- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT01737905
Evaluation of Efficacy and Safety for Single Dose of E004 in Children With Asthma
Evaluation of Efficacy and Safety for Single Dose of E004 in Children With Asthma (A Randomized, Double-Blind, Placebo-Controlled, Crossover, Single Dose Study in 4 - 11 Year Old Children With Asthma)
This is a multi-center, randomized, double-blinded, placebo-controlled, crossover, single dose study in 24 pediatric patients (4-11 years old) with asthma.
The entire study consists of (i) a Screening Visit and (ii) a Study Period with two (2) Study Visits. All study subjects must be properly consented, under adult supervision, and screened against the inclusion and exclusion criteria, at the Screening Visit.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
This is a randomized, double-blinded, placebo-controlled, crossover, single dose study to be conducted in pediatric patients (4 - 11 years) with asthma.
The main features of the study design are:
The entire study consists of a Screening Visit, and a Study Period consisting of two (2) crossover Study Visits separated by a 2 to 14-day interval. All study subjects must be properly consented, under adult supervision, and screened against the inclusion and exclusion criteria at the Screening Visit and confirmed for enrollment on Visit 1. Efficacy and safety evaluations of E004 are conducted at each Study Visit.
This study employs two (2) double-blinded treatment arms as outlined in Table 2. A double-blinded design will be applied to E004 (Arm T) and Placebo-HFA (Arm P) since they are identical in all physical attributes and share a comparable formulation.
The enrolled subjects will be randomized into two sequences (as follows) to participate in two (2) crossover Study Visits with a 2 - 14 day interval between visits. Randomization is achieved using a ratio of 1:1.
Use E004 (T) and Placebo (P) in Visits 1 and 2, respectively or use Placebo (P) and E004 (T) in Visits 1 and 2, respectively
Subjects will be trained at the screening visit and each Study Visit for the correct dosing and spirometry methods. Under the supervision of dosing monitor, subjects will self-administer two (2) inhalations of the randomized study treatment, with a ~1 min interval at each Study Visit.
For the Screening and Study Visits, the subjects will be required to be at the site for a 30 minute "resting period". This resting period is designed to maintain a stable and consistent physical status of the subjects prior to the start of the baseline FEV1 procedures. For the Screening Visit, this period will begin upon subject arrival. For the Study Visits, the period will begin at the end of the option breakfast (or upon arrival if the breakfast is declined).
For each Study Visit, subjects will need to arrive at the study site early enough to complete all necessary baseline evaluations. The study site will provide an optional breakfast but it must be eaten at least 30 minutes prior to the pre-dose baseline FEV1 measurements. The optional breakfast will be light, and contain no added sugar. If the subjects decline the breakfast (i.e. they have already eaten a light breakfast prior to arriving), they are required to remain at the site for at least 30 minutes prior to the start of the Baseline FEV1 measurements, in order to maintain a stable physical status.
Baseline vital signs and safety evaluations will be taken prior to the pre-dose baseline FEV1 measurement. These can be performed during the 30 minute "resting period". Efficacy of the treatments at each visit will be evaluated based on spirometric measurements of serial FEV1 determined at the Pre-dose Baseline, and the seven (7) serial Post-dose FEV1 responses at 5, 30, 60, 120, 150, 180) and 240 minutes.
This study will be conducted with a double-blinded technique. This means neither the subject nor the site staff will be aware of the identity of the treatment arm since both study treatments are in identical looking containers.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 3
Contatti e Sedi
Luoghi di studio
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California
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Cypress, California, Stati Uniti, 90630
- West Coast Clinical Trials Global
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Oregon
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Medford, Oregon, Stati Uniti, 97504
- The Clinical Research Institute of Southern Oregn, PC
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Portland, Oregon, Stati Uniti, 97202
- Transitional Clinical Research, Inc. Allergy Associates Research Center
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Texas
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El Paso, Texas, Stati Uniti, 79903
- Western Sky Medical
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San Antonio, Texas, Stati Uniti, 78229
- Sylvana Research Assocaites
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Washington
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Seattle, Washington, Stati Uniti, 98115
- ASTHMA, Inc. Clinical Research Center
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Generally healthy male, and premenarchal female, children ages 4 - 11 years upon Screening.
