A 12-week Study to Evaluate the Efficacy and Safety of Umeclidinium Compared With Tiotropium in Subjects With Chronic Obstructive Pulmonary Disease

NCT ID: NCT02207829

Last Updated: 2018-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1017 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-01
• Study Completion Date: 2015-06-15

Brief Summary

This is a multicentre, randomized, blinded, double dummy, parallel group study to evaluate the efficacy and safety of UMEC inhalation powder[ (62.5 microgram (mcg) once daily (QD)] when administered via a novel Dry Powder Inhaler compared with tiotropium (18 mcg QD) administered via a HANDIHALER® inhaler over a treatment period of 12 weeks (24 weeks in Germany) in subjects with chronic obstructive pulmonary disease (COPD). At the end of the run-in period, subjects who meet the randomization criteria will be randomized to receive UMEC 62.5 mcg administered via novel dry powder inhaler(nDPI) + Placebo administered via HANDIHALER inhaler OR Tiotropium 18 mcg administered via HANDIHALER inhaler + Placebo administered via nDPI in a 1:1 ratio. There will be up to 8 clinic visits conducted on an outpatient basis at Pre-Screening (Visit 0), Screening (Visit 1), a 7 to 14 day run-in period, 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). For subjects enrolled in Germany, there will be an additional 3 visits at Day 112 (Visit 8), Day 140 (Visit 9) and Day 168 (Visit 10). The total duration of subject participation in the study will be approximately 15 weeks (27 weeks in Germany). The primary endpoint of the study is clinic visit trough forced expiratory volume in one second (FEV1) 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 blinded study medication at Visits 3 to 7.

HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH & Co. KG.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Umeclidinium 62.5 mcg + placebo

Subjects will receive UMEC Inhalation Powder 62.5 mcg once daily via nDPI plus placebo once daily via HANDIHALER inhaler for 12 weeks (24 weeks in Germany). Subjects will be instructed to take one inhalation each morning from both the nDPI and the HANDIHALER inhaler

Group Type: EXPERIMENTAL

Umeclidinium

Intervention Type: DRUG

Umeclidinium 62.5 mcg once daily in the morning via nDPI

Umeclidinium matching placebo

Intervention Type: DRUG

Umeclidinium matching placebo once daily in the morning via nDPI

Tiotropium 18mcg + placebo

Subjects will receive Tiotropium 18 mcg once daily via HANDIHALER inhaler plus placebo once daily via nDPI for 12 weeks (24 weeks in Germany). Subjects will be instructed to take one inhalation each morning from both the nDPI and the HANDIHALER inhaler

Group Type: ACTIVE_COMPARATOR

Tiotropium

Intervention Type: DRUG

Tiotropium 18 mcg once daily in the morning via HANDIHALER inhaler

Tiotropium matching placebo

Intervention Type: DRUG

Tiotropium matching placebo once daily in the morning via HANDIHALER inhaler

Interventions

Umeclidinium

Umeclidinium 62.5 mcg once daily in the morning via nDPI

Intervention Type: DRUG

Umeclidinium matching placebo

Umeclidinium matching placebo once daily in the morning via nDPI

Intervention Type: DRUG

Tiotropium

Tiotropium 18 mcg once daily in the morning via HANDIHALER inhaler

Intervention Type: DRUG

Tiotropium matching placebo

Tiotropium matching placebo once daily in the morning via HANDIHALER inhaler

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, 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 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

• 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 >=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.
• French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

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.
• Moderate to severe Renal Impairment: Patients with moderate to 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 (LAMAs) 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 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 ; long-acting beta2-agonists/inhaled corticosteroids (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 [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 mcg/day of FP or equivalent- 30 days; Initiation or discontinuation of ICS use-30 days (Use of ICS is permitted provided the dose does not exceed 1000mcg 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; Inhaled long acting beta2 agonists (LABAs): salmeterol, formoterol-48 hours, olodaterol, indacaterol, vilanterol- 14 days; LAMAs: 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 (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 write 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

Spartanburg, South Carolina, United States

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Winnipeg, Manitoba, Canada

GSK Investigational Site

St. John's, Newfoundland and Labrador, Canada

GSK Investigational Site

Truro, Nova Scotia, Canada

GSK Investigational Site

Greater Sudbury, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Saint-Charles-Borromée, Quebec, Canada

