A Phase IIIb Study to Evaluate the Efficacy of Umeclidinium/Vilanterol (UMEC/VI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
9 de octubre de 2017 actualizado por: GlaxoSmithKline
A 12 Week, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy of Umeclidinium/Vilanterol 62.5/25mcg in Subjects With COPD
This study is a 12-week, multicenter, randomized, double blind, parallel group, placebo-controlled study.
The purpose of this study is to replicate the therapeutic benefit of UMEC/VI 62.5/25 microgram (mcg) on health-related quality of life as reflected by St. George's Respiratory Questionnaire (SGRQ) scores and symptoms as reflected by rescue medication use observed in the 6 month placebo controlled study (DB2113373). Lung function will be assessed as it provides an objective measure to support the subjective patient reported outcomes of SGRQ and rescue medication use. The study is intended to provide additional evidence to support the use of UMEC/VI for the maintenance treatment of COPD Approximately 496 subjects will be randomized from approximately 62 centers in order to ensure 422 subjects complete 12 weeks of treatment. Eligible subjects will be randomized to UMEC/VI 62.5/25mcg or placebo in a 1:1 ratio. All treatments will be administered once-daily in the morning via a Dry Powder Inhaler (DPI).
There will be a total of 5 clinic visits. The total duration of study participation will be approximately 15 weeks. All subjects will be provided with albuterol/salbutamol to use as needed for the relief of COPD symptoms throughout the run-in and double-blind treatment periods.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
498
Fase
- Fase 3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Berlin, Alemania, 10717
- GSK Investigational Site
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Berlin, Alemania, 10119
- GSK Investigational Site
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Berlin, Alemania, 10629
- GSK Investigational Site
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Hamburg, Alemania, 22143
- GSK Investigational Site
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Hessen
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Kassel, Hessen, Alemania, 34121
- GSK Investigational Site
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Niedersachsen
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Weyhe-Leeste, Niedersachsen, Alemania, 28844
- GSK Investigational Site
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Schleswig-Holstein
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Reinfeld, Schleswig-Holstein, Alemania, 23858
- GSK Investigational Site
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Dupnitza, Bulgaria, 2600
- GSK Investigational Site
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Gabrovo, Bulgaria, 5300
- GSK Investigational Site
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Kyustendil, Bulgaria, 2500
- GSK Investigational Site
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Montana, Bulgaria
- GSK Investigational Site
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Sevlievo, Bulgaria, 5400
- GSK Investigational Site
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Sliven, Bulgaria, 8800
- GSK Investigational Site
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Sofia, Bulgaria, 1336
- GSK Investigational Site
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Arizona
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Phoenix, Arizona, Estados Unidos, 85006
- GSK Investigational Site
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California
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Upland, California, Estados Unidos, 91786
- GSK Investigational Site
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Florida
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Clearwater, Florida, Estados Unidos, 33765-2616
- GSK Investigational Site
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Missouri
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Saint Charles, Missouri, Estados Unidos, 63301
- GSK Investigational Site
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South Carolina
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Anderson, South Carolina, Estados Unidos, 29621
- GSK Investigational Site
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Easley, South Carolina, Estados Unidos, 29640
- GSK Investigational Site
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Mount Pleasant, South Carolina, Estados Unidos, 29464
- GSK Investigational Site
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Rock Hill, South Carolina, Estados Unidos, 29732
- GSK Investigational Site
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Seneca, South Carolina, Estados Unidos, 29678
- GSK Investigational Site
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Union, South Carolina, Estados Unidos, 29379
- GSK Investigational Site
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Texas
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San Antonio, Texas, Estados Unidos, 78229
- GSK Investigational Site
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Ekaterinburg, Federación Rusa, 620039
- GSK Investigational Site
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Moscow, Federación Rusa, 117997
- GSK Investigational Site
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Novosibirsk, Federación Rusa, 630099
- GSK Investigational Site
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Saint Petesburg, Federación Rusa, 195030
- GSK Investigational Site
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Sestroretsk, Federación Rusa, 197706
- GSK Investigational Site
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St. Petersburg, Federación Rusa, 194356
- GSK Investigational Site
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St. Petersburg, Federación Rusa, 198216
- GSK Investigational Site
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Stavropol, Federación Rusa, 355017
- GSK Investigational Site
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Ulyanovsk, Federación Rusa, 432063
- GSK Investigational Site
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Voronezh, Federación Rusa, 394018
- GSK Investigational Site
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Balassagyarmat, Hungría, 2660
- GSK Investigational Site
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Budapest, Hungría, 1085
- GSK Investigational Site
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Budaörs, Hungría, 2040
- GSK Investigational Site
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Debrecen, Hungría, 4032
- GSK Investigational Site
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Gödöllő, Hungría, 2100
- GSK Investigational Site
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Nyíregyháza, Hungría, 4400
- GSK Investigational Site
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Szeged, Hungría, 6722
- GSK Investigational Site
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Szikszó, Hungría, 3800
- GSK Investigational Site
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Cluj-Napoca, Rumania, 400371
- GSK Investigational Site
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Codlea, Rumania, 505100
- GSK Investigational Site
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Craiova, Rumania, 200642
- GSK Investigational Site
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Deva, Rumania, 330084
- GSK Investigational Site
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Iasi, Rumania, 700115
- GSK Investigational Site
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Pitesti, Rumania, 110084
- GSK Investigational Site
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Kharkiv, Ucrania, 61124
- GSK Investigational Site
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Kharkiv, Ucrania, 61002
- GSK Investigational Site
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Kiev, Ucrania, 03680
- GSK Investigational Site
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Kyiv, Ucrania, 02232
- GSK Investigational Site
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Kyiv, Ucrania, 01114
- GSK Investigational Site
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
40 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Type of subject: Outpatient.