- With documented asthma, requiring inhaled epinephrine or β2-agonist treatment, with or without concurrent anti-inflammatory therapies including orally inhaled corticosteroids, for at least 6-months prior to Screening.
- Being capable of performing spirometry for FEV1 measurements.
- Satisfying criteria of asthma stability, defined as no significant changes in asthma therapy (with the exception of switching LABA to SABA, adjustment of ICor SABA, etc, per investigator discretion) and no asthma-related hospitalization or emergency room visits, within 4 weeks prior to Screening.
- Can tolerate withholding treatment with inhaled bronchodilators and other allowed medications for the minimum washout periods indicated in Appendix II prior to the Screening Baseline FEV1 testing.
- Demonstrating a Mean Screening Baseline FEV1 (MSBF) that is 50.0% - 90% of Polgar predicted normal value.
- Demonstrating an Airway Reversibility, i.e., FEV1 values ≥12% increase based upon volume compared with MSBF, within 30 min after 2 inhalations (440 mcg, epinephrine base) of previously marketed Epinephrine CFC-MDI, labeled "For Investigational Use Only". There will be up to 5 reversibility time points, each with up to 5 maneuvers that can be conducted anytime within 30 min post-dose.
- Demonstrating satisfactory techniques in the use of a metered-dose inhaler (MDI).
- 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, such as significant systemic or respiratory diseases (e.g., cystic fibrosis, bronchiectasis, active tuberculosis, emphysema, nonreversible pulmonary diseases), other than asthma.
- Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, or malignant diseases.
- Known intolerance or hypersensitivity to any component of the study drugs (i.e., Epinephrine, HFA-134a, CFC-12, CFC-114, polysorbate-80, thymol, ethanol, ascorbic acid, nitric acid, and hydrochloric acid), as well as the rescue Albuterol HFA inhalers (i.e., Albuterol, HFA-134a, ethanol, and oleic acid).
- Recent infection of the upper respiratory tract (within 2 weeks), or lower respiratory tract (within 4 weeks), before screening.
- Use of prohibited medications per Appendix II.
- Having been on other investigational drug/device studies in the last 30 days prior to screening.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione incrociata
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: Arm T
Experimental arm utilizing Epinephrine HFA-MDI (E004)
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Single dose 125 mcg/inhalation, 2 inhalations
|
|
Comparatore placebo: Arm P
Placebo comparator arm utilizing Placebo-HFA
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Single dose 0 mcg/inhalation, 2 inhalations
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Bronchodilator effect
Lasso di tempo: up to 30 min pre-dose, postdose up to 3 hours
|
Bronchodilator effect expressed as AUC of FEV1's relative change from the same day baseline (pre-dose) versus time up to 3 hours, defined as AUC(0-3) of change in FEV1%.
The difference of primary endpoints of E004 and Placebo will be evaluated statistically.
|
up to 30 min pre-dose, postdose up to 3 hours
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
AUC analysis
Lasso di tempo: up to 30 min pre-dose, postdose up to 3 hours
|
The comparative analysis of AUC of FEV1 versus time
|
up to 30 min pre-dose, postdose up to 3 hours
|
|
Evaluation of FEV1 volume changes
Lasso di tempo: up to 30 min pre-dose, postdose up to 3 hours
|
Evaluation of AUC(0-3) and AUC(0-4) of FEV1 volume changes (AUC of ΔFEV1)
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up to 30 min pre-dose, postdose up to 3 hours
|
|
Change in FEV1
Lasso di tempo: up to 30 min pre-dose, postdose up to 3 hours
|
Evaluation of Maximum of change in FEV1% (Fmax)
|
up to 30 min pre-dose, postdose up to 3 hours
|
|
Time response
Lasso di tempo: up to 30 min pre-dose, postdose up to 3 hours
|
Evaluation of time response curves of change in FEV1 and FEV1%
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up to 30 min pre-dose, postdose up to 3 hours
|
|
Time to onset of bronchodilator effect
Lasso di tempo: up to 30 min pre-dose, postdose up to 3 hours
|
Determination of time to onset of bronchodilator effect (Tonset), determined by the time point (within 60 minutes) where FEV1 first reaches greater than or equal to 12% above Same-Day Pre-dose Baseline
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up to 30 min pre-dose, postdose up to 3 hours
|
|
Time to peak FEV1 effect
Lasso di tempo: up to 30 min pre-dose, postdose up to 3 hours
