Randomized, Placebo/Active Crossover Dose-ranging Study for Safety and Efficacy in Asthma Patients.

Summary

The main objective of this study is to evaluate the efficacy and safety of the Armstrong's Epinephrine HFA-MDI (E004) formulation, in comparison to the Placebo (Placebo-HFA) and an Active Control (Epinephrine CFC-MDI), and to identify the optimum E004 dose strength(s) for the ensuing pivotal clinical trials. The study will be conducted in adult patients who have intermittent, or mild-to-moderate persistent, asthma, but are otherwise healthy. The bronchodilatory efficacy of E004, is evaluated in terms of post-dose area under the curves (AUC) of FEV1 changes (% and volumes), from the pre-dose baseline values, in comparison to the Placebo Control and the Active Control.

Timeline

Start

2009-12

Primary completion

2009-12

Completion

2009-12

Publications

• Background 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. doi: 10.1002/j.1552-4604.1991.tb04969.x.
• Background 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. doi: 10.1016/S1081-1206(10)61014-9.
• Background Warren JB, Doble N, Dalton N, Ewan PW. Systemic absorption of inhaled epinephrine. Clin Pharmacol Ther. 1986 Dec;40(6):673-8. doi: 10.1038/clpt.1986.243.
• Background 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.
• Background 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. doi: 10.1378/chest.118.2.522.
• Background 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. doi: 10.1542/peds.106.5.1040.
• Background Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.
• Background Crapo RO, Morris AH, Clayton PD, Nixon CR. Lung volumes in healthy nonsmoking adults. Bull Eur Physiopathol Respir. 1982 May-Jun;18(3):419-25.
• Background Dauphinee B, Tashkin DP, et al: Placebo-controlled evaluation of the speed of onset of epinephrine metered-dose aerosol (Primatene Mist) in mild to moderate asthmatics. Am J Respir Crit Care Med, 149:A204, 1994
• Background Armstrong Pharmaceuticals: Package Insert of Epinephrine Inhalation Aerosol USP, a CFC-MDI, current as of 2008
• Background Westfall TC, Westfall DP: Adrenergic agonists and antagonists, in Brunton LL, Lazo JS, Parker KL (eds): Goodman & Gilman's Ther Pharmacological Basis of Therapeitucs, 11th Ed. P237-296, 1986
• Background Montreal Protocol on substances that deplete the ozone layer, Montreal, Spet 1987; Adjusted and/or amended in London 1990; Copenhagen 1992; Vienna 1995; Montreal 1997 and Beijing 1999.
• Background NHLBI/NAEPP (National Heart, Lund and Blood Institute; Natuinak /asthma Education and Prevention Program) Expert Panel Report 3 (2007): Guidelines for the diagnosis and management of asthma, Section 3, Component 1, Figure 3-4C:
• Background Wyeth Consumer Healthcare: 2005N-0374, Use of ozone-depleting substances: Essential-use determination of over-the-counter (OTC) epinephrine metered dose inhalers. Submitted to teh Nonprescription Drugs and Pulmonary-Allergy Drugs Advisory Committees. Dec 2005.
• Background Global Initiative for Asthma (GINA): Pocket guide for asthma management and prevention,
• Kerwin EM, Tashkin DP, Murphy TR, Bensch GW, Marrs T, Luo MZ, Zhang JY. A Dose-Ranging Study of Epinephrine Hydrofluroalkane Metered-Dose Inhaler (Primatene(R) MIST) in Subjects with Intermittent or Mild-to-Moderate Persistent Asthma. J Aerosol Med Pulm Drug Deliv. 2020 Aug;33(4):186-193. doi: 10.1089/jamp.2019.1558. Epub 2020 Mar 6.

Drugs

Indications