Epinephrine Inhalation Aerosol USP, CLINICAL STUDY-B3 FOR ASSESSMENT OF PHARMACOKINETICS

Asthma Clinical Trial

Official title:

CLINICAL STUDY-B3 FOR ASSESSMENT OF PHARMACOKINETICS, A Randomized, Evaluator-Blind, Single-Dose, Three Arm, Crossover,PK Study in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01255709
• Other study ID #: API-E004-CL-B3
• Status: Completed
• Phase: Phase 2
• First received: December 3, 2010
• Last updated: February 18, 2016
• Start date: December 2010
• Est. completion date: January 2011

Study information

• Verified date: February 2016
• 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 HFA134a propelled Metered Dose Inhaler (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.

Description:

The current study is designed to complement and expand the previous PK studies, API-E004-CL-B and API-E004-CL-B2, with emphasis on lower E004 dose strengths (at 90 and 100 mcg per inhalation), for a more thorough evaluation of the E004 PK profiles. Safety of E004 will also be evaluated, under augmented dose conditions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

• Generally healthy at screening;

• Body weight = 50 kg for men and = 45 kg for women;

• Sitting blood pressure = 135/90 mmHg;

• Demonstrating negative hIV, HBsAG and DCV-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 prior to Screening;

• 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 drug/device studies, or donated blood, in the last 30 days prior to Screening;

• Other criteria apply

Study Design

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Arm T1: Primatene Mist HFA
epinephrine inhalation aerosol, 90 mcg/inhalation, 12 inhalations over 6 minutes
• Arm T2: Primatene Mist HFA
epinephrine inhalation aerosol, 100 mcg/inhalation, 12 inhalations over 6 minutes
• Arm C: Primatene Mist (epinephrine inhalation aerosol, USP)
epinephrine inhalation aerosol, 220 mcg/inhalation, 12 inhalations over 6 minutes

Locations

Country	Name	City	State
United States	Amphastar Study Site 1	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	Pharmacokinetics including maximum concentration and area under the curve	Samples will be analyzed with an established LC/MS/MS method, with a quantitative detection limit of 0.02 ng/mL, for both epinephrine-d3 and epinephrine-h3.; Mean Maximum concentration of epinephrine (Cmax for epinephrine); Mean Area Under the Curve (AUC) for epinephrine; Time to maximum concentration (tmax) and Half life of the drug (t1/2); Epinephrine concentrations versus time	-30, 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 min postdose.	No
Secondary	Vital Signs	Systolic and Diastolic Blood pressure and heart rate	within 30 min predose, at 30, 60 and 360 min postdose	Yes
Secondary	12-lead Electrocardiogram (ECG)	12 lead ECG (Routine and QT/QTc intervals)	within 30 min pre-dose, and at 15 and 120 min post-dose	Yes
Secondary	Telemetry ECG	Telemetry recording of heart rate	within 30 min pre-dose, and during the initial 5 min post-dose	Yes