|
The time to peak FEV1 effect (Tmax), defined as the time of Fmax
|
up to 30 min pre-dose, postdose up to 3 hours
|
|
Duration of efficacy
Lasso di tempo: up to 30 min pre-dose, postdose up to 3 hours
|
Evaluation of duration of efficacy (Tduration), defined as the total length of time when the change in FEV1% reaches and stays greater than or equal to 12% above Same-Day Pre-dose Baseline
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up to 30 min pre-dose, postdose up to 3 hours
|
|
Percentage of positive responders
Lasso di tempo: up to 30 min pre-dose, postdose up to 3 hours
|
Evaluation of percentage of positive responders (R%), including all subjects whose Fmax reaches more than or equal to 12% above Same-Day Pre-dose Baseline
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up to 30 min pre-dose, postdose up to 3 hours
|
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Vital Signs
Lasso di tempo: Screening Visit: baseline up to 30 min predose and 30 min post dose; Visits 1-2: Baseline upt o 30 min predose and 3, 20, 60, and 240 min post-dose
|
Vital signs (SBP/DBP, and heart rate) will be monitored at the Screening Visit and at Study Visits 1 and 2
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Screening Visit: baseline up to 30 min predose and 30 min post dose; Visits 1-2: Baseline upt o 30 min predose and 3, 20, 60, and 240 min post-dose
|
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12-lead ECG (Routine and QT/QTc)
Lasso di tempo: Screening Visit: baseline up to 30 min predose and 30 min post dose; Visits 1-2: Baseline upt o 30 min predose and 3, 20, and 60 min post-dose
|
A 12-lead ECG (Routine and QT/QTc) will be recorded at Screening Visit and at the Study Visits 1 and 2
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Screening Visit: baseline up to 30 min predose and 30 min post dose; Visits 1-2: Baseline upt o 30 min predose and 3, 20, and 60 min post-dose
|
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Lab Tests
Lasso di tempo: prior to first dose
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Lab tests for CBC, blood chemistry panel (8-hr fasted), and urinalysis will be performed at screening
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prior to first dose
|
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Albuterol HFA Usage
Lasso di tempo: up to 30 min predose
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Albuterol HFA usage for rescue relief of acute asthma symptoms will be recorded at each visit
|
up to 30 min predose
|
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Concomitant Medications
Lasso di tempo: up to 30 min predose
|
Concomitant medications will be reviewed and recorded
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up to 30 min predose
|
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Adverse Events
Lasso di tempo: predose and up to 3 hours postdose
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All Adverse Events/side effects will be recorded and assessed
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predose and up to 3 hours postdose
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Collaboratori e investigatori
Sponsor
Investigatori
- Direttore dello studio: Selina Su, MPH, Amphastar Pharmaceuticals, Inc.
Pubblicazioni e link utili
Pubblicazioni generali
- 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.
- 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.
- 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.
- 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. doi: 10.1378/chest.118.2.522.
- 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.
- 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.
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie delle vie respiratorie
- Malattie del sistema immunitario
- Malattie polmonari
- Ipersensibilità, immediata
- Malattie bronchiali
- Malattie polmonari, ostruttive
- Ipersensibilità respiratoria
- Ipersensibilità
- Asma
- Effetti fisiologici delle droghe
- Agenti adrenergici
- Agenti neurotrasmettitori
- Meccanismi molecolari dell'azione farmacologica
- Agenti autonomi
- Agenti del sistema nervoso periferico
- Alfa-agonisti adrenergici
- Agonisti adrenergici
- Agenti broncodilatatori
- Agenti antiasmatici
- Agenti del sistema respiratorio
- Beta-agonisti adrenergici
- Simpaticomimetici
- Agenti vasocostrittori
- Midriatici
- Epinefrina
Altri numeri di identificazione dello studio
- API-E004-CL-D2
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .