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Pulmonary Disease, Chronic ObstructivePhase 4NCT02257372

A Study to Evaluate the Effect of Umeclidinium (UMEC) as Combination Therapy in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

A Phase 4 study testing UMEC DPI, ICS/LABA medication and Albuterol/salbutamol Metered Dose Inhaler (MDI) in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 28 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multicenter, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of the addition of UMEC (62.5 microgram[mcg]) when administered once-daily via dry powder inhaler (DPI) to Inhaled corticosteroid/ Long-acting beta2-agonist (ICS/LABA) twice-daily compared with placebo via DPI… Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Pulmonary Disease, Chronic Obstructive
What is being tested?
UMEC DPI, ICS/LABA medication and Albuterol/salbutamol Metered Dose Inhaler (MDI)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
236 participants
Where
28 sitesin 4 countries
Study dates
30 Sep 2014to 24 Mar 2015
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 following 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): 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 Standard Operating Procedure (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, and this male is the sole partner for that subject. For this definition, "documented" refers to the outcome of the investigator's/designee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records; 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)]. 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.
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  • 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 post-albuterol/salbutamol FEV1 of <=70% of predicted normal values at Visit 1 (Screening) calculated using reference values provided by Quanjer.
  • Current clinically prescribed medication: The subject must be on the dose and frequency of one of the following ICS/LABA combinations approved for COPD at least 30 days prior screening : FSC at a dose of 500/50 mcg twice-daily (i.e. SERETIDE DISKUS™ inhaler or approved generic product such as AIRFLUSAL FORSPIRO inhaler 500/50 mcg twice daily or ROLENIUM ELPENHALER inhaler 500/50 mcg twice daily) ; The combination of budesonide/formoterol (i.e., SYMBICORT TURBUHALER inhaler) at doses of 200/6 mcg twice-daily or 400/12 mcg twice-daily .
  • Dyspnea: A score of >=2 on the Modified Medical Research Council (mMRC) Dyspnea Scale at Visit 1.

Who cannot join

  • 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: The subject is considered unlikely to survive the duration of the study period or has any rapidly progressing disease or immediately life-threatening illness e.g. cancer.
  • Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, sympathomimetic, corticosteroid (intranasal, inhaled or systemic) lactose/milk protein or magnesium stearate.
  • Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
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  • Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit 1.
  • Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1.
  • Unstable or life threatening cardiac disease: UMEC 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
  • 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 Principle 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 nonsustained ventricular tachycardia; Second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator had been inserted)
  • Antimuscarinic effects: Subjects with medical conditions such as narrow-angle glaucoma, prostatic hypertrophy, or bladder neck obstruction should only be included if, in the opinion of the study physician, the benefit outweighs the risk.
  • 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.
  • 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.
  • 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); CYP3A4 strong inhibitors (6 weeks) ; ICS /LABA combination products except SERETIDE and approved FSC 500/50 generic products and SYMBICORT at approved doses and frequencies for COPD (30 days) ; SERETIDE, approved FSC 500/50 generic products, and SYMBICORT at approved doses and frequencies for COPD (12 hours prior to screening); Phosphodiesterase 4 (PDE4) Inhibitor (roflumilast) (14 days); Long-acting muscarinic antagonists (tiotropium, aclidinium, glycopyrronium, UMEC) (7 days); Inhaled long acting beta2 agonists (LABA) (salmeterol, formoterol: 48 hrs) olodaterol, indacaterol (14 days); LAMA/LABA combination products (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). Note: Use of study provided albuterol/salbutamol is permitted during the study, except in the 4-hour period prior to spirometry testing. Intra-articular and epidural corticosteroid injections are permitted. Corticosteroids for short term treatment of COPD exacerbations is allowed
  • 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, or who will enter the acute phase of a pulmonary rehabilitation program during the study. 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: A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, subinvestigator, study coordinator, or employee of the participating investigator.
  • 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.
  • DISKUS is a trade mark of the GlaxoSmithKline Group of Companies. Other company or product names mentioned herein may be the property of their respective owners.

Trial locations and contacts

28 sites in 4 countries.