- Informed Consent: A signed and dated written informed consent prior to study participation.
- Age: 40 years of age or older at Visit 1.
- Gender: Male and female subjects are eligible to participate in the study.
- A female subject is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile (For example [e.g.] age appropriate, >45 years, in the absence of hormone replacement therapy; or child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label, if appropriate, and the instructions of the physician for the duration of the study screening to follow-up contact): abstinence; oral contraceptive (either combined or progestogen alone); injectable progestogen; implants of levonorgestrel; estrogenic vaginal ring; percutaneous contraceptive patches; intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label; male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study (this male is the sole partner for that subject); and double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository).
- Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society.
- Smoking History: Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years [number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g. 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years)]. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar use cannot be used to calculate pack-year history.
- Severity of Disease: A pre and post-albuterol/salbutamol FEV1/ Forced Vital Capacity (FVC) ratio of <0.70 and a post-albuterol/salbutamol FEV1 of <=70% of predicted normal values calculated using National Health and Nutrition Examination Survey (NHANES) III reference equations at Visit 1.
- Dyspnea: A score of >=2 on the Modified Medical Research Council (mMRC) Dyspnea Scale at Visit 1.
Exclusion Criteria:
- Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
- Asthma: A current diagnosis of asthma.
- Other Respiratory Disorders: Known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions. A subject who, in the opinion of the investigator, has any other significant respiratory conditions in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease.
- Other Diseases/Abnormalities: Any subject who is considered unlikely to survive the duration of the study period or has any rapidly progressing disease or immediate life-threatening illness (e.g. cancer). In addition, any subject who has any condition (e.g. neurological condition) that is likely to affect respiratory function should not be included in the study.
- Severe Hepatic Impairment: Patients with severe hepatic impairment (Child-Pugh class C) should be excluded unless, in the opinion of the investigator, the benefit is likely to outweigh the risk.
- Unstable or life threatening cardiac disease: UMEC/VI should be used with caution in subjects with severe cardiovascular disease. In the opinion of the investigator, use should only be considered if the benefit is likely to outweigh the risk in conditions such as: myocardial infarction or unstable angina in the last 6 months; unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months; New York Heart Association (NYHA) Class IV heart failure.
- Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, sympathomimetic, lactose/milk protein or magnesium stearate.
- Antimuscarinic effects: Subjects with medical conditions such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction should only be included if, in the opinion of the study physician, the benefit outweighs the risk.
- Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
- Lung Resection: Lung volume reduction surgery within the 12 months prior to Visit 1.
- 12-Lead Electrocardiogram (ECG): Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. The Investigator will determine the clinical significance of each abnormal ECG finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial. Subjects with the following abnormalities are excluded from participation in the study: Atrial fibrillation with rapid ventricular rate >120 beats per minute (bpm); Sustained or non-sustained ventricular tachycardia; Second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator had been inserted).
- Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
- Interactions: Concomitant administration with beta-blockers and strong Cytochrome P450 3A4 (CYP3A4) inhibitors is only permitted if, in the Investigator's opinion, the likely benefit outweighs the potential risk.
- Medications Prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1: Depot corticosteroids (12 weeks), systemic, oral or parenteral corticosteroids (6 weeks), antibiotics (for lower respiratory tract infection) (6 weeks), Long acting Beta-Agonist (LABA)/ Inhaled Corticosteroid (ICS) combination products if LABA/ICS therapy is discontinued completely (30 days), LABA/ICS combination products only if discontinuing LABA/ICS therapy and switching to ICS monotherapy (48 hours for salmeterol or formoterol component and 14 days for vilanterol component), ICS (dose >1000 mcg/day of fluticasone propionate or equivalent) (30 days), Initiation or discontinuation of ICS use (30 days), Phosphodiesterase 4 (PDE4) Inhibitor (roflumilast) (14 days), Inhaled long acting beta2 agonists (48 hours for salmeterol, formoterol, 14 days for olodaterol, indacaterol), Long-acting muscarinic antagonists (tiotropium, aclidinium, glycopyrronium, umeclidinium) (7 days), LAMA/LABA combination products if LAMA/LABA therapy is discontinued completely (Apply whichever mono component has the longest washout), Theophyllines (48 hours), Oral beta2-agonists (Long-acting [48 hours], short-acting [12 hours]), Inhaled short acting beta2-agonists (4 hours), Inhaled short-acting anticholinergics (4 hours), Inhaled short-acting anticholinergic/short-acting beta2-agonist combination products (4 hours), Any other investigational medication (30 days or within 5 drug half-lives [whichever is longer])
- Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., <=12 hours per day) is not exclusionary.
