Resumen

La EPOC se caracteriza por una limitación del flujo aéreo que no es totalmente reversible, habitualmente progresiva y acompañada de tos crónica, producción de esputo y disnea, lo cual puede constituir una causa importante de discapacidad y ansiedad asociadas a la enfermedad. Además, la EPOC se asocia con una deficiente calidad de vida relacionada con la salud (CVRS). El tratamiento farmacológico se utiliza para mejorar la función pulmonar, reducir los síntomas, disminuir la frecuencia y gravedad de las exacerbaciones, y también para mejorar el estado de salud y la tolerancia al ejercicio. Este es un estudio multicéntrico, aleatorizado, doble ciego, doble simulacro, de 3 brazos paralelos para comparar umeclidinio/vilanterol (62,5/25 microgramos [mcg], una vez al día), umeclidinio (62,5 mcg, una vez al día) y salmeterol (50 mg, dos veces al día) en sujetos masculinos y femeninos con EPOC. El objetivo principal de este estudio es demostrar mejoras en la función pulmonar en sujetos tratados con UMEC/VI en comparación con UMEC durante 24 semanas. Aproximadamente 2424 sujetos serán aleatorizados en 3 brazos paralelos en una proporción 1:1:1. Los sujetos serán estratificados según el uso de broncodilatadores de acción prolongada durante el período de rodaje (ninguno, uno o 2 broncodilatadores de acción prolongada por día). Los sujetos recibirán: UMEC/VI polvo para inhalación (62,5/25 mcg una vez al día) administrado mediante el inhalador de polvo seco (DPI) ELLIPTA® y placebo dos veces al día mediante DPI DISKUS®; o UMEC (62,5 mcg una vez al día) administrado mediante el DPI ELLIPTA y placebo dos veces al día mediante DPI DISKUS; o salmeterol (50 mcg dos veces al día [BID]) administrado mediante el DPI DISKUS y placebo una vez al día mediante DPI ELLIPTA. La duración del estudio será de 29 a 31 semanas, incluyendo un período de preselección de 2 semanas, un período de rodaje de 4 semanas, un período de tratamiento de 24 semanas y un período de seguimiento de 1 semana. ELLIPTA y DISKUS son marcas registradas del grupo de empresas GSK.

Elegibilidad

Edad mínima: 40 YearsSexo: ALL

Criterios de inclusión

years or older at date of signing informed consent at Screening Visit 1
Outpatient with a diagnosis of COPD
Persistent airflow limitations as indicated by a pre and post-albuterol/salbutamol FEV1/FVC ratio of \<0.70 and a post-albuterol/salbutamol FEV1 of \>=30% to \<=80% predicted normal values at Screening Visit 1.
A CAT score of \>=10 at Screening Visit 1
Current or former cigarette smokers with a history of cigarette smoking of \>=10 pack-years (number of pack years = \[number of cigarettes per day / 20\] multiplied by 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.
Male and female subjects are eligible to participate in the study. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin test), not lactating, and at least one of the following conditions applies: non-reproductive potential defined as pre-menopausal females with documented tubal ligation or documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or hysterectomy or documented bilateral oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases, a blood sample with simultaneous follicle stimulating hormone and estradiol levels consistent with menopause must be tested. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
A female subject with reproductive potential is eligible to participate if she is not pregnant and agrees to follow one of the highly effective methods for avoiding pregnancy in females of reproductive potential from 30 days prior to the first dose of study medication and until (at least five terminal half-lives or until any continuing pharmacologic effect has ended, whichever is longer) after the last dose of study medication and completion of the follow-up visit. The investigator is responsible for ensuring that subjects understand how to properly use methods of contraception.
Capable of giving signed informed consent prior to study participation.

