Clinical trial NCT01460511: Evaluation of Efficacy and Safety of E004 in Children With Asthma
Official title: Phase III Study of Epinephrine Inhalation Aerosol for Evaluation of Efficacy and Safety of E004 in Children With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Mild bronchial asthma
Lead sponsor: Amphastar Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2011-10-27
Enrollment: 70
Sex: ALL
Minimum age (years): 4
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, randomized, double-blinded, placebo-controlled, parallel, 4-week study in 60 pediatric patients (4-11 years old) with asthma, comparing E004 with Placebo HFA-MDI in pediatric patients who are 4-11 years of age with asthma.


Eligibility criteria: Inclusion Criteria:

* Generally healthy male, and premenarchal female, children aged 4 - 11 years upon Screening.
* With documented asthma, requiring inhaled epinephrine or beta2-agonist treatment, with or without concurrent anti-inflammatory therapies for at least 6-months prior to Screening.
* Being capable of performing spirometry for FEV1
* Satisfying criteria of asthma
* Can tolerate withholding treatment with inhaled bronchodilators and other allowed medications for the minimum washout periods
* Demonstrating a Screening Baseline FEV1 that is 50 - 90% of Polgar predicted normal value.
* Demonstrating an Airway Reversibility,
* Demonstrating satisfactory techniques in the use of a metered-dose inhaler (MDIs) and a hand held peak expiratory flow meter, after training.
* Has been properly consented to participate in this study.

Exclusion Criteria:

* Any current or past medical conditions that, per investigator discretion, might significantly affect pharmacodynamic responses to the study drugs
* Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, or malignant diseases.
* Known intolerance or hypersensitivity to any component of the study drugs
* Recent infection of the respiratory tract
* Use of prohibited medications
* Having been on other investigational drug/device studies in the last 30 days prior to screening.

Primary outcomes:
measure: Primary Efficacy Endpoint AUC of FEV1's relative change
timeFrame: Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Secondary outcomes:
measure: AUC of FEV1 volume changes (AUC of change in FEV1)
timeFrame: Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
measure: Maximum of change in FEV1% (Fmax)
timeFrame: Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
measure: Curves of change in FEV1, and change in FEV1%, versus time
timeFrame: Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
measure: Time to onset of bronchodilator effect (to onset), determined the time point (within 60 minutes) where FEV1 first reaches ≥12% above Same-Day Baseline.
timeFrame: Study Visits 1and 3 within 60 minutes post dose
measure: The time to peak FEV1 effect (tmax), defined as the time of Fmax.
timeFrame: Study Visits 1 and 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
measure: Duration of efficacy (duration), defined as the total length of time when ΔFEV1% reaches and stays ≥12% above Same-Day Baseline.
timeFrame: Study Weeks 1and 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
measure: Percentage of positive responders (R%), including all subjects whose Fmax reaches ≥12% above Same-Day Baseline.
timeFrame: Study Weeks 1 and 3 within 60 minutes post dose
measure: Mean daily morning pre-dose Peak Expiratory Flow Rate (PEF)
timeFrame: daily pre-dose
measure: Evaluation of Vital Signs
timeFrame: predose, and 3, 20, 60, 360 minutes post-dose
measure: 12-lead ECG
timeFrame: Pre-dose and , 3, 20 and 60 minutes post-dose (Study Visits 1 and 3)
measure: Albuterol HFA usage for rescue relief of acute asthma symptoms
timeFrame: Study Visits 1, 2, and 3, within 30 min predose
Other outcomes:
Locations:
city: Costa Mesa
country: United States
facility: Amphastar Site 5
state: California
city: Orange
country: United States
facility: Amphastar Site 8
state: California
city: Stockton
country: United States
facility: Amphastar Site 4
state: California
city: Medford
country: United States
facility: Amphastar Site 2
state: Oregon
city: Portland
country: United States
facility: Amphastar Site 1
state: Oregon
city: North Charleston
country: United States
facility: Amphastar Site 7
state: South Carolina
city: El Paso
country: United States
facility: Amphastar Site 3
state: Texas
city: San Antonio
country: United States
facility: Amphastar Site 6
state: Texas
Study officials:
affiliation: Amphastar Pharmaceuticals, Inc.
name: John Gao, M.D.
role: STUDY_CHAIR
References:
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. doi: 10.1002/j.1552-4604.1991.tb04969.x.
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. doi: 10.1016/S1081-1206(10)61014-9.
citation: 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.
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.
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. doi: 10.1378/chest.118.2.522.