Pulmonary Disease, Chronic ObstructivePhase 3NCT02257385
Comparative Study of Umeclidinium/Vilanterol (UMEC/VI) in a Fixed Dose Combination With Indacaterol Plus Tiotropium
A Phase 3 study testing UMEC/VI, Tiotropium and Indacaterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 84 sites in 12 countries.
Trial summary
This is a Phase IIIb multicentre, randomised, blinded, triple dummy, parallel group study to evaluate the efficacy and safety of UMEC/VI inhalation powder (62.5/25 microgram [mcg] Once daily [QD]) when administered via ELLIPTA® Dry Powder Inhaler (DPI) compared to indacaterol plus tiotropium (150 mcg/18 mcg… 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/VI, Tiotropium and Indacaterol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 967 participants
- Where
- 84 sitesin 12 countries
- Study dates
- 15 Oct 2014to 4 May 2015
- Phase
- Phase 3
- 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.
- Participants 40 years of age or older at Visit 1.
- Gender: Male or female participants. 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. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.
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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 a pre and post-albuterol/salbutamol FEV1 of <=70% predicted normal value at Visit 1, calculated using Quanjer reference equations.
- Dyspnoea: A score of >= 2 on the Modified Medical Research Council Dyspnoea Scale (mMRC) at Visit 1.
- QT interval corrected (QTc) Criteria: QTc <450 milliseconds (msec) or QTc <480 msec for patients with bundle branch block The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or manual overread. For subject eligibility and withdrawal, QTcF will be used. For purposes of data analysis, QTcF will be used as primary. The QTc should be based on single or averaged QTc values of triplicate Electrocardiogram (ECGs) obtained over a brief recording period.
- French participants: 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.
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. Allergy rhinitis is not exclusionary.
- Other Diseases/Abnormalities: Participants with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for <5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
- Contraindications: A history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician, contraindicates study participation or use of an inhaled anticholinergic or beta 2 agonist.
- Hospitalisation: Hospitalisation for COPD or pneumonia within 12 weeks prior to Visit 1.
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- Lung Resection: Participants with lung volume reduction surgery within the 12 months prior to Screening (Visit 1).
- 12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1. Specific ECG findings that preclude subject eligibility will be listed in protocol The study investigator will determine the medical significance of any ECG abnormalities not listed.
- Screening labs: Significantly abnormal finding from clinical chemistry or haematology tests at Visit 1 as determined by the study investigator.
- 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); Oral or parenteral corticosteroids (6 weeks); Antibiotics (for lower respiratory tract infection) (6 weeks); Cytochrome P450 3A4 strong inhibitors ( 6 weeks); Long Acting Beta-Agonist (LABA)/ inhaled corticosteroids (ICS) combination products (e.g. fluticasone/salmeterol, mometasone, furoate/formoterol fumarate, budesonide/formoterol, fumarate), If LABA/ICS therapy is discontinued completely (30 days); If discontinuing LABA therapy and switching to ICS monotherapy (48 hours for salmeterol or formoterol, 14 days for Olodaterol, Indacaterol or, Vilanterol); Use of ICS at a dose >1000 mcg/day of fluticasone propionate or equivalent (30 days); Initiation or discontinuation of ICS use (30 days); Inhaled long acting beta2-agonists (LABA): Salmeterol, Formoterol (48 hours), Olodaterol, Indacaterol and Vilanterol (14 days); Long acting muscarinic antagonists (LAMA) (Tiotropium, Aclidinium, Glycopyrronium, Umeclidinium) (7 days); LABA/LAMA combination products (Whichever mono component has the longest washout); Roflumilast (14 days); Oral beta-agonists- Long-acting (48 hours), Short-acting(12 hours); Theophyllines (48 hours); Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton) (48 hours); Inhaled sodium cromoglycate or nedocromil sodium (24 hours); Inhaled short acting beta2-agonists (4 hours); Inhaled short-acting anticholinergic (short acting muscarinic antagonist [SAMA]) products eg ipratropium (4 hours); Inhaled short-acting anticholinergic/short-acting beta2-agonist combination products (SAMA/Short Acting beta2-agonists [SABA]) (4 hours); Any other investigational medication (30 days or within 5 drug half-lives)
- Oxygen: Use of Long Term Oxygen Therapy (LTOT).This is defined as oxygen therapy prescribed for greater than 12 hours per 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 12 weeks prior to Visit 1. Participants 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.
- Participants who are pre-screen or screen failures cannot be re-screened.
Trial locations and contacts
84 sites in 12 countries.
