- ICH GCP
- Реестр клинических исследований США
- Клиническое испытание 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.
Обзор исследования
Статус
Условия
Вмешательство/лечение
Подробное описание
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.
Тип исследования
Регистрация (Действительный)
Фаза
- Фаза 3
Контакты и местонахождение
Места учебы
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California
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Cypress, California, Соединенные Штаты, 90630
- West Coast Clinical Trials Global
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Oregon
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Medford, Oregon, Соединенные Штаты, 97504
- The Clinical Research Institute of Southern Oregn, PC
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Portland, Oregon, Соединенные Штаты, 97202
- Transitional Clinical Research, Inc. Allergy Associates Research Center
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Texas
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El Paso, Texas, Соединенные Штаты, 79903
- Western Sky Medical
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San Antonio, Texas, Соединенные Штаты, 78229
- Sylvana Research Assocaites
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Washington
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Seattle, Washington, Соединенные Штаты, 98115
- ASTHMA, Inc. Clinical Research Center
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
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.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Назначение кроссовера
- Маскировка: Четырехместный
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: Arm T
Experimental arm utilizing Epinephrine HFA-MDI (E004)
|
Single dose 125 mcg/inhalation, 2 inhalations
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Плацебо Компаратор: Arm P
Placebo comparator arm utilizing Placebo-HFA
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Single dose 0 mcg/inhalation, 2 inhalations
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Bronchodilator effect
Временное ограничение: 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
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
AUC analysis
Временное ограничение: up to 30 min pre-dose, postdose up to 3 hours
|
The comparative analysis of AUC of FEV1 versus time
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up to 30 min pre-dose, postdose up to 3 hours
|
|
Evaluation of FEV1 volume changes
Временное ограничение: 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)
|
up to 30 min pre-dose, postdose up to 3 hours
|
|
Change in FEV1
Временное ограничение: up to 30 min pre-dose, postdose up to 3 hours
|
Evaluation of Maximum of change in FEV1% (Fmax)
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up to 30 min pre-dose, postdose up to 3 hours
|
|
Time response
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: up to 30 min pre-dose, postdose up to 3 hours
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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
|
|
Vital Signs
Временное ограничение: 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
|
|
12-lead ECG (Routine and QT/QTc)
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
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up to 30 min predose
|
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Concomitant Medications
Временное ограничение: up to 30 min predose
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Concomitant medications will be reviewed and recorded
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up to 30 min predose
|
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Adverse Events
Временное ограничение: predose and up to 3 hours postdose
|
All Adverse Events/side effects will be recorded and assessed
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predose and up to 3 hours postdose
|
Соавторы и исследователи
Спонсор
Следователи
- Директор по исследованиям: Selina Su, MPH, Amphastar Pharmaceuticals, Inc.
Публикации и полезные ссылки
Общие публикации
- 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.
Даты записи исследования
Изучение основных дат
Начало исследования
Первичное завершение (Действительный)
Завершение исследования (Действительный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Оценивать)
Обновления учебных записей
Последнее опубликованное обновление (Оценивать)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Заболевания дыхательных путей
- Заболевания иммунной системы
- Легочные заболевания
- Гиперчувствительность, немедленная
- Бронхиальные заболевания
- Заболевания легких, обструктивные
- Респираторная гиперчувствительность
- Гиперчувствительность
- Астма
- Физиологические эффекты лекарств
- Адренергические агенты
- Нейротрансмиттерные агенты
- Молекулярные механизмы фармакологического действия
- Автономные агенты
- Агенты периферической нервной системы
- Адренергические альфа-агонисты
- Адренергические агонисты
- Бронхорасширяющие агенты
- Антиастматические агенты
- Агенты дыхательной системы
- Адренергические бета-агонисты
- Симпатомиметики
- Сосудосуживающие агенты
- Мидриатики
- Эпинефрин
Другие идентификационные номера исследования
- API-E004-CL-D2
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