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

NCT02799784 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 204990
• Study Type: interventional
• Target: 236
• Locations: 4 countries
• Sites: 35

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

tiotropium; COPD; olodaterol; Umeclidinium bromide; efficacy; vilanterol

Outcome Measures

Primary Outcomes (1)

• Trough Forced Expiratory Volume in One Second (FEV1) at 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.

  Week 8

Study Arms (2)

Sequence 1: UMEC/VI 62.5/ 25 mcg

EXPERIMENTAL

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; Drug: Albuterol/salbutamol

Sequence 2: TIO/OLO 5/5 mcg

EXPERIMENTAL

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; Drug: Albuterol/salbutamol

Interventions

UMEC/VI 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

Sequence 1: UMEC/VI 62.5/ 25 mcg

TIO/OLO 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)

Sequence 2: TIO/OLO 5/5 mcg

Albuterol/salbutamol 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 1: UMEC/VI 62.5/ 25 mcg; Sequence 2: TIO/OLO 5/5 mcg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (35)

GSK Investigational Site

Clearwater, Florida, 33765, United States

Location

GSK Investigational Site

Orlando, Florida, 32825, United States

Location

GSK Investigational Site

St Louis, Missouri, 63141, United States

Location

GSK Investigational Site

Medford, Oregon, 97504, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29406-7108, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29615, United States

Location

GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

GSK Investigational Site

Richmond, Virginia, 23229, United States

Location

GSK Investigational Site

Morgantown, West Virginia, 26505, United States

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60389, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Neu-Isenburg, Hesse, 63263, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30159, Germany

Location

GSK Investigational Site

Dresden, Saxony, 01069, Germany

Location

GSK Investigational Site

Leipzig, Saxony, 04357, Germany

Location

GSK Investigational Site

Jerichow, Saxony-Anhalt, 39319, Germany

Location

GSK Investigational Site

Magdeburg, 39120, Germany

Location

GSK Investigational Site

Marbella - Málaga, Andalusia, 29603, Spain

Location

GSK Investigational Site

Alicante, 03004, Spain

Location

GSK Investigational Site

Girona, 17005, Spain

Location

GSK Investigational Site

Loja/ Granada, 18300, Spain

Location

GSK Investigational Site

Mérida (Badajoz), 06800, Spain

Location

GSK Investigational Site

Ponferrada (León), 24411, Spain

Location

GSK Investigational Site

Valladolid, 47012, Spain

Location

GSK Investigational Site

Cheadle, Cheshire, SK8 5LL, United Kingdom

Location

GSK Investigational Site

Chesterfield, Derbyshire, S40 4AA, United Kingdom

Location

GSK Investigational Site

Romford, Essex, RM1 3PJ, United Kingdom

Location

GSK Investigational Site

Manchester, Greater Manchester, M22 4DH, United Kingdom

Location

GSK Investigational Site

Salford, Greater Manchester, M6 7HL, United Kingdom

Location

GSK Investigational Site

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

GSK Investigational Site

Addlestone, Surrey, KT15 2BH, United Kingdom

Location

GSK Investigational Site

Bristol, BS37 4AX, United Kingdom

Location

GSK Investigational Site

Chippenham, SN15 2SB, United Kingdom

Location

GSK Investigational Site

Sidcup, Kent, DA14 6LT, United Kingdom

Location

GSK Investigational Site

Swinton, M27 8HP, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 32026389 DERIVED

• 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.

  PMID: 29094315 DERIVED

Related Links

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

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Albuterol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2016
• First Posted: June 15, 2016
• Study Start: July 14, 2016
• Primary Completion: April 27, 2017
• Study Completion: April 27, 2017
• Last Updated: July 2, 2018
• Results First Posted: July 2, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

ES (7); US (9); DE (8); GB (11)