Criterios de exclusión

A current diagnosis of asthma (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD, which is the primary cause of their respiratory symptoms).
Subjects with known alpha-antitrypsin deficiency as the underlying cause of COPD
Subjects with active tuberculosis are excluded. Subjects with other respiratory disorders (e.g., clinically significant: bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases) are excluded if these conditions are the primary cause of their respiratory symptoms.
Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease as per investigator assessment); stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis; chronic stable hepatitis B and C (e.g., presence of hepatitis B surface antigen or positive hepatitis C antibody test result or within 3 months prior to first dose of study treatment) are acceptable if subject otherwise meets entry criteria.
Subjects with unstable or life threatening cardiac disease. The investigational product should be used with caution in subjects with severe cardiovascular disease. In the opinion of the investigator, use will 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, or unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months, or New York Heart Association Class IV heart failure.
The investigator will determine the clinical significance of each abnormal electrocardiogram (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 or third degree heart block (unless pacemaker or defibrillator had been inserted).
Subjects with medical conditions such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction will be excluded unless, in the opinion of the study physician, the benefit outweighs the risk.
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 other condition (e.g., neurological condition) that is likely to affect respiratory function will not be included in the study.
Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1. Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 14 days prior to Screening Visit 1and at least 30 days following the last dose of oral/systemic corticosteroids (if applicable).
Subjects who had received inhaled corticosteroids (ICS) or ICS/ long-acting beta-agonist for the treatment of COPD in the 6 weeks prior to Screening Visit1.
Subjects who had \>1 moderate exacerbation in the 12 months prior to Screening Visit 1, or one severe exacerbation requiring hospitalization in the 12 months prior to Screening Visit 1.
Other respiratory tract infections that have not resolved at least 7 days prior to Screening Visit 1.
Subjects with lung volume reduction surgery (including procedures such as endobronchial valves) within the 12 months prior to Screening Visit 1.
Use of long-term oxygen therapy described as resting oxygen therapy \>3 Liter (L)/minute (min) at screening required to maintain adequate oxygenation (e.g., oxygen saturation in arterial blood \[SaO2\] \>90%; oxygen use \<=3 L/min flow is not exclusionary, and subjects may adjust oxygen levels up or down as needed during the study.)
Use of ICS within 6 weeks prior to Screening Visit 1; use of depot corticosteroids within 12 weeks prior to Screening Visit 1; use of systemic, oral or parenteral corticosteroids within 6 weeks prior to Screening Visit 1 (Localized corticosteroid injections \[e.g., intra-articular and epidural\] are permitted); use of antibiotics (for lower respiratory tract infection) within 6 weeks prior to Screening Visit 1; use of phosphodiesterase 4 (PDE4) inhibitor (e.g., roflumilast) within 14 days prior to Screening Visit 1; use of long-acting beta-agonist/ ICS combination products within 6 weeks prior to Screening Visit 1; use of theophyllines within 48 hours prior to Screening Visit 1; use of oral long-acting beta2-agonists within 48 hours and short-acting beta2-agonists within 12 hours prior to Screening Visit 1; use of inhaled short-acting beta2-agonists within 4 hours prior to Screening Visit 1 (use of study provided albuterol/salbutamol is permitted during the study, except in the 4-hour period prior to spirometry testing); use of inhaled short-acting anticholinergics within 4 hours prior to Screening Visit 1; use of inhaled short-acting anticholinergic/short-acting beta2-agonist combination products within 4 hours prior to Screening Visit 1; use of any other investigational medication within 30 days or within 5 drug half-lives (whichever is longer) prior to Screening Visit 1.
Subject unable to withhold albuterol/salbutamol for the 4-hour period required prior to spirometry testing at each study visit.
Regular use (prescribed for daily/ regular use, not for as-needed use) of short-acting bronchodilators (e.g., albuterol/salbutamol).
A known or suspected history of alcohol or drug abuse within 2 years prior to Screening Visit 1 that in the opinion of the investigator would prevent the subject from completing the study procedures.
Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, sympathomimetic, lactose/milk protein or magnesium stearate.
Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
Subject 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.
In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete questionnaires on the electronic diary.

Intervenciones

drug

UMEC/VI 62.5/25 mcg via ELLIPTA

ELLIPTA DPI inhaler will contain two individual blister strips with 30 blisters per strip; the first strip contains umeclidinium bromide (62.5 mcg per blister) blended with lactose monohydrate and magnesium stearate and second strip contains vilanterol trifenatae (25 mcg per blister) blended with lactose monohydrate and magnesium stearate.

drug

UMEC 62.5 mcg via ELLIPTA

The ELLIPTA inhaler will contain one blister strip, which will have 30 blisters of umeclidinium bromide (62.5 mcg).

drug

Salmeterol 50 mcg via DISKUS

The DISKUS inhaler will contain one blister strip, which will have 60 blisters of salmeterol xinafoate (50 mcg). The DISKUS will provide a total of 60 doses (60 blisters) and will deliver, when actuated, the contents of a single blister strip.

drug

Placebo via ELLIPTA

Lactose dry powder will be administered using ELLIPTA for both treatment periods. ELLIPTA DPI inhaler will contain two individual blister strips with 30 blisters per strip; containing lactose dry powder.

drug

Placebo via DISKUS

Lactose dry powder will be administered using DISKUS for both treatment periods. The DISKUS inhaler will contain one blister strip, which will have 60 blisters of lactose dry powder. The DISKUS will provide a total of 60 doses (60 blisters) and will deliver, when actuated, the contents of a single blister strip.

Ubicaciones

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Florida, Buenos Aires, Argentina

GSK Investigational Site

La Plata, Buenos Aires, Argentina

GSK Investigational Site

Lobos, Buenos Aires, Argentina

GSK Investigational Site

Mar del Plata, Buenos Aires, Argentina

GSK Investigational Site

Mar del Plata, Buenos Aires, Argentina

GSK Investigational Site

Paraná, Buenos Aires, Argentina

GSK Investigational Site

Quilmes, Buenos Aires, Argentina

GSK Investigational Site

Vicente López, Buenos Aires, Argentina

GSK Investigational Site

Córdoba, Córdoba Province, Argentina

GSK Investigational Site

Concepción del Uruguay, Entre Ríos Province, Argentina

GSK Investigational Site

San Rafael, Mendoza Province, Argentina

GSK Investigational Site

Rosario, Santa Fe Province, Argentina

GSK Investigational Site

Rosario, Santa Fe Province, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Capital Federal, Argentina

GSK Investigational Site

Ciudad Autonoma de Buenis Aires, Argentina

GSK Investigational Site

Mendoza, Argentina

GSK Investigational Site

Mendoza, Argentina

GSK Investigational Site

Mendoza, Argentina

GSK Investigational Site

Monte Grande, Argentina

GSK Investigational Site

San Miguel de Tucumán, Argentina

GSK Investigational Site

San Miguel de Tucumán, Argentina

GSK Investigational Site

Santa Fe, Argentina

GSK Investigational Site

Santa Rosa, Argentina

Estudio de tratamiento de 24 semanas, multicéntrico, aleatorizado, doble ciego, doble simulacro, de grupos paralelos para comparar umeclidinio/vilanterol, umeclidinio y salmeterol en sujetos con enfermedad pulmonar obstructiva crónica (EPOC)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

UMEC/VI 62.5/25 mcg via ELLIPTA

UMEC 62.5 mcg via ELLIPTA

Salmeterol 50 mcg via DISKUS

Placebo via ELLIPTA

Placebo via DISKUS

Ubicaciones

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

Patrocinadores