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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01188577
Other study ID # API-E004-CL-B2
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received August 24, 2010
Last updated October 21, 2014
Start date August 2010
Est. completion date January 2011

Study information

Verified date October 2014
Source Amphastar Pharmaceuticals, Inc.
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

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 for a more thorough evaluation of the E004 Pharmacokinetics. Safety of E004 will also be evaluated, under augmented dose conditions.


Description:

E004 is formulated with epinephrine free base as the active ingredient, and hydrofluoroalkane (HFA-134a) as the propellant.

In order to differentiate the inhaled epinephrine from the fluctuating background of endogenous epinephrine 1, a stable-isotope deuterium (2H) labeled epinephrine (epinephrine-d3) preparation will be used to formulate E004 inhalers, denoted as E004-d3. PK of E004 at 125 mcg of epinephrine-d3 per inhalation, will be compared to that of the currently marketed, non-labeled, Epinephrine-CFC MDI as the Reference Control (220 mcg per 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 currently marketed, non-labeled, Epinephrine CFC-MDI will be used as a Reference Control (Arm C).


Recruitment information / eligibility

Status Completed
Enrollment 23
Est. completion date January 2011
Est. primary completion date September 2010
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years to 30 Years
Eligibility Inclusion Criteria:

- Generally healthy at screening;

- No clinically significant respiratory, cardiovascular and other systemic or organic illnesses;

- Body weight = 50 kg for men and = 45 kg for women,

- Sitting blood pressure = 135/90 mm Hg;

- Demonstrating negative HIV, HBsAg and HCV-Ab screen tests;

- Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;

- Properly consented

- Other criteria apply

Exclusion Criteria:

- A smoking history of =10 pack-years, or having smoked within 6 months;

- Upper respiratory tract infections within 2 wk, or lower respiratory tract infection within 4 wk, prior to Screening;

- Any current or recent respiratory conditions that might significantly affect pharmacodynamic response to the study drugs;

- Known intolerance or hypersensitivity to the study MDI ingredients;

- Having been on other investigational studies, or donated blood, in the last 30 days;

- Other Criteria Apply

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment


Intervention

Drug:
Epinephrine Inhalation Aerosol, HFA
10 inhalations of epinephrine inhalation aerosol, 125 mcg/inhalation
Epinephrine Inhalation Aerosol
Epinephrine Inhalation Aerosol, 220 mcg/ inhalation, 10 inhalations

Locations

Country Name City State
United States Armstrong Study Site One Cypress California

Sponsors (1)

Lead Sponsor Collaborator
Amphastar Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (8)

Bondesson E, Friberg K, Soliman S, Löfdahl CG. Safety and efficacy of a high cumulative dose of salbutamol inhaled via Turbuhaler or via a pressurized metered-dose inhaler in patients with asthma. Respir Med. 1998 Feb;92(2):325-30. — View Citation

Cripps A, Riebe M, Schulze M, Woodhouse R. Pharmaceutical transition to non-CFC pressurized metered dose inhalers. Respir Med. 2000 Jun;94 Suppl B:S3-9. — View Citation

Dickinson BD, Altman RD, Deitchman SD, Champion HC. Safety of over-the-counter inhalers for asthma: report of the council on scientific affairs. Chest. 2000 Aug;118(2):522-6. — View Citation

Hendeles L, Marshik PL, Ahrens R, Kifle Y, Shuster J. Response to nonprescription epinephrine inhaler during nocturnal asthma. Ann Allergy Asthma Immunol. 2005 Dec;95(6):530-4. — View Citation

Kushner DJ, Baker A, Dunstall TG. Pharmacological uses and perspectives of heavy water and deuterated compounds. Can J Physiol Pharmacol. 1999 Feb;77(2):79-88. Review. — View Citation

Pinnas JL, Schachtel BP, Chen TM, Roseberry HR, Thoden WR. Inhaled epinephrine and oral theophylline-ephedrine in the treatment of asthma. J Clin Pharmacol. 1991 Mar;31(3):243-7. — View Citation

Simons FE, Gu X, Johnston LM, Simons KJ. Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis? Pediatrics. 2000 Nov;106(5):1040-4. — View Citation

Warren JB, Doble N, Dalton N, Ewan PW. Systemic absorption of inhaled epinephrine. Clin Pharmacol Ther. 1986 Dec;40(6):673-8. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Baseline Concentration (C0) of Total Epinephrine Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at Baseline (prior to dosing) in each treatment period following a specified washout period (3-14 days), and were analyzed using an established analysis method. Baseline concentration (C0) is the concentration of epinephrine measured in the plasma at this time point. 0 to 30 minutes prior to dosing No
Primary Peak Concentration (Cmax) of Total Epinephrine From Time Zero to 6 Hours Post-dose Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Peak (maximum) concentration (Cmax) is the highest concentration of epinephrine measured in plasma during the treatment period. Pre-dose to 6 hours post-dose No
Primary Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) for Total Epinephrine Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Area under the curve from time zero to 6 hours post-dose (AUC[0-6]) was calculated using the trapezoidal rule. Pre-dose to 6 hours post-dose No
Primary Time to Reach Peak Concentration (Tmax) for Total Epinephrine Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Tmax is the amount of time it takes for epinephrine to reach peak concentration in plasma during the treatment period. Pre-dose to 6 hours post-dose No
Primary Half-life (t1/2) of Total Epinephrine Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Half-life (t1/2) is the amount of time it takes for epinephrine to decrease to half the peak concentration in plasma during the treatment period. Pre-dose to 6 hours post-dose No
Primary Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Pre-dose to 6 hours post-dose No
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