Randomized, Placebo/Active Crossover Dose-ranging Study for Safety and Efficacy in Asthma Patients.
Information source: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Asthma
Intervention: E004 (epinephrine inhalation aerosol), 90 mcg/actuation (Drug); E004 Placebo (Drug); E004 (epinephrine inhalation aerosol), 125 mcg (Drug); E004 (epinephrine inhalation aerosol), 220 mcg (Drug); epinephrine inhalation aerosol, CFC propelled (Drug); E004 (epinephrine inhalation aerosol), 160 mcg (Drug)
Phase: Phase 1/Phase 2
Status: Terminated
Sponsored by: Amphastar Pharmaceuticals, Inc. Official(s) and/or principal investigator(s): Jim Shi, M.D., Ph.D., Study Chair, Affiliation: Amphastar Pharmaceuticals, Inc.
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.
Clinical Details
Official title: Phase 1/2 A Randomized, Double-blinded or Evaluator-blinded, Placebo and Active Controlled, Six-arm, Crossover, Single Dose, Dose-ranging Study, for Initial Evaluation of Safety and Efficacy of E004 in Asthma Patients
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: The AUC of post-dose FEV1 percentage changes (Δ%) from the Pre-dose baseline. The primary analysis of the primary endpoint is the difference of Δ% FEV1, compared between the E004 treatment arms (T1, T2, T3 and T4) and the Placebo control (Arm P).
Secondary outcome: Dose response relationship of Epinephrine HFA-MDI, analyzed using efficacy data from all E004 doses.AUC of FEV1 volume post-dose changes (Δ Volume) from the Pre-dose baseline. Time to onset of bronchodilator effect, determined by linear interpolation as the point where FEV1 first reaches 12.0 percent from the Pre-dose Baseline. The peak bronchodilator response (Fmax), defined as the maximum post-dose FEV1 percent change. The time to peak FEV1 effect (Tmax), defined as the time of Fmax. Duration of effect, calculated as the total duration of bronchodilator effects when post-dose FEV1 reaches and stays 12.0 percent above the Pre-dose Baseline. Response Rate of responders who demonstrate 12.0 percent or greater FEV1 changes from the Pre-dose baseline. Vital signs, i.e., blood pressure and heart rate,at Screening baseline and 15(±5) min post dosing for reversibility Vital signs, i.e., blood pressure (SBP/DBP) and heart rate (HR), at: Pre-dose baseline, and 15(±5) min and 360(±15) post-dose, at each Study Visit. Post-dose 20(±5) min ECG recordings (Routine and QT, QTc analysis) at each Study Visit, compared to the Screening baseline recording. Data for physical examinations, CBC, serum comprehensive metabolic panel, and urinalysis for all subjects, and urinary pregnancy test for women of child-bearing potential Monitoring of adverse drug events (ADE)
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Clinical diagnosis of intermittent, or mild-to-moderate persistent, asthma for at
least 6 months before Screening, and having used inhaled epinephrine or β-agonist(s)
for asthma control;
2. Demonstrating a baseline forced expiratory volume in 1 second (FEV1) at 50-90 percent
of predicted normal at Screening;
3. Demonstrating a 12. 0 percent or greater airway reversibility in FEV1 within 30 min
after inhaling 2 actuations of Epinephrine CFC-MDI (440 mcg Epinephrine base) at
Screening;
4. Females of child-bearing potential must be non-pregnant, non-lactating, and
practicing a clinically acceptable form of birth control;
5. Demonstration of proficiency in the use of a MDI inhaler after training;
6. Having properly consented to participate in the trial.
Exclusion Criteria:
1. A smoking history of 10 or more pack-years, or having smoked within 6 months prior to
Screening;
2. Upper respiratory tract infections within 2 wk, or lower respiratory tract infection
within 4 wk, prior to Screening;
3. Asthma exacerbations that required emergency care or hospitalized treatment, within 4
wk prior to Screening;
4. Any current or recent respiratory conditions that, per investigator discretion, might
significantly affect pharmacodynamic response to the study drugs, including cystic
fibrosis, bronchiectasis, tuberculosis, emphysema, and other significant respiratory
diseases besides asthma;
5. Concurrent clinically significant cardiovascular, hematological, renal, neurologic,
hepatic, endocrine (including diabetes), psychiatric, neoplastic or other illnesses
that in the opinion of the investigator could impact on the conduct, safety and
evaluation of the study;
6. Known intolerance or hypersensitivity to any of the study MDI ingredients (i. e.,
Epinephrine, HFA-134a, CFC-12, CFC-114, polysorbate-80, ethanol, thymol, nitric acid
and ascorbic acid);
7. Use of prohibited drugs or failure to observe the drug washout restrictions;
8. Having been on other investigational drug/device studies in the last 30 days prior to
Screening.
Locations and Contacts
Additional Information
Related 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. 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. 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. 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 Armstrong Pharmaceuticals: Package Insert of Epinephrine Inhalation Aerosol USP, a CFC-MDI, current as of 2008 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 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. 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: 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. Global Initiative for Asthma (GINA): Pocket guide for asthma management and prevention,
Starting date: December 2009
Last updated: July 11, 2013
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