A 12-week Study to Evaluate the Efficacy and Safety of Umeclidinium 62.5 Microgram (mcg) Compared With Glycopyrronium 44 mcg in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

NCT ID: NCT02236611

Last Updated: 2018-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1036 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-26
• Study Completion Date: 2015-06-02

Brief Summary

This is a 12-week, multicentre, randomized, open-label, 2-arm, parallel-group study designed to compare the efficacy and safety of umeclidinium inhalation powder (62.5 mcg once daily [QD]) administered via a novel Dry Powder Inhaler (nDPI) with glycopyrronium (44 mcg QD) administered via a Breezhaler® inhaler in subjects with COPD over 12 weeks of treatment. At the end of the run-in period, eligible subjects will be randomized in a 1:1 ratio to receive umeclidinium 62.5 mcg administered via nDPI or glycopyrronium 44 mcg administered via BREEZHALER inhaler. There will be up to 8 clinic visits conducted on an outpatient basis at Pre-Screening (Visit 0), Screening (Visit 1), Randomization at Day 1 (Visit 2), and after Randomization at Day 2 (Visit 3), Day 28 (Visit 4), Day 56 (Visit 5), Day 84 (Visit 6) and Day 85 (Visit 7). The total duration of subject participation in the study will be approximately 15 weeks. The primary endpoint of the study is clinic visit trough FEV1 (forced expiratory volume in one second) on treatment Day 85. All subjects will have spirometry performed at clinic Visits 1 though 7. Trough spirometry will be obtained 23 and 24 hours after the previous day's dose of open-label study medication at Visits 3 to 7.

BREEZHALER is a registered trademark of Novartis AG.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Umeclidinium 62.5 mcg

Randomized subjects will receive umeclidinium inhalation powder 62.5 mcg, once daily over a period of 12 weeks via a nDPI. Subjects will be instructed to take one dose each morning.

Group Type: EXPERIMENTAL

Umeclidinium

Intervention Type: DRUG

Umeclidinium 62.5 mcg will be available as dry inhalation powder to be taken using a nDPI

Glycopyrronium 44 mcg

Randomized subjects will receive glycopyrronium 44 mcg, once daily over a period of 12 weeks via a BREEZHALER inhaler. Subjects will be instructed to take one dose each morning.

Group Type: EXPERIMENTAL

Glycopyrronium

Intervention Type: DRUG

Glycopyrronium bromide will be available as inhalation capsules, 44 mcg per capsule, taken using BREEZHALER inhalers

Interventions

Umeclidinium

Umeclidinium 62.5 mcg will be available as dry inhalation powder to be taken using a nDPI

Intervention Type: DRUG

Glycopyrronium

Glycopyrronium bromide will be available as inhalation capsules, 44 mcg per capsule, taken using BREEZHALER inhalers

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Type of subject: outpatient
• Informed Consent: a signed and dated written informed consent prior to study participation
• Age: subjects 40 years of age or older at Visit 1.
• Gender: male and female subjects are eligible to participate in the study. A female 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, eg, 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 acceptable contraceptive methods used consistently and correctly i.e., in accordance with the approved product label and the instructions of the physician for the duration of the study - screening to follow-up contact.
• Diagnosis: an established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society (ERS)
• 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 (eg. 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 forced expiratory volume in one second/ forced vital capacity (FEV1/FVC ratio of <0.70 and a post-albuterol/salbutamol FEV1 of >=30% and =<70% of predicted normal values at Visit 1. Predicted values will be based upon the ERS Global Lung Function Initiative
• Dyspnea: A score of >=2 on the modified medical research council dyspnea scale (mMRC) 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.
• Severe renal impairment: patients with severe renal impairment (e.g., end-stage renal disease requiring dialysis) should be excluded, unless in the opinion of the investigator, the benefit is likely to outweigh the risk.
• Unstable or life threatening cardiac disease: long-acting muscarinic antagonists (LAMA) 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, 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; sustained or nonsustained ventricular tachycardia; second degree heart block Mobitz type II or 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.
• 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, inhaled long acting beta2 agonists/ inhaled corticosteroid (LABA/ICS) combination products if LABA/ICS therapy is discontinued completely 30 days; LABA/ICS combination products only If discontinuing ICS/ LABA therapy and switching to ICS monotherapy 48 hours for the salmeterol or formoterol component 14 days for the vilanterol component (note: the dose of ICS must be a dose of fluticasone propionate (FP) or equivalent but not to exceed 1000 mcg/day), use of ICS at a dose >1000 microgram (mcg)/day of FP or equivalent 30 days (note: use of ICS is permitted provided the dose does not exceed 1000 mcg of FP or equivalent; ICS use not to be initiated or discontinued within 30 days prior to Visit 1, except for subjects on LABA/ICS therapy who may discontinue the ICS/LABA product as indicated in the table above and switch to ICS monotherapy); initiation or discontinuation of ICS use 30 days (note: use of ICS is permitted provided the dose does not exceed 1000 mcg of FP or equivalent; ICS use not to be initiated or discontinued within 30 days prior to Visit 1, except for subjects on LABA/ICS therapy who may discontinue the ICS/LABA product as indicated in the table above and switch to ICS monotherapy); phosphodiesterase 4 (PDE4) Inhibitor (roflumilast) 14 days; LABA: salmeterol and formoterol 48 hours; olodaterol, indacaterol, and vilanterol 14 days; LAMA: tiotropium, aclidinium, glycopyrronium, umeclidinium 7 days; LAMA/LABA combination products if LAMA/LABA therapy is discontinued completely then 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 (note: use of study provided albuterol/salbutamol is permitted during the study, except in the 4-hour period prior to spirometry testing); 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.
• Nebulized therapy: regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g. albuterol/salbutamol) via nebulized 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Paraná, Buenos Aires, 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

