Migraine
Conditions
Keywords
Migraine, Prochlorperazine aerosol
Brief summary
The objective of this study was to evaluate the tolerability, safety, and pharmacokinetics of inhaled prochlorperazine
Detailed description
The objective of this study was to evaluate the tolerability, safety, and pharmacokinetics of a single, inhaled dose of prochlorperazine (PCZ), administered as 1 or 2 puffs in healthy young volunteers.
Interventions
DRUGProchlorperazine 0.5 mg IV over 5 sec
IV Prochlorperazine for bioavailability
DRUGInhaled prochlorperazine 0.625 mg
Inhaled Staccato Prochlorperazine 0.625 mg
DRUGInhaled prochlorperazine 1.25 mg
Inhaled Staccato Prochlorperazine 1.25 mg
DRUGInhaled prochlorperazine 2.5 mg
Inhaled Staccato Prochlorperazine 2.5 mg
InhaledStaccato Prochlorperazine 5 mg
InhaledStaccato Prochlorperazine 10 mg
DRUGInhaled placebo
Inhaled Staccato Placebo (0 mg)
DRUGProchlorperazine 10 mg IV over 5 sec
Prochlorperazine 10 mg IV over 5 sec for patient qualification
Sponsors
Alexza Pharmaceuticals, Inc.
PPD Development, LP
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Stage 2 was a double-blind, placebo-controlled, 4 step dose-escalation trial
Intervention model description
Stage 1: open-label, single-dose stage with 3 treatment periods divided into 2 phases Stage 2: double-blind, placebo-controlled, dose-escalation treatment period
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects will be male or female subjects between the ages 18 to 45 years, inclusive in good general health as determined by medical history, physical examination, 12-lead ECG, spirometry, blood chemistry profile, hematology, urinalysis and in the opinion of the Principal Investigator.
Exclusion criteria
* Subjects with a known history of allergy or intolerance to phenothiazines or related drugs or who have any disease, by history, physical examination, or laboratory abnormalities that in the investigator's opinion, would present undue risk to the subject, or may confound the interpretation of study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Peak (Tmax) | 24 hours | Time from dose to peak prochlorperazine concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Bioavailability of Inhaled Prochlorperazine | 24 hours | Absolute bioavailability of inhaled prochlorperazine via AUC infinity |
| Dose Proportionality of Inhaled Prochlorperazine by Power Analysis | 24 hours | Dose proportionality by power analysis examines the linear regression of the log-AUC versus log-Dose on a by-patient basis across all doses administered. The slope and 90% confidence interval (CI) provide a clear, quantitative (best practices) assessment of the relationship of drug delivered to dose administered. The units on such analyses are generally those of slope (rise over run), with 1.000 being perfect. Although any positive slope might be considered clinically useful, a 90% CI within the criteria of 0.800-1.250 may be considered a delivery system which is as good as it gets. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Qualification & Crossover, Inhaled Prochlorperazine vs IV Prochlorperazine 10 mg IV over 2 min qualification
Prochlorperazine 0.5 mg IV over 5 sec crossover Inhaled prochlorperazine 0.625 mg
ALL SUBJECTS RECEIVED ALL 3 TREATMENTS | 14 |
| Inhaled Prochlorperazine 1.25 mg Inhaled Staccato prochlorperazine 1.25 mg
Inhaled prochlorperazine 1.25 mg: Inhaled Staccato Prochlorperazine 1.25 mg | 8 |
| Inhaled Prochlorperazine 2.5 mg Inhaled Staccato prochlorperazine 2.5 mg
Inhaled prochlorperazine 2.5 mg: Inhaled Staccato Prochlorperazine 2.5 mg | 8 |
| Inhaled Prochlorperazine 5 mg Inhaled Staccato prochlorperazine 5 mg
Inhaled prochlorperazine 5 mg: InhaledStaccato Prochlorperazine 5 mg | 8 |
| Inhaled Prochlorperazine 10 mg Inhaled Staccato prochlorperazine 10 mg
Inhaled prochlorperazine 10 mg: InhaledStaccato Prochlorperazine 10 mg | 8 |
| Inhaled Placebo inhaled Staccato Placebo (0 mg)
Inhaled placebo: Inhaled Staccato Placebo (0 mg) | 8 |
| Total | 54 |
Baseline characteristics
| Characteristic | Inhaled Prochlorperazine 1.25 mg | Inhaled Prochlorperazine 2.5 mg | Inhaled Prochlorperazine 5 mg | Qualification & Crossover, Inhaled Prochlorperazine vs IV | Inhaled Prochlorperazine 10 mg | Inhaled Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 8 Participants | 14 Participants | 8 Participants | 8 Participants | 54 Participants |
| Age, Continuous | 25.1 years STANDARD_DEVIATION 3.44 | 25 years STANDARD_DEVIATION 4.57 | 26.4 years STANDARD_DEVIATION 8.94 | 29.4 years STANDARD_DEVIATION 7.86 | 28.8 years STANDARD_DEVIATION 10.2 | 23.5 years STANDARD_DEVIATION 7.03 | 25.8 years STANDARD_DEVIATION 7.09 |
| Region of Enrollment United States | 8 participants | 8 participants | 8 participants | 14 participants | 8 participants | 8 participants | 54 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 4 Participants | 6 Participants | 4 Participants | 4 Participants | 26 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 8 Participants | 4 Participants | 4 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 6 / 14 | 0 / 8 | 0 / 8 | 5 / 8 | 3 / 8 | 0 / 8 | 4 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 14 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Time to Peak (Tmax)
Time from dose to peak prochlorperazine concentration
Time frame: 24 hours
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.5 mg 5 Sec IV | Time to Peak (Tmax) | 0.042 hours |
| 0.625 mg Inhaled Prochlorperazine | Time to Peak (Tmax) | 0.033 hours |
| 1.25 mg Inhaled | Time to Peak (Tmax) | 0.025 hours |
| 2.5 mg Inhaled | Time to Peak (Tmax) | 0.033 hours |
| 5 mg Inhaled | Time to Peak (Tmax) | 0.040 hours |
| 10 mg Inhaled | Time to Peak (Tmax) | 0.033 hours |
Secondary
Absolute Bioavailability of Inhaled Prochlorperazine
Absolute bioavailability of inhaled prochlorperazine via AUC infinity
Time frame: 24 hours
Population: Bioavailability crossover subjects, n=8
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| 0.5 mg 5 Sec IV | Absolute Bioavailability of Inhaled Prochlorperazine | 0.98 Fraction absorbed |
Secondary
Dose Proportionality of Inhaled Prochlorperazine by Power Analysis
Dose proportionality by power analysis examines the linear regression of the log-AUC versus log-Dose on a by-patient basis across all doses administered. The slope and 90% confidence interval (CI) provide a clear, quantitative (best practices) assessment of the relationship of drug delivered to dose administered. The units on such analyses are generally those of slope (rise over run), with 1.000 being perfect. Although any positive slope might be considered clinically useful, a 90% CI within the criteria of 0.800-1.250 may be considered a delivery system which is as good as it gets.
Time frame: 24 hours
Population: Pharmacokinetic Population, n=40
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| 0.5 mg 5 Sec IV | Dose Proportionality of Inhaled Prochlorperazine by Power Analysis | 1.089 Slope of Power Regression |