A Phase IIIb Study to Evaluate the Efficacy of Umeclidinium/Vilanterol (UMEC/VI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

NCT02152605 | Completed Phase 3 Results

• 1 other identifier: 201211
• Study Type: interventional
• Target: 498
• Locations: 7 countries
• Sites: 54

Brief Summary

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

SGRQ; vilanterol; long-acting beta2-agonist; long-acting muscarinic antagonist; COPD; umeclidinium

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Mean St.George's Respiratory Questionnaire (SGRQ) Total Score at Day 84

  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.

  Baseline and Day 84

Secondary Outcomes (2)

• Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 84

  Baseline and Day 84

• Change From Baseline (BL) in Mean Number of Puffs of Rescue Medication Per Day Used Over Weeks 1-12

  Week 1 amd Week 12

Study Arms (2)

Umeclidinium/Vilanterol 62.5/25 mcg once daily

EXPERIMENTAL

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)

Drug: UMEC/VI

Placebo once daily

PLACEBO COMPARATOR

The subjects will receive placebo, administered as one inhalation once-daily in the morning via a DPI

Drug: Placebo

Interventions

UMEC/VI DRUG

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

Umeclidinium/Vilanterol 62.5/25 mcg once daily

Placebo DRUG

Dry white powder delivered via DPI (2 strips with 30 blisters each, both containing lactose with magnesium stearate), administered as one inhalation of placebo

Placebo once daily

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
• Asthma: A current diagnosis of asthma.
• 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.
• 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 \[whichever is longer\])
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (54)

GSK Investigational Site

Phoenix, Arizona, 85006, United States

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GSK Investigational Site

Upland, California, 91786, United States

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GSK Investigational Site

Clearwater, Florida, 33765-2616, United States

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GSK Investigational Site

Saint Charles, Missouri, 63301, United States

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GSK Investigational Site

Anderson, South Carolina, 29621, United States

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GSK Investigational Site

Easley, South Carolina, 29640, United States

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GSK Investigational Site

Mt. Pleasant, South Carolina, 29464, United States

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GSK Investigational Site

Rock Hill, South Carolina, 29732, United States

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GSK Investigational Site

Seneca, South Carolina, 29678, United States

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GSK Investigational Site

Union, South Carolina, 29379, United States

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GSK Investigational Site

San Antonio, Texas, 78229, United States

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GSK Investigational Site

Dupnitsa, 2600, Bulgaria

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GSK Investigational Site

Gabrovo, 5300, Bulgaria

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GSK Investigational Site

Kyustendil, 2500, Bulgaria

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GSK Investigational Site

Montana, Bulgaria

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GSK Investigational Site

Sevlievo, 5400, Bulgaria

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GSK Investigational Site

Sliven, 8800, Bulgaria

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GSK Investigational Site

Sofia, 1336, Bulgaria

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GSK Investigational Site

Kassel, Hesse, 34121, Germany

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GSK Investigational Site

Weyhe-Leeste, Lower Saxony, 28844, Germany

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GSK Investigational Site

Reinfeld, Schleswig-Holstein, 23858, Germany

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GSK Investigational Site

Berlin, 10119, Germany

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GSK Investigational Site

Berlin, 10629, Germany

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GSK Investigational Site

Berlin, 10717, Germany

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GSK Investigational Site

Hamburg, 22143, Germany

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GSK Investigational Site

Balassagyarmat, 2660, Hungary

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GSK Investigational Site

Budaörs, 2040, Hungary

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GSK Investigational Site

Budapest, 1085, Hungary

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GSK Investigational Site

Debrecen, 4032, Hungary

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GSK Investigational Site

Gödöllő, 2100, Hungary

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GSK Investigational Site

Nyíregyháza, 4400, Hungary

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GSK Investigational Site

Szeged, 6722, Hungary

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GSK Investigational Site

Szikszó, 3800, Hungary

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GSK Investigational Site

Cluj-Napoca, 400371, Romania

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GSK Investigational Site

Codlea, 505100, Romania

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GSK Investigational Site

Craiova, 200642, Romania

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GSK Investigational Site

Deva, 330084, Romania

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GSK Investigational Site

Iași, 700115, Romania

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GSK Investigational Site

Piteşti, 110084, Romania

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GSK Investigational Site

Moscow, 117997, Russia

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GSK Investigational Site

Novosibirsk, 630099, Russia

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GSK Investigational Site

Saint Petersburg, 194356, Russia

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GSK Investigational Site

Saint Petersburg, 198216, Russia

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GSK Investigational Site

Saint Petesburg, 195030, Russia

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GSK Investigational Site

Sestroretsk, 197706, Russia

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GSK Investigational Site

Stavropol, 355017, Russia

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GSK Investigational Site

Ulyanovsk, 432063, Russia

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GSK Investigational Site

Voronezh, 394018, Russia

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GSK Investigational Site

Yekaterinburg, 620039, Russia

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GSK Investigational Site

Kharkiv, 61002, Ukraine

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GSK Investigational Site

Kharkiv, 61124, Ukraine

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GSK Investigational Site

Kiev, 03680, Ukraine

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GSK Investigational Site

Kyiv, 01114, Ukraine

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GSK Investigational Site

Kyiv, 02232, Ukraine

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2014
• First Posted: June 2, 2014
• Study Start: September 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 5, 2015
• Last Updated: November 9, 2017
• Results First Posted: February 25, 2016

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

HU (8); RO (6); BU (7); RU (10); US (11); DE (7); UA (5)