame: 48 hours
Population: Patients with available data at specified time points are included in the analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MAP0004 1.0mg | Cmax of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration | 2582.507 pg/ml | Standard Deviation 1137.829 |
| MAP0004 1.0mg + Ketoconazole | Cmax of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration | 2495.100 pg/ml | Standard Deviation 1130.85 |
| IV DHE 1.0mg | Cmax of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration | 27771.234 pg/ml | Standard Deviation 36191.528 |