84 sites in 12 countries
Russia16 sites
GSK Investigational Site
Arkhangelsk, 153000
GSK Investigational Site
Irkutsk, 664079
GSK Investigational Site
Kazan', 420015
GSK Investigational Site
Moscow, 115 478
GSK Investigational Site
Moscow, 125284
GSK Investigational Site
Omsk, 644112
GSK Investigational Site
Orenburg, 460040
GSK Investigational Site
Perm, 614068
GSK Investigational Site
Saint Petersburg, 194356
GSK Investigational Site
Saint Petersburg, 198216
GSK Investigational Site
Saint Petesburg, 195030
GSK Investigational Site
Stavropol, 355017
GSK Investigational Site
Tomsk, 634063
GSK Investigational Site
Ulyanovsk, 432063
GSK Investigational Site
Yekaterinburg, 620039
GSK Investigational Site
Yekaterinburg, 620149
Germany11 sites
GSK Investigational Site
Berlin, 10367
GSK Investigational Site
Berlin, 10787
GSK Investigational Site
Berlin, 12203
GSK Investigational Site
Frankfurt am Main, Hesse, 60389
GSK Investigational Site
Frankfurt am Main, Hesse, 60596
GSK Investigational Site
Hamburg, 20253
GSK Investigational Site
Hamburg, 20354
GSK Investigational Site
Hamburg, 22299
GSK Investigational Site
Magdeburg, Saxony-Anhalt, 39112
GSK Investigational Site
Rüdersdorf, Brandenburg, 15562
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, 19055
Argentina8 sites
GSK Investigational Site
Buenos Aires, C1424BSF
GSK Investigational Site
Buenos Aires, C1425BEN
GSK Investigational Site
Buenos Aires, C1426ABP
GSK Investigational Site
Mar del Plata, Buenos Aires, 7600
GSK Investigational Site
Mendoza, 5500
GSK Investigational Site
Mendoza, M5500CCG
GSK Investigational Site
San Miguel de Tucumán, Tucumán Province, 4000
GSK Investigational Site
San Miguel de Tucumán, 4000
Hungary8 sites
GSK Investigational Site
Balassagyarmat, 2660
GSK Investigational Site
Budaörs, 2040
GSK Investigational Site
Debrecen, 4032
GSK Investigational Site
Gödöllő, 2100
GSK Investigational Site
Nyíregyháza, 4400
GSK Investigational Site
Pécs, 7635
GSK Investigational Site
Szeged, 6722
GSK Investigational Site
Szikszó, 3800
Romania7 sites
GSK Investigational Site
Bucharest, 020125
GSK Investigational Site
Bucharest, 050159
GSK Investigational Site
Cluj-Napoca, 400371
GSK Investigational Site
Constanța, 900002
GSK Investigational Site
Râmnicu Vâlcea, 240564
GSK Investigational Site
Timișoara, 300310
GSK Investigational Site
Timișoara, 300465
France6 sites
GSK Investigational Site
Gières, 38610
GSK Investigational Site
Nantes, 44277
GSK Investigational Site
Perpignan, 66000
GSK Investigational Site
Reims, 51092
GSK Investigational Site
Strasbourg, 67091
GSK Investigational Site
Tarbes, 65013
Poland6 sites
GSK Investigational Site
Elblag, 82-300
GSK Investigational Site
Krakow, 31-024
GSK Investigational Site
Ostrów Wielkopolski, 63-400
GSK Investigational Site
Piekary Śląskie, 41-940
GSK Investigational Site
Słupsk, 76-200
GSK Investigational Site
Sopot, 81-741
Italy5 sites
GSK Investigational Site
Mantua, Lombardy, 46100
GSK Investigational Site
Novara, Piedmont, 28100
GSK Investigational Site
Piacenza, Emilia-Romagna, 29121
GSK Investigational Site
Pordenone, Friuli Venezia Giulia, 33170
GSK Investigational Site
Tradate (VA), Lombardy, 21049
Peru5 sites
GSK Investigational Site
Lima, Lima Province, Lima 27
GSK Investigational Site
Lima, Lima 14
GSK Investigational Site
Lima, Lima 18
GSK Investigational Site
Lima, Lima 1
GSK Investigational Site
Lima, Lima 32
Slovakia5 sites
GSK Investigational Site
Bojnice, 972 01
GSK Investigational Site
Humenné, 066 01
GSK Investigational Site
Poprad, 058 01
GSK Investigational Site
Spišská Nová Ves, 052 01
GSK Investigational Site
Vráble, 952 01
Chile4 sites
GSK Investigational Site
Puente Alto - Santiago, Región Metro de Santiago, 8207257
GSK Investigational Site
Santiago, Región Metro de Santiago, 7500692
GSK Investigational Site
Santiago, Región Metro de Santiago, 7510186
GSK Investigational Site
Santiago, 7500698
Estonia3 sites
GSK Investigational Site
Haapsalu, 90502
GSK Investigational Site
Tallinn, 10117
GSK Investigational Site
Tallinn, 10138
About this study
Official title: Study DB2116961, A Multicentre, Randomised, Blinded, Parallel Group Study to Compare UMEC/VI (Umeclidinium/Vilanterol) in a Fixed Dose Combination With Indacaterol Plus Tiotropium in Symptomatic Subjects With Moderate to Very Severe COPD