28 sites in 4 countries

Germany10 sites

  • GSK Investigational Site

    Berlin, 10629

  • GSK Investigational Site

    Berlin, 13125

  • GSK Investigational Site

    Berlin, 14059

  • GSK Investigational Site

    Cologne, North Rhine-Westphalia, 51069

  • GSK Investigational Site

    Dillingen an der Donau, Bavaria, 89407

  • GSK Investigational Site

    Essen, North Rhine-Westphalia, 45355

  • GSK Investigational Site

    Frankfurt am Main, Hesse, 60596

  • GSK Investigational Site

    Goch, North Rhine-Westphalia, 47574

  • GSK Investigational Site

    Munich, Bavaria, 80339

  • GSK Investigational Site

    Potsdam, Brandenburg, 14467

Other trials in Germany

Greece7 sites

  • GSK Investigational Site

    Athens, 115 27

  • GSK Investigational Site

    Heraklion, Crete, 71110

  • GSK Investigational Site

    Kavala, 65500

  • GSK Investigational Site

    N. Efkarpia, Thessaloniki, 564 29

  • GSK Investigational Site

    Rethymnon, Crete, 74100

  • GSK Investigational Site

    Thessaloniki, 56403

  • GSK Investigational Site

    Thessaloniki, 57010

Other trials in Greece

Netherlands6 sites

  • GSK Investigational Site

    Almelo, 7609 PP

  • GSK Investigational Site

    Breda, 4818 CK

  • GSK Investigational Site

    Eindhoven, 5623 EJ

  • GSK Investigational Site

    Harderwijk, 3844 DG

  • GSK Investigational Site

    Hoorn, 1624 NP

  • GSK Investigational Site

    Kloosterhaar, 7694 AC

Other trials in Netherlands

Czechia5 sites

  • GSK Investigational Site

    Kuřim, 66434

  • GSK Investigational Site

    Olomouc, 772 00

  • GSK Investigational Site

    Rokycany, 337 01

  • GSK Investigational Site

    Teplice, 415 10

  • GSK Investigational Site

    Žatec, 438 01

Other trials in Czechia

About this study

Official title: A Randomized, Parallel Group Study to Evaluate the Effect of Umeclidinium (UMEC) Added to Inhaled Corticosteroid/ Long-acting Beta-agonist Combination Therapy in Subjects With Chronic Obstructive Pulmonary Disease COPD

This is a multicenter, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of the addition of UMEC (62.5 microgram[mcg]) when administered once-daily via dry powder inhaler (DPI) to Inhaled corticosteroid/ Long-acting beta2-agonist (ICS/LABA) twice-daily compared with placebo via DPI added to the ICS/LABA therapy over a treatment period of 12 weeks in subjects with COPD. This study is designed to investigate the addition of UMEC to ICS/LABA combinations at approved doses and frequencies for the treatment of COPD including SERETIDE™ 500/50 mcg twice daily, Fluticasone Propionate/Salmeterol Combination (FSC) 500/50 twice daily generic products such as AIRFLUSAL FORSPIRO inhaler 500/50 mcg twice daily or ROLENIUM ELPENHALER inhaler 500/50 mcg twice daily and SYMBICORT TURBUHALER inhaler at doses of 200/6 mcg twice daily and 400/12 mcg twice daily, over 12 weeks in subjects with COPD. Albuterol/salbutamol metered-dose-inhaler (MDI) or nebules will be issued throughout the study for use as-needed (prn).

Subjects who meet the eligibility criteria will be randomly assigned to one of the following blinded study treatment regimens in equal proportion (1:1): UMEC 62.5 mcg once-daily and Placebo once-daily. Approximately 230 subjects (115 subjects per treatment) will be randomized in order to complete at least 206 evaluable subjects. The total duration of the study will be approximately 14 weeks for each subject.

Read more

UMEC is a Long-acting Muscarinic Antagonist (LAMA) currently under development as a monotherapy, as a combination product with a LABA, vilanterol (VI), for the treatment of COPD, and as a combination product with an ICS, fluticasone furoate (FF), for the treatment of asthma. The UMEC/VI combination 62.5/25 .mcg once-daily has been approved in the United States (U.S.) and Canada for COPD under the trade name ANORO™ ELLIPTA™ and is under regulatory review in other countries.

SERETIDE, ANORO, and ELLIPTA are trade marks of the GlaxoSmithKline Group of Companies. Other company or product names mentioned herein may be the property of their respective owners.

Being tested
UMEC DPI, Placebo DPI, ICS/LABA medication, Albuterol/salbutamol Metered Dose Inhaler (MDI)
Keywords
FEV1, DPI, ICS/LABA, UMEC, COPD
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • UMEC DPIDrug

    The UMEC DPI will contain one blister strip which will have 30 blisters of UMEC as dry powder blended with lactose and magnesium stearate, with no companion strip. Each actuation of the DPI will deliver the contents of one blister from each strip simultaneously.

