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

• ClinicalTrials.gov Identifier: NCT01255709
• Recruitment Status: Completed
• First Posted: December 7, 2010
• Last Update Posted: March 17, 2016
• Sponsor: Amphastar Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Amphastar Pharmaceuticals, Inc.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: Arm T1: Primatene Mist HFA; Drug: Arm T2: Primatene Mist HFA; Drug: Arm C: Primatene Mist (epinephrine inhalation aerosol, USP)	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: CLINICAL STUDY-B3 FOR ASSESSMENT OF PHARMACOKINETICS, A Randomized, Evaluator-Blind, Single-Dose, Three Arm, Crossover,PK Study in Healthy Volunteers
• Study Start Date: December 2010
• Actual Primary Completion Date: January 2011
• Actual Study Completion Date: January 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm T1 Primatene Mist HFA; epinephrine inhalation aerosol, 90 mcg/inhalation, 12 inhalations over 6 minutes	Drug: Arm T1: Primatene Mist HFA; epinephrine inhalation aerosol, 90 mcg/inhalation, 12 inhalations over 6 minutes; Other Name: epinephrine inhalation aerosol
Active Comparator: Arm C Primatene Mist; epinephrine inhalation aerosol, 220 mcg/inhalation, 12 inhalations over 6 minutes	Drug: Arm C: Primatene Mist (epinephrine inhalation aerosol, USP); epinephrine inhalation aerosol, 220 mcg/inhalation, 12 inhalations over 6 minutes; Other Name: epinephrine inhalation aerosol
Experimental: Arm T2 Primatene Mist HFA; epinephrine inhalation aerosol, 100 mcg/inhalation, 12 inhalations over 6 minutes	Drug: Arm T2: Primatene Mist HFA; epinephrine inhalation aerosol, 100 mcg/inhalation, 12 inhalations over 6 minutes; Other Name: epinephrine inhalation aerosol

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetics including maximum concentration and area under the curve [ Time Frame: -30, 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 min postdose. ]

   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

Secondary Outcome Measures :

1. Vital Signs [ Time Frame: within 30 min predose, at 30, 60 and 360 min postdose ]
   Systolic and Diastolic Blood pressure and heart rate
2. 12-lead Electrocardiogram (ECG) [ Time Frame: within 30 min pre-dose, and at 15 and 120 min post-dose ]
   12 lead ECG (Routine and QT/QTc intervals)
3. Telemetry ECG [ Time Frame: within 30 min pre-dose, and during the initial 5 min post-dose ]
   Telemetry recording of heart rate

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 30 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, California

Amphastar Study Site 1

Cypress, California, United States, 90630

Sponsors and Collaborators

Amphastar Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Director; Amphastar Pharmaceuticals, Inc.

More Information

Publications:

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.

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.

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

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.

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.

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.

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.

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.

• Responsible Party: Amphastar Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01255709
• Other Study ID Numbers: API-E004-CL-B3
• First Posted: December 7, 2010
• Last Update Posted: March 17, 2016
• Last Verified: February 2016

Keywords provided by Amphastar Pharmaceuticals, Inc.:

Asthma; shortness of breath; wheezing

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Epinephrine; Racepinephrine; Epinephryl borate; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Adrenergic beta-Agonists; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Asthmatic Agents; Respiratory System Agents; Mydriatics; Sympathomimetics; Vasoconstrictor Agents