This is a Phase IIIb multicentre, randomised, blinded, triple dummy, parallel group study to evaluate the efficacy and safety of UMEC/VI inhalation powder (62.5/25 microgram [mcg] Once daily [QD]) when administered via ELLIPTA® Dry Powder Inhaler (DPI) compared to indacaterol plus tiotropium (150 mcg/18 mcg respectively QD) administered via individual inhalers over a treatment period of 12 weeks in participants with moderate to very severe Chronic Obstructive Pulmonary Disease (COPD). The purpose of this study is to demonstrate that UMEC/VI (delivered via ELLIPTA DPI), when used in symptomatic moderate to very severe COPD participants, is non-inferior to the combination of indacaterol (delivered via BREEZHALER® inhaler) plus tiotropium (delivered via HANDIHALER® inhaler) on measures of trough forced expiratory volume in one second (FEV1) after 12 weeks of treatment. Participants who met the eligibility criteria at screening (Visit 1) will complete a 5 to 7 day run in period prior to randomisation at Visit 2. Clinic visits will follow at day 2, week 2, week 4, week 8 and week 12 of treatment, plus week 12 + 1 day (Visits 3 to 8). The total duration of study participation will be approximately 14 weeks. ELLIPTA is a registered trademark of the GSK group of companies. HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH \& Co. KG. BREEZHALER is a registered trademark of Novartis AG.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- UMEC/VI, UMEC/VI matching placebo, Tiotropium, Tiotropium matching placebo, Indacaterol
- Keywords
- indacaterol, efficacy, FEV1, ELLIPTA, non inferiority, vilanterol, COPD, safety, tiotropium, umeclidinium bromide, GSK573719
- 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/VIDrug
ELLIPTA DPI will be supplied with 30 doses (2 strips with 30 blisters per strip) where first strip contains Umeclidinium bromide (unit dose strengths 62.5 mcg per blister) blended with lactose monohydrate and magnesium stearate 0.6% weight/weight (w/w) of total drug product and second strip contains Vilanterol (unit dose strengths 25 mcg per blister) blended with lactose monohydrate and magnesium stearate 1.0% w/w of total drug product
UMEC/VI matching placeboDrug
ELLIPTA DPI will be supplied with 30 doses (2 strips with 30 blisters per strip) where first strip contains lactose monohydrate and magnesium stearate 0.6% w/w of total drug product and second strip contains lactose monohydrate and magnesium stearate 1.0% w/w of total drug product
TiotropiumDrug
Tiotropium (as bromide monohydrate) inhalation capsules 18 mcg per dose will be supplied along with HANDIHALER inhalers manufactured by Boehringer Ingelheim
Tiotropium matching placeboDrug
Tiotropium matching placebo capsules manufactured by GSK, will contain lactose and will be supplied along with HANDIHALER inhalers
IndacaterolDrug
Indacaterol inhalation capsules 150 mcg per dose will be supplied by GSK along with BREEZHALER inhalers manufactured by Novartis
Indacaterol matching placeboDrug
Indacaterol matching placebo capsules manufactured by GSK, will contain lactose and will be supplied along with BREEZHALER inhalers manufactured by Novartis
Albuterol/salbutamol Metered Dose Inhaler (MDI)Drug
Albuterol/salbutamol MDI or nebules for as needed use will be issued throughout the study. Albuterol/salbutamol will be sourced from local commercial stock. If not available locally, GSK will source centrally
| Study group | Role | What they receive |
|---|---|---|
| UMEC/VI arm | Experimental | Participants will be instructed to self-administer one dose each morning of UMEC/VI Inhalation Powder 62.5/25 mcg once daily via ELLIPTA DPI, placebo once daily via HANDIHALER inhaler and placebo once daily via BREEZHALER inhaler Receives: Drug: UMEC/VI; Drug: UMEC/VI matching placebo; Drug: Albuterol/salbutamol Metered Dose Inhaler (MDI) |
| Tiotropium + Indacaterol arm | Placebo comparator | Participants will be instructed to self-administer one dose each morning of Tiotropium bromide 18 mcg once daily via HANDIHALER inhaler, Indacaterol 150 mcg once daily via BREEZHALER inhaler and placebo once daily via ELLIPTA DPI Receives: Drug: Tiotropium; Drug: Tiotropium matching placebo; Drug: Indacaterol; Drug: Indacaterol matching placebo; Drug: Albuterol/salbutamol Metered Dose Inhaler (MDI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Treatment Day 85 (Visit 8)
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in 1 second. BL was the mean of the 2 assessments made 30 and 5 minutes (min) pre-dose (PD) on Day 1. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained at 23 and 24 hours (hr) after dosing on Day 84 (at Week 12 + 1 day). Analysis was performed using mixed model repeated measures (RM) with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1), center group, day, day by BL interaction and day by trt interaction, where day was nominal.