GSK Investigational Site

Sherbrooke, Quebec, Canada

GSK Investigational Site

Valparaíso, Región de Valparaíso, 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

Talcahuano, , Chile

GSK Investigational Site

Aarhus C, , Denmark

GSK Investigational Site

Hvidovre, , Denmark

GSK Investigational Site

København NV, , Denmark

GSK Investigational Site

Odense, , Denmark

GSK Investigational Site

Bletterans, , France

GSK Investigational Site

Nantes, , France

GSK Investigational Site

Toulon, , France

GSK Investigational Site

Tours, , France

GSK Investigational Site

Vieux-Condé, , France

GSK Investigational Site

Aschaffenburg, Bavaria, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Neu-Isenburg, Hesse, Germany

GSK Investigational Site

Rodgau, Hesse, Germany

GSK Investigational Site

Wiesbaden, Hesse, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Teuchern, Saxony-Anhalt, Germany

GSK Investigational Site

Schmölln, Thuringia, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Riccione (RN), Emilia-Romagna, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Torrette (AN), The Marches, Italy

GSK Investigational Site

Pisa, Tuscany, Italy

GSK Investigational Site

Negrar, Veneto, Italy

GSK Investigational Site

Bacau, , Romania

GSK Investigational Site

Brăila, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Codlea, , Romania

GSK Investigational Site

Comuna Alexandru Cel Bun, , Romania

GSK Investigational Site

Deva, , Romania

GSK Investigational Site

Focşani, , Romania

GSK Investigational Site

Galati, , Romania

GSK Investigational Site

Ploieşti, , Romania

GSK Investigational Site

Timișoara, , Romania

GSK Investigational Site

Arkhangelsk, , Russia

GSK Investigational Site

Arkhangelsk, , Russia

GSK Investigational Site

Barnaul, , Russia

GSK Investigational Site

Irkutsk, , Russia

GSK Investigational Site

Izhevsk, , Russia

GSK Investigational Site

Kemerovo, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Novosibirsk, , 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 Petersburg, , Russia

GSK Investigational Site

Sestroretsk, , Russia

GSK Investigational Site

Sochi, , Russia

GSK Investigational Site

Stavropol, , Russia

GSK Investigational Site

Tomsk, , Russia

GSK Investigational Site

Ufa, , Russia

GSK Investigational Site

Vladimir, , Russia

GSK Investigational Site

Port Elizabeth, Eastern Cape, South Africa

GSK Investigational Site

Boksburg, Gauteng, South Africa

GSK Investigational Site

Bellville, , South Africa

GSK Investigational Site

Durban, , South Africa

GSK Investigational Site

Korsten, , South Africa

GSK Investigational Site

Lynnwood Ridge, Pretoria, , South Africa

GSK Investigational Site

Mowbray, , South Africa

GSK Investigational Site

Somerset West, , South Africa

GSK Investigational Site

Vrededorp, , South Africa

GSK Investigational Site

Welkom, , South Africa

GSK Investigational Site

Bucheon-Si, Gyeonggi-Do, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Wonju-si, Gangwon-do, , South Korea

GSK Investigational Site

Dnipropetrovsk, , Ukraine

GSK Investigational Site

Kharkiv, , Ukraine

GSK Investigational Site

Kharkiv, , Ukraine

GSK Investigational Site

Kiev, , Ukraine

GSK Investigational Site

Kryvyi Rig, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Poltava, , Ukraine

GSK Investigational Site

Zaporizhzhia, , Ukraine

Countries

United States; Argentina; Canada; Chile; Denmark; France; Germany; Italy; Romania; Russia; South Africa; South Korea; Ukraine

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)

Feldman G, Maltais F, Khindri S, Vahdati-Bolouri M, Church A, Fahy WA, Trivedi R. A randomized, blinded study to evaluate the efficacy and safety of umeclidinium 62.5 mug compared with tiotropium 18 mug in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2016 Apr 7;11:719-30. doi: 10.2147/COPD.S102494. eCollection 2016.

Reference Type: DERIVED

PMID: 27103795 (View on PubMed)

Study Documents

Document Type: Clinical Study Report

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

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Document Type: Annotated Case Report Form

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

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Document Type: Statistical Analysis Plan

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

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Document Type: Study Protocol

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

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Document Type: Dataset Specification

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: Informed Consent Form

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

View Document

Related Links

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Other Identifiers

201316

Identifier Type: -

Identifier Source: org_study_id