E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with moderate to very severe chronic obstructive pulmonary disease (COPD) |
Pacientes con enfermedad pulmonar obstructiva crónica (EPOC) de moderada a muy grave |
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E.1.1.1 | Medical condition in easily understood language |
Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by chronic obstruction of lung airflow that interferes with normal breathing and is not fully reversible. |
Enf. pulmonar obstructiva crónica (EPOC) es una enf. pulmonar caracterizada por la obstrucción crónica del flujo de aire al pulmón que interfiere con la respiración normal y no es del todo reversible |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy in reducing exacerbations with Symbicort pMDI 160/4.5 µg x 2 actuations BID versus formoterol Turbuhaler 4.5 µg x 2 inhalations BID in COPD subjects |
Comparar la eficacia en cuanto a reducción de las exacerbaciones con Symbicort pMDI 160/4,5 µg x 2 aplicaciones BID frente a formoterol Turbuhaler 4,5 µg x 2 inhalaciones BID en pacientes con EPOC |
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E.2.2 | Secondary objectives of the trial |
To compare Symbicort pMDI and formoterol Turbuhaler treatments on the time to the first COPD exacerbation To compare Symbicort pMDI and formoterol Turbuhaler treatments on health status/health-related quality of life To compare Symbicort pMDI and formoterol Turbuhaler treatments on pulmonary function To compare Symbicort pMDI and formoterol Turbuhaler treatments on rescue medication use To compare Symbicort pMDI and formoterol Turbuhaler treatments on nocturnal awakenings To demonstrate the safety of Symbicort pMDI compared to that of formoterol Turbuhaler in subjects with COPD |
Comparar los tratamientos con Symbicort pMDI y formoterol Turbuhaler respecto al tiempo hasta la primera exacerbación de la EPOC Comparar los tratamientos con Symbicort pMDI y formoterol Turbuhaler respecto al estado de salud/la calidad de vida relacionada con la salud Comparar los tratamientos con Symbicort pMDI y formoterol Turbuhaler respecto a la función pulmonar Comparar los tratamientos con Symbicort pMDI y formoterol Turbuhaler respecto al uso de medicación de rescate Comparar los tratamientos con Symbicort pMDI y formoterol Turbuhaler respecto a los despertares nocturnos Demostrar la seguridad de Symbicort pMDI en comparación con la de formoterol Turbuhaler en pacientes con EPOC |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed Informed Consent at Visit 1 obtained prior to conducting any study-related procedures including withdrawal of medications. 2. Outpatients; men or women ? 40 years of age. 3. A current clinical diagnosis of COPD with COPD symptoms for more than 1 year, according to the GOLD guidelines. 4. Current or previous smoker with a smoking history equivalent to 10 or more pack years (1 pack year = 20 cigarettes smoked per day for 1 year). 5. Post-bronchodilator FEV1/forced vital capacity (FVC) <0.7 (70%) and FEV1 ? 70% of predicted normal (PN) value. 6. Documented use of a short-acting inhaled bronchodilator (?2-agonists or anticholinergics) as rescue medication within 6 months prior to study start. 7. A score of ? 2 on the modified medical research council (MMRC) dyspnea scale. 8. Documented history of ?1 moderate or severe COPD exacerbation(s) that required treatment with systemic (oral, IM, IV) corticosteroids (a minimum 3 day course of an oral corticosteroid treatment or single depot corticosteroid injection), or hospitalization (defined as an inpatient stay or >24 hour stay in an observation area in the emergency department or other equivalent facility depending on the country and healthcare system) within 2-52 weeks before Visit 1 (i.e., not within the 14 days prior to Visit 1). A history of an exacerbation treated exclusively with antibiotics will not be considered adequate. |
