Assessment and Evaluation of Pharmacokinetic Profile of E004 in Healthy Adults
This study examines the pharmacokinetic profile of Armstrong's proposed Epinephrine Inhalation Aerosol USP, an HFA-MDI (E004), using a stable isotope deuterium-labeled epinephrine (epinephrine-d3) to differentiate the administered drug from the endogenous epinephrine, in healthy male and female adult volunteers. The current study is designed to complement an earlier PK study, API-E004-CL-B, for a more thorough evaluation of the E004 PK. Safety of E004 will also be evaluated.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Assessment and Evaluation of Pharmacokinetic Profile of E004 in Healthy Adults (A Randomized, Evaluator-Blind, Single-Dose, Two Arm, Crossover, PK Study in Healthy Volunteers)|
- Calculation and Comparison of relative Bioavailability of Epinephrine [ Time Frame: up to 30 min predose and at 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 minutes postdose ] [ Designated as safety issue: No ]Blood PK samples will be collected at each visit for both study arms, then the Area Under the Curve (s) will be calculated for both arms and compared to give relative bioavailability
- Vital Signs [ Time Frame: up to 30 min predose and at 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 minutes postdose ] [ Designated as safety issue: Yes ]Vital signs (SBP/DBP, blood pressure and heart rate) will be documented and summarized
- 12-lead ECG (Routine and QT/QTc analysis) [ Time Frame: up to 30 min predose and at 5, 10, 15, 20, 30, 60, 120, and 360 minutes postdose ] [ Designated as safety issue: Yes ]A 12-lead ECG (Routine and QT/QTc analysis) will be documented.
- Physical Examinations [ Time Frame: up to 30 min predose and after 360 min post last dose ] [ Designated as safety issue: Yes ]Physical examinations will be documented at screening and end of study
- Lab tests [ Time Frame: up to 30 min predose ] [ Designated as safety issue: Yes ]Lab tests, including CBC, serum comprehensive metabolic panel, urinalysis, and drug/alcohol screens for all subjects and urinary pregnancy test for women of child-bearing potential will be performed and documented
|Study Start Date:||November 2012|
|Estimated Study Completion Date:||December 2012|
|Estimated Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: Arm T - Epinephrine Inhalation Aerosol, HFA
Experimental arm utilizing Epinephrine HFA-MDI (E004)
Drug: Arm T
Epinephrine Inhalation Aerosol HFA, Single dose 125 mcg, 1 inhalation
Active Comparator: Arm C - Epinephrine Inhalation Aerosol - CFC
Active comparator arm utilizing Epinephrine CFC-MDI
Drug: Arm C -
Epinephrine Inhalation Aerosol - CFC, Single dose 220 mcg, 1 inhalation
This study is a randomized, evaluator-blind, single dose, two-arm, crossover, PK study, to be conducted in ~18 healthy, male and female, adult volunteers. PK will be studied using E004-d3 at 125 mcg per inhalation (Arm T). A previously marketed Epinephrine CFC-MDI, labeled "For Investigational Use Only" will be used as a Reference Control (Arm C).
The main features of the study design are:
(1) All candidates must be screened and must satisfy all enrollment criteria. All enrolled subjects will participate in two Study Visits, corresponding to two randomized treatments. Each Study Visit consists of a pre-dose baseline assessment and a post-dose evaluation for 6 hours.
(2) It is important to minimize physical and psychological disturbances to the endogenous epinephrine concentrations in the study subjects, before and during the study visits. All subjects must maintain a reclining or recumbent resting position during the entire Study Visit, with physical activities restricted to a minimum necessity for bathroom trips and study activities. Caffeine-containing (including de-caffeinated) foods or beverages are prohibited. Physical exercise, unnecessary physical activities, and video games are prohibited throughout the study visit.
(3)At the Screening Visit and the beginning of each Study Visit, each subject will be trained on the correct self-administration of MDI, using a simulation MDI unit that contains no active drug. The following two randomized treatments will be self-administered at two Study Visits:
Treatment T: Two (2) inhalations of E004-d3 (125 mcg/inhalation), totaling 250 mcg of epinephrine-d3;
Treatment C: Two (2) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation, totaling 440 mcg of epinephrine base equivalent).
(4) PK blood samples will be taken from a vein in a hand or arm via an indwelling anticoagulated IV catheter, or by venipunctures, at scheduled time points of predose baseline (within 30 minutes of dosing), and at 2±1, 5±1, 7.5±1, 10±1, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 minutes postdose. The total volume of blood taken per subject shall not exceed 500 mL in any 30-day period. Study visit schedule may be adjusted to avoid overdrawing blood in any 30-day period.
(5) At each PK sampling point, blood samples (~ 5mL), will be collected in ice-chilled potassium-EDTA sample tubes, each containing pre-added 1% (V:V) of a 1.0 M sodium metabisulfite solution as an antioxidant. Sample tubes will be labeled with a sample ID# (consisting of subject ID#, Study Visit#, and sample#). The sample tubes will be kept on ice or refrigerated, and will be centrifuged within 60 minutes of collection. The harvested plasma from each sample tube will be transferred to, and stored in, 2 storage tubes, respectively, and frozen at NMT -20 degrees C until analysis.
(6) PK samples will be analyzed with an established LC/MS/MS method, with a quantitative detection limit of 5 pg/mL, for both epinephrine-d3 (MW=186) and epinephrine (MW=183).
(7) 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 at the end of, or within 7 days after, Study Visit-2.
|Contact: Vladimir Evilevitch, M.D.||(909)984-9484 ext firstname.lastname@example.org|
|United States, California|
|West Coast Clinical Trials, LLC||Recruiting|
|Cypress, California, United States, 90630|
|Contact: Vladimir Evilevitch, M.D. 909-980-9484 ext 2030 email@example.com|
|Principal Investigator: Apinya B. Vutikullird, DO|
|Study Director:||Vladimir Evilevitch, M.D.||Amphastar Pharmaceuticals, Inc.|