Measured: Baseline (BL) and Day 85
Secondary outcomes (1)
Change From Baseline in Weighted Mean (WM) FEV1 Over 0-6 Hour Post-dose at Day 84
BL FEV1 was the mean of the 2 assessments made 30 and 5 min PD on Day 1. WM FEV1 derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM was calculated at Days 1 and 84 using the 0-6 hr post-dose FEV1 measurements collected on that day, which included PD FEV1 (taken 30 and 5 min prior to dosing on Day 1 and the 30 and 5 min reading prior to dosing on Day 84) and post-dose FEV1 measurements at 1, 3 and 6 hr post-dose.WM change from BL was the WM at at the visit minus the BL value. Analysis was performed using a RM model with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1) center group, day, day by BL and day by trt interaction, where day was nominal. Only par with data available at the specified TP were analyzed but all par w/o missing covariate information and with >=1 post-BL measurement were included in the analysis.
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.
- First posted6 Oct 2014 (estimated)
- Study start15 Oct 2014
- Primary completion4 May 2015
- Study completion4 May 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 967 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02257385
- Sponsor's protocol ID
- 116961
- Status last verified
- Feb 2018
- First submitted
- 2 Oct 2014
- Last updated
- 1 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- 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
Kalberg C, O'Dell D, Galkin D, Newlands A, Fahy WA. Dual Bronchodilator Therapy with Umeclidinium/Vilanterol Versus Tiotropium plus Indacaterol in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial. Drugs R D. 2016 Jun;16(2):217-27. doi: 10.1007/s40268-016-0131-2.
PubMed 27028749
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study DB2116961, A Multicentre, Randomised, Blinded, Parallel Group Study to Compare UMEC/VI (Umeclidinium/Vilanterol) in a Fixed Dose Combination With Indacaterol Plus Tiotropium in Symptomatic Subjects With Moderate to Very Severe COPD
- ClinicalTrials.gov ID
- NCT02257385
- Acronym / sponsor ID
- 116961
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- indacaterol, efficacy, FEV1, ELLIPTA, non inferiority, vilanterol, COPD, safety
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 967 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 15 Oct 2014 (actual)
- Primary completion
- 4 May 2015 (actual)
- Study completion
- 4 May 2015 (actual)
- First posted
- 6 Oct 2014 (estimated)
- Results
- Posted 3 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase IIIb multicentre, randomised, blinded, triple dummy, parallel group study to evaluate the efficacy and safety of UMEC/VI inhalation powder (62.5/25 microgram [mcg] Once daily [QD]) when administered via ELLIPTA® Dry Powder Inhaler (DPI) compared to indacaterol plus tiotropium (150 mcg/18 mcg respectively QD) administered via individual inhalers over a treatment period of 12 weeks in participants with moderate to very severe Chronic Obstructive Pulmonary Disease (COPD). The purpose of this study is to demonstrate that UMEC/VI (delivered via ELLIPTA DPI), when used in symptomatic moderate to very severe COPD participants, is non-inferior to the combination of indacaterol (delivered via BREEZHALER® inhaler) plus tiotropium (delivered via HANDIHALER® inhaler) on measures of trough forced expiratory volume in one second (FEV1) after 12 weeks of treatment. Participants who met the eligibility criteria at screening (Visit 1) will complete a 5 to 7 day run in period prior to randomisation at Visit 2. Clinic visits will follow at day 2, week 2, week 4, week 8 and week 12 of treatment, plus week 12 + 1 day (Visits 3 to 8). The total duration of study participation will be approximately 14 weeks. ELLIPTA is a registered trademark of the GSK group of companies. HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH \& Co. KG. BREEZHALER is a registered trademark of Novartis AG.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| UMEC/VI arm | Experimental | Drug: UMEC/VI, Drug: UMEC/VI matching placebo, Drug: Albuterol/salbutamol Metered Dose Inhaler (MDI)Participants will be instructed to self-administer one dose each morning of UMEC/VI Inhalation Powder 62.5/25 mcg once daily via ELLIPTA DPI, placebo once daily via HANDIHALER inhaler and placebo once daily via BREEZHALER inhaler |
| Tiotropium + Indacaterol arm | Placebo comparator | Drug: Tiotropium, Drug: Tiotropium matching placebo, Drug: Indacaterol, Drug: Indacaterol matching placebo, Drug: Albuterol/salbutamol Metered Dose Inhaler (MDI)Participants will be instructed to self-administer one dose each morning of Tiotropium bromide 18 mcg once daily via HANDIHALER inhaler, Indacaterol 150 mcg once daily via BREEZHALER inhaler and placebo once daily via ELLIPTA DPI |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Type of subject: Outpatient
- Informed Consent: A signed and dated written informed consent prior to study participation.