1. Firma del consentimiento informado en la visita 1, obtenido antes de realizar ningún procedimiento relacionado con el ensayo, incluida la retirada de medicamentos. 2. Pacientes ambulatorios; varones o mujeres ? 40 años. 3. Diagnóstico clínico actual de EPOC con síntomas de EPOC durante más de 1 año, de acuerdo con las directrices GOLD. 4. Tabaquismo actual o previo con antecedentes de tabaquismo equivalentes a 10 paquetes-año o más (1 paquete-año = 20 cigarrillos fumados al día durante 1 año). 5. FEV1/capacidad vital forzada (FVC) post-broncodilatador <0,7 (70%) y FEV1 ? 70% del valor normal predictivo (NP) post-broncodilatador. 6. Uso documentado de un broncodilatador inhalado de acción corta (?2-agonistas o anticolinérgicos) como medicación de rescate dentro de los 6 meses previos al comienzo del ensayo. 7. Una puntuación ? 2 en la escala de disnea Medical Research Council modificada (MRCm). 8. Antecedentes documentados de ?1 exacerbación moderada o grave de EPOC que precisó tratamiento con corticosteroides sistémicos (oral, IM, IV) (un ciclo mínimo de 3 días de un tratamiento con corticosteroides orales o una única inyección de corticosteroides depot) u hospitalización (definida como una estancia hospitalaria o una estancia >24 horas en un área de observación en un servicio de urgencias o una instalación equivalente dependiendo del país y del sistema sanitario) en el plazo entre 2 y 52 semanas antes de la visita 1 (esto es, no dentro de los 14 días previos a la visita 1). Los antecedentes de una exacerbación tratada exclusivamente con antibióticos no se considerarán suficientes. |
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E.4 | Principal exclusion criteria |
1. A history of asthma at or after 18 years of age. 2. Subjects with significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure (including significant cor pulmonale), uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator. 3. Known homozygous alpha-1 antitrypsin deficiency. 4. Any significant disease or disorder (e.g., gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results of the study, or the subject?s ability to participate in the study. 5. A history of malignancy (except basal cell carcinoma) within the past 5 years. 6. Active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease, or other active pulmonary diseases. 7. Subjects who have needed additions or alterations to their usual maintenance or change in formulation of rescue therapy for COPD due to worsening symptoms within the 14 days prior to Visit 1 and up to Visit 3. 8. CXR (frontal and lateral) with suspicion of pneumonia or other condition/abnormality that will require additional investigation/treatment, or put the subject at risk because of participation in the study. 9. Risk factors for pneumonia: immune suppression (HIV, lupus) or other risk for pneumonia (e.g. neurological disorders affecting control of the upper airway, such as Parkinson?s disease, myasthenia gravis, etc.). 10. Pneumonia not resolved within 14 days of Visit 1. 11. Moderate or severe COPD exacerbation that has not resolved within 14 days prior to Visit 1 or a moderate or severe COPD exacerbation that occurs between Visit 1 and Visit 2. 12. Long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. |
1. Antecedentes de asma a los 18 años de edad o después. 2. Pacientes con cardiopatía isquémica significativa o inestable, arritmia, miocardiopatía, insuficiencia cardíaca (incluido cor pulmonale significativo), hipertensión no controlada definida por el investigador o cualquier otro trastorno cardiovascular relevante a criterio del investigador. 3. Déficit homocigótico conocido de alfa-1 antitripsina. 4. Cualquier enfermedad o trastorno significativo (p. ej., gastrointestinal, hepático, renal, neurológico, musculoesquelético, endocrino, metabólico, maligno, psiquiátrico, deterioro físico importante) que, en opinión del investigador, podría poner al paciente en riesgo debido a la participación en el ensayo o influir en los resultados del ensayo o la capacidad del paciente para participar en el ensayo. 5. Antecedentes de tumor maligno (excepto carcinoma basocelular) dentro de los últimos 5 años. 6. Tuberculosis activa, cáncer de pulmón, bronquiectasias, sarcoidosis, fibrosis pulmonar, hipertensión pulmonar primaria, enfermedad pulmonar intersticial u otra enfermedad pulmonar activa. 