An Efficacy Study of Umeclidinium/Vilanterol With Tiotropium/Olodaterol in COPD Patients

NCT ID: NCT02799784

Last Updated: 2018-07-02

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

236 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-14

Study Completion Date

2017-04-27

Brief Summary

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The primary objective of this study is to assess the effect of umeclidinium/vilanterol (UMEC/VI) versus tiotropium/olodaterol (TIO/OLO) in subjects with moderated COPD.

This is a multicentre, randomized, open label, 2 period crossover complete block design study.

Eligible subjects, who complete a 2-week run-in period, will be randomized to receive a sequence consisting of UMEC/VI inhalation powder (62.5/25 microgram \[mcg\] once-daily \[QD\]) administered as 1 inhalation via the ELLIPTA® Inhaler and TIO/OLO 5/5 mcg inhalation spray administered as 2 inhalations via the RESPIMAT® inhaler, for 8 weeks each. This will be followed by a 3-week washout period and one-week follow-up period. The total duration of subject participation in the study will be approximately 22 weeks.

ELLIPTA is a registered trademark of the GlaxoSmithKline group of companies. RESPIMAT is a registered trademark of Boehringer Ingelheim.

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Detailed Description

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Conditions

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Pulmonary Disease, Chronic Obstructive

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sequence 1: UMEC/VI 62.5/ 25 mcg

Subjects will receive UMEC/VI 62.5/25 mcg (as one inhalation) administered QD via the ELLIPTA Inhaler for 8 weeks followed by a washout period of 3 weeks

Group Type EXPERIMENTAL

UMEC/VI

Intervention Type DRUG

ELLIPTA dry powder inhaler (DPI) will contain a total of 30 doses. Each DPI will be comprised of two double-foil, laminate blister strips. Each blister of one strip will consist of 62.5 mcg of UMEC blended with lactose and magnesium stearate while each blister of other strip will consist of 25 mcg of VI blended with lactose and magnesium stearate. Each actuation of the DPI will deliver the contents of one blister from each strip simultaneously

Albuterol/salbutamol

Intervention Type DRUG

Albuterol/salbutamol will be supplied as an inhalation spray via metered dose inhaler and will be issued for reversibility testing at Visit 1. Albuterol/salbutamol will be permitted throughout the study for use as-needed

Sequence 2: TIO/OLO 5/5 mcg

Subjects will receive TIO/OLO 5/5 mcg (as 2 inhalations of 2.5/2.5 mcg per inhalation) administered QD via the RESPIMAT inhaler for 8 weeks followed by a washout period of 3 weeks

Group Type EXPERIMENTAL

TIO/OLO

Intervention Type DRUG

TIO/OLO inhalation spray will be supplied as an inhalation spray delivered using a RESPIMAT inhaler. Each actuation from the RESPIMAT inhaler delivers 3.124 mcg tiotropium bromide monohydrate (equivalent to 2.5 mcg tiotropium) and 2.736 mcg olodaterol hydrochloride (equivalent to 2.5 mcg olodaterol)

Albuterol/salbutamol

Intervention Type DRUG

Albuterol/salbutamol will be supplied as an inhalation spray via metered dose inhaler and will be issued for reversibility testing at Visit 1. Albuterol/salbutamol will be permitted throughout the study for use as-needed

Interventions

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UMEC/VI

ELLIPTA dry powder inhaler (DPI) will contain a total of 30 doses. Each DPI will be comprised of two double-foil, laminate blister strips. Each blister of one strip will consist of 62.5 mcg of UMEC blended with lactose and magnesium stearate while each blister of other strip will consist of 25 mcg of VI blended with lactose and magnesium stearate. Each actuation of the DPI will deliver the contents of one blister from each strip simultaneously

Intervention Type DRUG

TIO/OLO

TIO/OLO inhalation spray will be supplied as an inhalation spray delivered using a RESPIMAT inhaler. Each actuation from the RESPIMAT inhaler delivers 3.124 mcg tiotropium bromide monohydrate (equivalent to 2.5 mcg tiotropium) and 2.736 mcg olodaterol hydrochloride (equivalent to 2.5 mcg olodaterol)

Intervention Type DRUG

Albuterol/salbutamol

Albuterol/salbutamol will be supplied as an inhalation spray via metered dose inhaler and will be issued for reversibility testing at Visit 1. Albuterol/salbutamol will be permitted throughout the study for use as-needed

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Outpatients of either sex, 40 years of age or older at Visit 1, and with a diagnosis of chronic obstructive pulmonary disease (COPD) defined by the American Thoracic Society/European Respiratory Society (ERS)
* A signed and dated written informed consent prior to study participation
* A female is eligible to enter and participate in the study if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin \[hCG\] test); not lactating; and of non-reproductive potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile), which is defined as pre-menopausal females with one of the following: documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral or tubal occlusion ; hysterectomy; documented bilateral oophorectomy.

Postmenopausal is defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment OR

* A female of reproductive potential, has a negative pregnancy test at screening, and agrees to one of the methods below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from methods used consistently and correctly (i.e., in accordance with the local approved product label and per study investigator discretion and the instructions of the physician from 30 days prior to the first dose of study medication and until to follow-up contact):

GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP (this list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis).

* Contraceptive subdermal implant that meets the standard operating procedure (SOP) effectiveness criteria including a \<1% rate of failure per year, as stated in the product label
* Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a \<1% rate of failure per year, as stated in the product label
* Oral Contraceptive, either combined or progestogen alone
* Injectable progestogen
* Contraceptive vaginal ring
* Percutaneous contraceptive patches
* Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject.

These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception

* 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. Pipe and/or cigar use cannot be used to calculate pack-year history.
* A pre and post-albuterol/salbutamol forced expiratory volume in one second (FEV1)/Forced Vital Capacity ratio of \<0.70 and a post-albuterol/salbutamol FEV1 of \<=70% to \>=50 % of predicted normal values at Visit 1. Predicted values will be based upon the ERS' Global Lung Function Initiative
* A score of \>=2 on the Modified Medical Research Council Dyspnea Scale at Visit 1

Exclusion Criteria

* Women who are pregnant or lactating or are planning on becoming pregnant during the study
* A current diagnosis of asthma
* Subjects with alpha-1 antitrypsin deficiency as the underlying cause of COPD
* Subjects with active tuberculosis are excluded. Subjects with other respiratory disorders (e.g. clinically significant: bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases) are excluded if these conditions are the primary cause of their respiratory symptoms.
* 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 other condition (e.g. neurological condition) that is likely to affect respiratory function should not be included in the study
* Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment
* Investigational Product 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

* Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, sympathomimetic, lactose/milk protein or magnesium stearate
* Subjects with medical conditions such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction should be excluded unless, in the opinion of the study physician, the benefit outweighs the risk
* Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1. Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 14 days prior to Screening (V1) and at least 30 days following the last dose of oral/systemic corticosteroids (if applicable).
* Other respiratory tract infections that have not resolved at least 7 days prior to Screening (V1).
* Subjects with lung volume reduction surgery (including procedures such as endobronchial valves) within the 12 months prior to Screening (V1).
* The Investigator will determine the clinical significance of each abnormal electrocardiogram finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial
* Unable to withhold albuterol/salbutamol for the 4-hour (h) period required prior to spirometry testing at each study visit
* Use of the pre-defined medications according to the pre-defined defined time intervals prior to Screening (Visit 1)
* Use of long-term oxygen therapy described as resting oxygen therapy \>3 liter (L)/minute (min) at screening. (Oxygen use \<=3 L/min flow is not exclusionary, and patients may adjust oxygen levels as needed during the study.)
* Regular use (prescribed for daily/ regular use, not for as-needed use) of short-acting bronchodilators (e.g. albuterol/salbutamol).
* Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening (Visit 1). Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded
* A known or suspected history of alcohol or drug abuse within 2 years prior to Screening (Visit 1) that in the opinion of the investigator would prevent the subject from completing the study procedures
* 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
* In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete a questionnaire.
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

Clearwater, Florida, United States

Site Status

GSK Investigational Site

Orlando, Florida, United States

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GSK Investigational Site

St Louis, Missouri, United States

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GSK Investigational Site

Medford, Oregon, United States

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Charleston, South Carolina, United States

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Greenville, South Carolina, United States

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Spartanburg, South Carolina, United States

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GSK Investigational Site

Richmond, Virginia, United States

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GSK Investigational Site

Morgantown, West Virginia, United States

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Frankfurt am Main, Hesse, Germany

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Frankfurt am Main, Hesse, Germany

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Neu-Isenburg, Hesse, Germany

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Hanover, Lower Saxony, Germany

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Dresden, Saxony, Germany

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Leipzig, Saxony, Germany

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Jerichow, Saxony-Anhalt, Germany

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Magdeburg, , Germany

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Marbella - Málaga, Andalusia, Spain

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Alicante, , Spain

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Girona, , Spain

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Loja/ Granada, , Spain

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Mérida (Badajoz), , Spain

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Ponferrada (León), , Spain

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Valladolid, , Spain

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Cheadle, Cheshire, United Kingdom

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Chesterfield, Derbyshire, United Kingdom

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Romford, Essex, United Kingdom

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Manchester, Greater Manchester, United Kingdom

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Salford, Greater Manchester, United Kingdom

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Northwood, Middlesex, United Kingdom

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Addlestone, Surrey, United Kingdom

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Bristol, , United Kingdom

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Chippenham, , United Kingdom

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Sidcup, Kent, , United Kingdom

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GSK Investigational Site

Swinton, , United Kingdom

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Countries

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United States Germany Spain United Kingdom

References

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Alcazar Navarrete B, Boucot I, Naya I, Tombs L, Lipson DA, Compton C, Sousa AR, Feldman G. Umeclidinium/Vilanterol Versus Tiotropium/Olodaterol in Maintenance-Naive Patients with Moderate Symptomatic Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis. Pulm Ther. 2018 Dec;4(2):171-183. doi: 10.1007/s41030-018-0057-7. Epub 2018 Jun 20.

Reference Type DERIVED
PMID: 32026389 (View on PubMed)

Feldman GJ, Sousa AR, Lipson DA, Tombs L, Barnes N, Riley JH, Patel S, Naya I, Compton C, Alcazar Navarrete B. Comparative Efficacy of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol Therapy in Symptomatic Chronic Obstructive Pulmonary Disease: A Randomized Study. Adv Ther. 2017 Nov;34(11):2518-2533. doi: 10.1007/s12325-017-0626-4. Epub 2017 Nov 1.

Reference Type DERIVED
PMID: 29094315 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://clinicalstudydatarequest.com

IPD for this study will be made available via the Clinical Study Data Request site.

Other Identifiers

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204990

Identifier Type: -

Identifier Source: org_study_id

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