- Nebulised Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulised therapy.
- Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
- Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
- Affiliation with Investigator Site: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.
- Inability to read: In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete a questionnaire.
- Previous participation in DB2113373 study: Subjects who have previously been assigned a subject number (enrolled) in GlaxoSmithKline study DB2113373.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Umeclidinium/Vilanterol 62.5/25 mcg once daily
The subjects will receive UMEC/VI 62.5/25 mcg, administered as one inhalation once-daily in the morning via a dry powder inhaler (DPI)
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Dry white powder delivered via DPI (2 strips with 30 blisters each, first containing UMEC 62.5 mcg per blister and second containing VI 25 mcg per blister), administered as one inhalation of UMEC/VI 62.5/25 mcg
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Comparador de placebos: Placebo once daily
The subjects will receive placebo, administered as one inhalation once-daily in the morning via a DPI
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Dry white powder delivered via DPI (2 strips with 30 blisters each, both containing lactose with magnesium stearate), administered as one inhalation of placebo
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change From Baseline in Mean St.George's Respiratory Questionnaire (SGRQ) Total Score at Day 84
Periodo de tiempo: Baseline and Day 84
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The SGRQ is a disease-specific questionnaire, self-completed by participants(par), used to evaluate the effect of UMEC/VI on health-related quality of life as compared to placebo in par with COPD.
The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status).
The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts).
Analysis was performed using mixed model repeated measures with covariates of Baseline (scores recorded prior to dosing on Day 1) SGRQ total score, centre group, smoking status, Day, treatment(trt), Day by Baseline interaction and Day by trt interaction, where Day is nominal.
Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline.
Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life.
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Baseline and Day 84
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 84
Periodo de tiempo: Baseline and Day 84
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FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second.
Trough FEV1 measurements were taken electronically by spirometry on Days 28, 56 and 84.
Baseline is defined as the assessment taken pre-dose on Treatment Day 1. Trough FEV1 is defined as the FEV1 value obtained 24 hours after the previous morning's dosing.
Change from Baseline at a particular visit was calculated as the trough FEV1 at that visit minus Baseline.
Analysis was performed using a repeated measures model with covariates of treatment, Baseline , smoking status, center group, day, and day by Baseline and day by treatment interactions.
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Baseline and Day 84
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Change From Baseline (BL) in Mean Number of Puffs of Rescue Medication Per Day Used Over Weeks 1-12
Periodo de tiempo: Week 1 amd Week 12
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Albuterol/salbutamol(A/S) was used as rescue medication and was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout treatment periods.
The number of puffs of rescue medication (A/S) per day over the entire 12 week treatment period was recorded and analyzed.
For rescue use, 'day' is referred as the period between one record of rescue use and the next.
Total puffs of rescue for each day = number of salbutamol puffs + (2 x number of salbutamol nebules).
Analysis performed using mixed model repeated measures with covariates of BL(mean number of total puffs over the duration from First Day; defined as Latest of [7 days before Visit 2 and day after Visit 1] to Last Day(defined as Day before Visit 2)), smoking status, centre group, four-week period, treatment and period by BL interaction.
Change from BL used weeks 1-4, 5-8, and 9-12 as covariates in the model and the overall least squares mean change for weeks 1-12 is estimated.
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Week 1 amd Week 12
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de septiembre de 2014
Finalización primaria (Actual)
1 de marzo de 2015
Finalización del estudio (Actual)
5 de marzo de 2015
Fechas de registro del estudio
Enviado por primera vez
29 de mayo de 2014
Primero enviado que cumplió con los criterios de control de calidad
29 de mayo de 2014
Publicado por primera vez (Estimar)
2 de junio de 2014
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
9 de noviembre de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
9 de octubre de 2017
Última verificación
1 de octubre de 2017
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 201211
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Sí
Descripción del plan IPD
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Datos del estudio/Documentos
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Especificación del conjunto de datos
Identificador de información: 201211Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Formulario de informe de caso anotado
Identificador de información: 201211Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Conjunto de datos de participantes individuales
Identificador de información: 201211Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Informe de estudio clínico
Identificador de información: 201211Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Plan de Análisis Estadístico
Identificador de información: 201211Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Formulario de consentimiento informado
Identificador de información: 201211Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
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Protocolo de estudio
Identificador de información: 201211Comentarios de información: For additional information about this study please refer to the GSK Clinical Study Register
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .