Healthy Subjects
Conditions
Brief summary
Compare the pharmacokinetics of Dihydroergotamine Mesylate (DHE) delivered by oral inhalation (MAP0004) or Intravenous (IV) DHE in smokers versus non-smokers. Identify whether there are clinically significant differences in the tolerability of MAP0004 between smokers and non-smokers.
Interventions
Sponsors
MAP Pharmaceuticals, Inc., a wholly owned subsidiary of Allergan
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Major Inclusion Criteria: 1. Able to provide written informed consent 2. Male or Female subjects 18 to 45 years old 3. Female subjects who are practicing adequate contraception or who are sterile 4. Stable cardiac status 5. Normal rhythm or arrhythmia deemed clinically insignificant on ECG Major
Exclusion criteria
1. Contraindication to dihydroergotamine mesylate (DHE) 2. Use of any excluded concomitant medications within the 10 days prior to Visit 1 (See Section 5.5) 3. History of hemiplegic or basilar migraine 4. Participation in another investigational trial during the 30 days prior to Visit 1 or during this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers Versus Non-smokers | 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 and IV DHE Administration in Smokers and Non-smokers | 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 smoking and non-smoking subjects received both MAP0004 and Intravenous (IV) Dihydroergotamine (DHE).
Participants by arm
| Arm | Count |
|---|---|
| Smokers Currently smoking at least 10 cigarettes/day for at least 1 year with a positive urinary cotinine result. | 23 |
| Non-smokers Never smoked or total exposure \<1 pack year and at least 12 months since last cigarette with a negative urinary cotinine result at screening. | 24 |
| Total | 47 |
Baseline characteristics
| Characteristic | Smokers | Non-smokers | Total |
|---|---|---|---|
| Age, Continuous | 32.91 years STANDARD_DEVIATION 7.1 | 30.71 years STANDARD_DEVIATION 8.8 | 31.79 years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 15 Participants | 16 Participants | 31 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 23 | 8 / 24 | 15 / 22 | 22 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 | 0 / 22 | 0 / 24 |
Outcome results
Primary
AUC(0-48) of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers and Non-smokers
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 Smokers | AUC(0-48) of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers and Non-smokers | 3014.968 pg*h/ml | Standard Deviation 1136.162 |
| MAP0004 1.0mg Non-smokers | AUC(0-48) of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers and Non-smokers | 4148.750 pg*h/ml | Standard Deviation 1533.861 |
| IV DHE 1.0mg Smokers | AUC(0-48) of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers and Non-smokers | 11049.027 pg*h/ml | Standard Deviation 3744.094 |
| IV DHE 1.0mg Non-smokers | AUC(0-48) of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers and Non-smokers | 11731.639 pg*h/ml | Standard Deviation 3167.828 |
Primary
Cmax of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers Versus Non-smokers
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 Smokers | Cmax of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers Versus Non-smokers | 1282.059 pg/ml | Standard Deviation 636.138 |
| MAP0004 1.0mg Non-smokers | Cmax of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers Versus Non-smokers | 2550.727 pg/ml | Standard Deviation 1297.097 |
| IV DHE 1.0mg Smokers | Cmax of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers Versus Non-smokers | 60046.128 pg/ml | Standard Deviation 49580.385 |
| IV DHE 1.0mg Non-smokers | Cmax of Dihydroergotamine After MAP0004 and IV DHE Administration in Smokers Versus Non-smokers | 48428.635 pg/ml | Standard Deviation 43894.253 |