- Participants 40 years of age or older at Visit 1.
- Gender: Male or female participants. 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.
Key exclusion criteria (18 listed)
- 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. Allergy rhinitis is not exclusionary.
- Other Diseases/Abnormalities: Participants with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for <5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
- Contraindications: A history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician, contraindicates study participation or use of an inhaled anticholinergic or beta 2 agonist.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UMEC/VIELLIPTA DPI will be supplied with 30 doses (2 strips with 30 blisters per strip) where first strip contains Umeclidinium bromide (unit dose strengths 62.5 mcg per blister) blended with lactose monohydrate and magnesium stearate 0.6% weight/weight (w/w) of total drug product and second strip contains Vilanterol (unit dose strengths 25 mcg per blister) blended with lactose monohydrate and magnesium stearate 1.0% w/w of total drug product | Drug | UMEC/VI arm |
| UMEC/VI matching placeboELLIPTA DPI will be supplied with 30 doses (2 strips with 30 blisters per strip) where first strip contains lactose monohydrate and magnesium stearate 0.6% w/w of total drug product and second strip contains lactose monohydrate and magnesium stearate 1.0% w/w of total drug product | Drug | UMEC/VI arm |
| TiotropiumTiotropium (as bromide monohydrate) inhalation capsules 18 mcg per dose will be supplied along with HANDIHALER inhalers manufactured by Boehringer Ingelheim | Drug | Tiotropium + Indacaterol arm |
| Tiotropium matching placeboTiotropium matching placebo capsules manufactured by GSK, will contain lactose and will be supplied along with HANDIHALER inhalers | Drug | Tiotropium + Indacaterol arm |
| IndacaterolIndacaterol inhalation capsules 150 mcg per dose will be supplied by GSK along with BREEZHALER inhalers manufactured by Novartis | Drug | Tiotropium + Indacaterol arm |
| Indacaterol matching placeboIndacaterol matching placebo capsules manufactured by GSK, will contain lactose and will be supplied along with BREEZHALER inhalers manufactured by Novartis | Drug | Tiotropium + Indacaterol arm |
| Albuterol/salbutamol Metered Dose Inhaler (MDI)Albuterol/salbutamol MDI or nebules for as needed use will be issued throughout the study. Albuterol/salbutamol will be sourced from local commercial stock. If not available locally, GSK will source centrally | Drug | Tiotropium + Indacaterol arm, UMEC/VI arm |
Primary outcome
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Treatment Day 85 (Visit 8)
Time frame: Baseline (BL) and Day 85
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in 1 second. BL was the mean of the 2 assessments made 30 and 5 minutes (min) pre-dose (PD) on Day 1. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained at 23 and 24 hours (hr) after dosing on Day 84 (at Week 12 + 1 day). Analysis was performed using mixed model repeated measures (RM) with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1), center group, day, day by BL interaction and day by trt interaction, where day was nominal.
1 secondary outcome
Change From Baseline in Weighted Mean (WM) FEV1 Over 0-6 Hour Post-dose at Day 84
Time frame: Baseline and Day 84
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27028749Kalberg C, O'Dell D, Galkin D, Newlands A, Fahy WA. Dual Bronchodilator Therapy with Umeclidinium/Vilanterol Versus Tiotropium plus Indacaterol in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial. Drugs R D. 2016 Jun;16(2):217-27. doi: 10.1007/s40268-016-0131-2.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
84 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing UMEC/VI, Tiotropium and Indacaterol in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 84 sites in 12 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 10 inclusion and 18 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 1 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 84 sites in Russia, Germany, Argentina, Hungary, Romania and 7 more countries. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 3 Mar 2016). 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 Treatment Day 85 (Visit 8) (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 NCT02257385, 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 1 Mar 2018.