7. Pacientes que hayan necesitado adiciones o modificaciones a su tratamiento habitual de mantenimiento o cambio en la formulación del tratamiento de rescate para la EPOC, debido a empeoramiento de los síntomas dentro de los 14 días previos a la visita 1 y hasta la visita 3. 8. RxT (frontal y lateral) con sospecha de neumonía u otro problema/anomalía que precisará investigación/tratamiento adicional, o pondrá al paciente en riesgo debido a la participación en el ensayo. 9. Factores de riesgo de neumonía: inmunosupresión (VIH, lupus) u otro riesgo de neumonía (p. ej., trastornos neurológicos que afectan al control de las vías aéreas superiores, como enfermedad de Parkinson, miastenia grave, etc.). 10. Neumonía no resuelta en el plazo de 14 días antes de la visita 1. 11. Exacerbación moderada o grave de la EPOC que no se ha resuelto en el plazo de 14 días antes de la visita 1 o exacerbación moderada o grave de la EPOC que se produce entre la visita 1 y la visita 2. 12. Oxigenoterapia a largo plazo (OTLP) u oxigenoterapia nocturna, necesarias durante más de 12 horas al día. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The rate of moderate and severe COPD exacerbations defined as: Worsening of ?2 major symptoms or worsening of 1 major symptom together with ?1 minor symptom for ?2 consecutive days. Moderate exacerbation: treatment of symptoms with systemic corticosteroids (?3 days) and/or antibiotics. Severe exacerbation: symptoms that require hospitalization (including >24 hours in ED/urgent care setting). Major symptoms: - Dyspnea - Increase in sputum volume - Increase in sputum color/purulence Minor symptoms: - Sore throat - Colds (nasal discharge and/or nasal congestion) - Fever without other cause - Increased cough - Increased wheeze |
Tasa de exacerbación moderada y grave de EPOC definida como: Empeoramiento de ? 2 síntomas mayores o empeoramiento de 1 síntoma mayor junto con ? 1 síntoma menor durante ? 2 días consecutivos. Exacerbación moderada: tratamiento de síntomas con corticosteroides sistémicos (?3 días) y/o antibióticos. Exacerbación grave: síntomas que precisan hospitalización (incluidas >24 horas en un servicio de urgencias). Síntomas mayores: - Disnea - Aumento del volumen de esputo - Aumento del color/la purulencia del esputo Síntomas menores: - Dolor de garganta - Resfriados (secreción nasal y/o congestión nasal) - Fiebre sin otra causa - Aumento de la tos - Aumento de las sibilancias |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study Visit: Enrolment W -5 Run-in W -4 Randomization W 0 Treatment W 4, 8, 17 EoT W 26 |
Visitas del estudio: Reclutamiento: Semana -5 Preinclusión: Semana -4 Aleatorización: Semana 0 Tratamiento: Semana 4, 8, 17 FdT: Semana 26 |
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E.5.2 | Secondary end point(s) |
- Time to first moderate or severe COPD exacerbation - St. George´s Respiratory Questionnaire (SGRQ) - Pre-dose/pre-bronchodilator FEV1 at the study site - Total rescue medication use (average puffs/day) - Nights with awakening due to COPD |
- Tiempo hasta la primera exacerbación moderada o grave de la EPOC - Cuestionario respiratorio de St. George (SGRQ) - Volumen espiratorio forzado en un segundo (FEV1) pre-dosis/pre-broncodilatador en el centro del ensayo - Utilización total de medicamentos de rescate (media de inhalaciones/día) - Noches con despertares debidos a EPOC |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Study Visit: Enrolment W -5 Run-in W -4 Randomization W 0 Treatment W 4, 8, 17 EoT W 26 |
Visitas del estudio: Reclutamiento: Semana -5 Preinclusión: Semana -4 Aleatorización: Semana 0 Tratamiento: Semana 4, 8, 17 FdT: Semana 26 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Bulgaria |
Chile |
Czech Republic |
European Union |
Mexico |
Poland |
South Africa |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS |
Última visita del último paciente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 8 |