  • Placebo DPIDrug

    The matching placebo DPI, identical in appearance to the inhaler containing active study medication, will have two blister strips, each containing 30 blisters of lactose and magnesium stearate.

  • ICS/LABA medicationDrug

    Participants will use ICS/LABA combinations that are approved for the treatment of COPD at approved doses and frequency including SERETIDE 500/50mcg twice daily, FSC 500/50 mcg twice daily generic products such as AIRFLUSAL FORSPIRO inhaler 500/50mcg twice daily or ROLENIUM ELPENHALER inhaler 500/50mcg twice daily and SYMBICORT TURBUHALER inhaler at doses of 200/6mcg twice daily and 400/12mcg twice daily. The ICS/LABA will be sourced from local commercial stock while on the study

  • Albuterol/salbutamol Metered Dose Inhaler (MDI)Drug

    Albuterol/salbutamol MDI or nebules will be issued throughout the study as rescue medication, for use as-needed. Albuterol/salbutamol will be sourced from local commercial stock or provided centrally from GlaxoSmithKline.

Study groups in NCT02257372
Study groupRoleWhat they receive
UMEC (62.5 mcg)ExperimentalParticipants will self-administer blinded UMEC (62.5 mcg) each morning (once daily) as one inhalation from the double-blind DPI over a treatment period of 12 weeks. Participants will receive open labeled ICS/LABA medication through out duration of the treatment period as background treatment.
Receives: Drug: UMEC DPI; Drug: ICS/LABA medication; Drug: Albuterol/salbutamol Metered Dose Inhaler (MDI)
PlaceboExperimentalParticipants will self-administer blinded placebo each morning (once daily) as one inhalation from the double-blind DPI over a treatment period of 12 weeks. Participants will receive open labeled ICS/LABA medication through out duration of the treatment period as background treatment
Receives: Drug: Placebo DPI; Drug: ICS/LABA medication; Drug: Albuterol/salbutamol Metered Dose Inhaler (MDI)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85

    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 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84 (Week 12). Trough FEV1 was measured using spirometry. BL FEV1 is the mean of the two assessments made 30 and 5 minutes (min) pre-dose on Day 1.Change from BL was calculated as the trough FEV1 value on Day 85 minus the BL value. Analysis was performed using mixed model repeated measures with covariates of treatment, BL FEV1 (mean of the values measured at 30 min and 5 min pre-dose on Day 1), type of ICS/LABA, smoking status, Day, Day by BL interaction and Day by treatment interaction, where Day is nominal.

    Measured: Baseline (BL) and Day 85

Secondary outcomes (1)

  1. Change From Baseline in Weighted Mean 0-6 Hour FEV1 Obtained Post-dose on Day 84

    FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean FEV1 was derived by calculating the area under the curve, and then dividing the value by the relevant time interval. The weighted mean was calculated by performing six-hour serial spirometry from the pre-dose FEV1 and post-dose FEV1 measurements at 15 minutes, 30 minutes, 1 hour, 3 hours and 6 hours. Baseline FEV1 is the mean of the two assessments made 30 and 5 min pre-dose on Treatment Day 1. Change from Baseline was calculated as weighted mean value on Day 84 minus the Baseline value. Analysis was performed using mixed model repeated measures with covariates of treatment, baseline FEV1 (mean of the values measured at 30 min and 5 min pre-dose on Day 1), type of ICS/LABA , smoking status, Day, Day by baseline interaction and Day by treatment interaction, where Day is nominal.

    Measured: Baseline and Day 84

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2014 (estimated)
  2. Study start30 Sep 2014
  3. Primary completion24 Mar 2015
  4. Study completion24 Mar 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
236 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02257372
Sponsor's protocol ID
201314
Status last verified
Jul 2017
First submitted
2 Oct 2014
Last updated
17 Aug 2017
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • Sousa AR, Riley JH, Church A, Zhu CQ, Punekar YS, Fahy WA. The effect of umeclidinium added to inhaled corticosteroid/long-acting beta2-agonist in patients with symptomatic COPD: a randomised, double-blind, parallel-group study. NPJ Prim Care Respir Med. 2016 Jun 23;26:16031. doi: 10.1038/npjpcrm.2016.31.

    PubMed 27334739

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing UMEC DPI, ICS/LABA medication and Albuterol/salbutamol Metered Dose Inhaler (MDI) in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 28 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in Germany, Greece, Netherlands, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85 (time frame: Baseline (BL) and Day 85). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02257372, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2017.

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