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E004-C2 is a continuation of E004-C for safety evaluations with additional 3 months to be able to assess the 6-month safety profile for E004 (epinephrine inhalation) versus placebo in a double-blinded manner.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm T | Experimental | Arm T is the experimental treatment arm consisting of 2 x 125 mcg/inhalations of epinephrine inhalation, QID, with 4-6 hr intervals |
|
| Arm P | Placebo Comparator | Arm P is a placebo comparator consisting of 2× 0 mcg of placebo inhalations, QID, with 4-6 hr intervals |
|
| Arm A | Active Comparator | Arm A is an active comparator, Primatene Mist, consisting of 2× 220 mcg/inhalation, QID, with 4-6 hr intervals |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | 0 mcg/inhalation, 2 inhalations QID |
| |
| Primatene Mist |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events | Recording of all adverse events experienced during the course of the study | up to 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in 12 lead ECG including QT/QTc analysis | A 12-lead ECG (routine and QT/QTc) will be measured and recorded, provided that dosing of study drug has been performed greater than 1 hour prior to conducting the measurements. | Study visit 4, 8 and 12, greater than one hour after last dose |
| Asthma Exacerbations |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Safety Monitor | Amphastar Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amphastar Site 0006 | Costa Mesa | California | 92626 | United States | ||
| Amphastar Site 0005 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 2019665 | 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. | |
| 16400891 | 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. |
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| Drug |
220 mcg/inhalation, 2 inhalations QID |
|
| Epinephrine inhalation | Drug | 125 mcg/inhalation, 2 inhalations QID |
|
Review use of resuce inhaler for treatment of asthma exacrbations occuring between doses of study medication. |
| up to 12 weeks |
| Los Angeles |
| California |
| 90048 |
| United States |
| Amphastar Site 0004 | Orange | California | 92868 | United States |
| Amphastar Site 0001 | San Jose | California | 95117 | United States |
| Amphastar Site 0003 | Stockton | California | 95207 | United States |
| Amphastar Site 0008 | Denver | Colorado | 80230 | United States |
| Amphastar Site 0009 | Wheat Ridge | Colorado | 80033 | United States |
| Amphastar Site 0011 | Iowa City | Iowa | 52240 | United States |
| Amphastar Site 0013 | North Dartmouth | Massachusetts | 02747 | United States |
| Amphastar Site 0014 | Minneapolis | Minnesota | 55402 | United States |
| Amphastar Site 0015 | Plymouth | Minnesota | 55441 | United States |
| Amphastar Site 0016 | St Louis | Missouri | 63141 | United States |
| Amphastar Site 0017 | Bozeman | Montana | 59718 | United States |
| Amphastar Site 0019 | Bellevue | Nebraska | 68123 | United States |
| Amphastar Site 0020 | Skillman | New Jersey | 08558 | United States |
| Amphastar Site 0018 | Raleigh | North Carolina | 27607 | United States |
| Amphastar Site 0021 | Cincinnati | Ohio | 45242 | United States |
| Amphastar Site 0024 | Ashland | Oregon | 97520 | United States |
| Amphastar Site 0022 | Eugene | Oregon | 97401 | United States |
| Amphastar Site 0023 | Lake Oswego | Oregon | 97035 | United States |
| Amphastar Site 0025 | Medford | Oregon | 97504 | United States |
| Amphastar Site 0026 | Portland | Oregon | 97202 | United States |
| Amphastar Site 0029 | North Charleston | South Carolina | 29406 | United States |
| Amphastar Site 0031 | El Paso | Texas | 79903 | United States |
| Amphastar Site 0030 | New Braunfels | Texas | 78130 | United States |
| Amphastar Site 0033 | Richmond | Virginia | 23229 | United States |
| Amphastar Site 0034 | Seattle | Washington | 98105 | United States |
| 3780129 | 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. |
| 10919679 | 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. |
| 11061773 | 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. |
| 10936150 | 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. |
| 9872837 | Background | Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179-87. doi: 10.1164/ajrccm.159.1.9712108. |
| 31959019 | Derived | Kerwin EM, Tashkin DP, Korenblat PE, Greos LS, Pearlman DS, Bensch GW, Miller SD, Marrs T, Luo MZ, Zhang JY. Long-term safety and efficacy studies of epinephrine HFA metered-dose inhaler (Primatene(R) Mist): a two-stage randomized controlled trial. J Asthma. 2021 May;58(5):633-644. doi: 10.1080/02770903.2020.1713147. Epub 2020 Jan 20. |
| ID | Term |
|---|---|
| D001249 | Asthma |
| D004417 | Dyspnea |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D012120 | Respiration Disorders |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D004837 | Epinephrine |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
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