Clinical trial NCT01143051: Pharmacokinetics (PK) Study of Epinephrine Inhalation Aerosol in Healthy Volunteers
Official title: Phase I/II Study Epinephrine Inhalation Aerosol USP, an HFA-MDI Clinical Study-B for Assessment of Pharmacokinetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Asthma
Keywords: Asthma
Pharmacokinetics
Epinephrine
Bronchodilator
metered dose inhaler
Lead sponsor: Amphastar Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2010-06-14
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study examines the pharmacokinetic profile of Armstrong's proposed Epinephrine Inhalation Aerosol USP, an HFA-MDI (E004), in healthy male and female adult volunteers. Safety of E004 will also be evaluated, under augmented dose conditions.

Detailed description: This study is a randomized, evaluator-blind, single dose, three-arm, crossover, PK study, to be conducted in \~18 healthy, male and female, adult volunteers. PK will be studied at two dose strengths (Arm T1 and Arm T2). A currently marketed, non-labeled, Epinephrine CFC-MDI will be used as a Reference Control (Arm C).

* At the Screening Visit and the beginning of each Study Visit, each subject will be trained on the correct self-administration of MDI. The following three randomized treatments will be self-administered, at three Study Visits:

  * Treatment T1: Ten (10) inhalations of the low dose E004(125 mcg/inhalation), totaling 1.25 mg of epinephrine;
  * Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine;
  * Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation, totaling 2.2 mg of epinephrine base equivalent).
* PK blood samples will be taken from a vein at scheduled time points.
* Safety parameters and adverse drug events, if any, will be monitored and documented at each study visit. An End-of-Study (EOS) safety evaluation will be conducted.

Eligibility criteria: Inclusion Criteria:

* Generally healthy, male and female adults, 18-30 yrs of age at Screening;
* Having no clinically significant respiratory, cardiovascular and other systemic or organic illnesses, per investigator discretion;
* Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;
* Having properly consented and satisfied all other inclusion/exclusion criteria as required for this protocol.
* Other criteria apply.

Exclusion Criteria:

* A recent or significant smoking history;
* Use of prohibited drugs or failure to observe the drug washout restrictions;
* Having been on other investigational drug/device studies in the last 30 days prior to Screening.
* Other criteria apply

Primary outcomes:
measure: Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine
timeFrame: 0 to 30 minutes prior to dosing
measure: Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6])
timeFrame: Pre-dose to 6 hours post-dose
measure: Peak Concentration (Cmax) for Total Epinephrine From Time Zero to 6 Hours Post-dose
timeFrame: Pre-dose to 6 hours post-dose
measure: Time to Reach Peak Concentration (Tmax) for Total Epinephrine
timeFrame: Pre-dose to 6 hours post-dose
measure: Half-life (t1/2) for Total Epinephrine
timeFrame: Pre-dose to 6 hours post-dose
measure: Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
timeFrame: Pre-dose to 6 hours post-dose
Secondary outcomes:
measure: Vital Signs: Systolic Blood Pressure (SBP)
timeFrame: Pre-dose (baseline) to 360 minutes post-dose
measure: Vital Signs: Diastolic Blood Pressure (DBP)
timeFrame: Pre-dose (baseline) to 360 minutes post-dose
measure: Vital Signs: Heart Rate (HR)
timeFrame: Pre-dose (baseline) to 360 minutes post-dose
measure: ECG: QT Interval
timeFrame: Pre-dose (baseline) to 360 minutes post-dose
measure: ECG: QTc Interval
timeFrame: Pre-dose (baseline) to 360 minutes post-dose
measure: Serum Glucose Levels
timeFrame: Pre-dose (baseline) to 360 minutes post-dose
measure: Serum Potassium Levels
timeFrame: Pre-dose (baseline) to 360 minutes post-dose
measure: Hand Tremor Scores
timeFrame: Pre-dose (baseline) to 360 minutes post-dose
measure: Number of Subjects With Significant Changes in Physical Examination
timeFrame: Approximately 6 weeks
measure: Number of Subjects With Significant Changes in Laboratory Tests
timeFrame: Approximately 6 weeks
Other outcomes:
Locations:
city: Cypress
country: United States
facility: Amphastar Location 1
state: California
Study officials:
affiliation: Amphastar Pharmaceuticals, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: