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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02799784
Recruitment Status : Completed
First Posted : June 15, 2016
Results First Posted : July 2, 2018
Last Update Posted : July 2, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Pulmonary Disease, Chronic Obstructive Drug: UMEC/VI Drug: TIO/OLO Drug: Albuterol/salbutamol Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 236 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, 8-Week Cross-Over Study to Compare Umeclidinium/Vilanterol With Tiotropium/Olodaterol Once-Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Actual Study Start Date : July 14, 2016
Actual Primary Completion Date : April 27, 2017
Actual Study Completion Date : April 27, 2017


Arm Intervention/treatment
Experimental: 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
Drug: 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

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

Experimental: 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
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)

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




Primary Outcome Measures :
  1. Trough Forced Expiratory Volume in One Second (FEV1) at Week 8 [ Time Frame: Week 8 ]
    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 was defined as 23 and 24 hour post-dose FEV1 measurements. All par. in the Intent To Treat (ITT) Population who were not identified as full protocol deviators were included in Per-Protocol (PP) Population. ITT Population, comprised of all randomized subjects, who received at least one dose of study medication.



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02799784


Locations
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United States, Florida
GSK Investigational Site
Clearwater, Florida, United States, 33765
GSK Investigational Site
Orlando, Florida, United States, 32825
United States, Missouri
GSK Investigational Site
Saint Louis, Missouri, United States, 63141
United States, Oregon
GSK Investigational Site
Medford, Oregon, United States, 97504
United States, South Carolina
GSK Investigational Site
Charleston, South Carolina, United States, 29406-7108
GSK Investigational Site
Greenville, South Carolina, United States, 29615
GSK Investigational Site
Spartanburg, South Carolina, United States, 29303
United States, Virginia
GSK Investigational Site
Richmond, Virginia, United States, 23229
United States, West Virginia
GSK Investigational Site
Morgantown, West Virginia, United States, 26505
Germany
GSK Investigational Site
Frankfurt, Hessen, Germany, 60389
GSK Investigational Site
Frankfurt, Hessen, Germany, 60596
GSK Investigational Site
Neu-Isenburg, Hessen, Germany, 63263
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30159
GSK Investigational Site
Jerichow, Sachsen-Anhalt, Germany, 39319
GSK Investigational Site
Dresden, Sachsen, Germany, 01069
GSK Investigational Site
Leipzig, Sachsen, Germany, 04357
GSK Investigational Site
Magdeburg, Germany, 39120
Spain
GSK Investigational Site
Marbella - Málaga, Andalucia, Spain, 29603
GSK Investigational Site
Alicante, Spain, 03004
GSK Investigational Site
Gerona, Spain, 17005
GSK Investigational Site
Loja/ Granada, Spain, 18300
GSK Investigational Site
Mérida (Badajoz), Spain, 06800
GSK Investigational Site
Ponferrada (León), Spain, 24411
GSK Investigational Site
Valladolid, Spain, 47012
United Kingdom
GSK Investigational Site
Cheadle, Cheshire, United Kingdom, SK8 5LL
GSK Investigational Site
Chesterfield, Derbyshire, United Kingdom, S40 4AA
GSK Investigational Site
Romford, Essex, United Kingdom, RM1 3PJ
GSK Investigational Site
Manchester, Greater Manchester, United Kingdom, M22 4DH
GSK Investigational Site
Salford, Greater Manchester, United Kingdom, M6 7HL
GSK Investigational Site
Northwood, Middlesex, United Kingdom, HA6 2RN
GSK Investigational Site
Addlestone, Surrey, United Kingdom, KT15 2BH
GSK Investigational Site
Bristol, United Kingdom, BS37 4AX
GSK Investigational Site
Chippenham, United Kingdom, SN15 2SB
GSK Investigational Site
Sidcup, Kent, United Kingdom, DA14 6LT
GSK Investigational Site
Swinton, United Kingdom, M27 8HP
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] March 29, 2016
Statistical Analysis Plan  [PDF] May 26, 2017

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02799784    
Other Study ID Numbers: 204990
First Posted: June 15, 2016    Key Record Dates
Results First Posted: July 2, 2018
Last Update Posted: July 2, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: https://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
tiotropium
COPD
olodaterol
Umeclidinium bromide
efficacy
vilanterol
Additional relevant MeSH terms:
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Lung Diseases
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Lung Diseases, Obstructive
Albuterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action