Mendoza, , Argentina

GSK Investigational Site

Mendoza, , Argentina

GSK Investigational Site

San Miguel de Tucumán, , Argentina

GSK Investigational Site

San Miguel de Tucumán, , Argentina

GSK Investigational Site

Talca, Maule Region, Chile

GSK Investigational Site

Concepción, Región Del Biobio, Chile

GSK Investigational Site

Puente Alto - Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Santiago, , Chile

GSK Investigational Site

Santiago, , Chile

GSK Investigational Site

Jindřichův Hradec, , Czechia

GSK Investigational Site

Kralupy nad Vltavou, , Czechia

GSK Investigational Site

Lovosice, , Czechia

GSK Investigational Site

Ostrava - Poruba, , Czechia

GSK Investigational Site

Rudna U Prahy, , Czechia

GSK Investigational Site

Třebíč, , Czechia

GSK Investigational Site

Varnsdorf, , Czechia

GSK Investigational Site

Bamberg, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Brinkum/Stuhr, Lower Saxony, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Düren, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Gelsenkirchen, North Rhine-Westphalia, Germany

GSK Investigational Site

Koblenz, Rhineland-Palatinate, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Lübeck, Schleswig-Holstein, Germany

GSK Investigational Site

Balassagyarmat, , Hungary

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Debrecen, , Hungary

GSK Investigational Site

Debrecen, , Hungary

GSK Investigational Site

Kapuvár, , Hungary

GSK Investigational Site

Nagykanizsa, , Hungary

GSK Investigational Site

Törökbálint, , Hungary

GSK Investigational Site

Ålesund, , Norway

GSK Investigational Site

Hakadal, , Norway

GSK Investigational Site

Hamar, , Norway

GSK Investigational Site

Hønefoss, , Norway

GSK Investigational Site

Kolbjørnsvik, , Norway

GSK Investigational Site

Kongsvinger, , Norway

GSK Investigational Site

Løvenstad, , Norway

GSK Investigational Site

Brasov, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Cluj-Napoca, , Romania

GSK Investigational Site

Iași, , Romania

GSK Investigational Site

Râmnicu Vâlcea, , Romania

GSK Investigational Site

Suceava, , Romania

GSK Investigational Site

Timișoara, , Romania

GSK Investigational Site

Barnaul, , Russia

GSK Investigational Site

Barnaul, , Russia

GSK Investigational Site

Chelyabinsk, , Russia

GSK Investigational Site

Chelyabinsk, , Russia

GSK Investigational Site

Chelyabinsk, , Russia

GSK Investigational Site

Chita, , Russia

GSK Investigational Site

Irkutsk, , Russia

GSK Investigational Site

Ivanovo, , Russia

GSK Investigational Site

Kazan', , Russia

GSK Investigational Site

Kemerovo, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Nizhny Novgorod, , Russia

GSK Investigational Site

Novosibirsk, , Russia

GSK Investigational Site

Perm, , Russia

GSK Investigational Site

Ryazan, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petesburg, , Russia

GSK Investigational Site

Stavropol, , Russia

GSK Investigational Site

Yekaterinburg, , Russia

GSK Investigational Site

Laredo, Cantabria, Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Fuenlabrada / Madrid, , Spain

GSK Investigational Site

La Roca Del Valles (Barcelona), , Spain

GSK Investigational Site

Peralada( Girona), , Spain

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Stockholm, , Sweden

GSK Investigational Site

Stockholm, , Sweden

Countries

Argentina; Chile; Czechia; Germany; Hungary; Norway; Romania; Russia; Spain; Sweden

References

Shah D, Driessen M, Risebrough N, Baker T, Naya I, Briggs A, Ismaila AS. Cost-effectiveness of umeclidinium compared with tiotropium and glycopyrronium as monotherapy for chronic obstructive pulmonary disease: a UK perspective. Cost Eff Resour Alloc. 2018 May 10;16:17. doi: 10.1186/s12962-018-0101-3. eCollection 2018.

Reference Type: DERIVED

PMID: 29773969 (View on PubMed)

Rheault T, Khindri S, Vahdati-Bolouri M, Church A, Fahy WA. A randomised, open-label study of umeclidinium versus glycopyrronium in patients with COPD. ERJ Open Res. 2016 Apr 27;2(2):00101-2015. doi: 10.1183/23120541.00101-2015. eCollection 2016 Apr.

Reference Type: DERIVED

PMID: 27730198 (View on PubMed)

Study Documents

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

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Other Identifiers

201315

Identifier Type: -

Identifier Source: org_study_id