Evaluation of Umeclidinium Bromide in Combination With Fluticasone Furoate in COPD Subjects With an Asthmatic Component

NCT02164539 | Completed Phase 2 Results

• 1 other identifier: 200699
• Study Type: interventional
• Target: 338
• Locations: 7 countries
• Sites: 67

Brief Summary

The purpose of this study is to evaluate the dose-response of 4 doses of umeclidinium bromide in combination with fluticasone furoate compared with fluticasone furoate monotherapy in chronic obstructive pulmonary disease participants with an asthmatic component. The fluticasone furoate/umeclidinium bromide treatments will also be compared to the once-daily inhaled corticosteroid/long-acting beta agonist combination fluticasone furoate/vilanterol.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

GSK573719; asthma; UMEC; FF; GSK2829332; persistent obstruction; GW685698; Fluticasone Furoate; COPD; umeclidinium bromide

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Clinic Trough Forced Expiratory Volume in One Second (FEV1) at the End of Treatment Phase A (Visit 6/Day 29)

  FEV1 is defined as forced expiratory volume in one second and measured in the morning at Visits 1 through 8 between 6:00 and 11:00 electronically by spirometry. Change from Baseline in trough FEV1 is defined as the difference in the value obtained at Visit 6 (24 hours post-dose on Visit 5) and the last acceptable/borderline acceptable value obtained prior to randomization (from Visit 2 pre-bronchodilator or Visit 3 pre-dose). Trough FEV1 is defined as the acceptable/borderline acceptable FEV1 value obtained at Visit 6, approximately 24 hours after morning dosing on Visit 5. ITT population is comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period. All comparisons for statistical purposes are with the FF 100 µg arm.

  Baseline and Day 29

Secondary Outcomes (5)

• Mean Change From Baseline in Rescue Medication Use at the End of Treatment Phase A

  Baseline and End of Treatment Phase A (The end of Treatment Phase A was defined as the last 7 days of Treatment Phase A, including the AM assessments on the date of Visit 6)

• Mean Change From Baseline in E-RS Total Scores at the End of Treatment Phase A

  Baseline and End of Treatment Phase A (The end of Treatment Phase A was defined as the last 7 days of Treatment Phase A, including the AM assessments on the date of Visit 6)

• Change From Baseline in Daily Morning (AM) PEF (Pre-dose and Pre-rescue Bronchodilator) Measured at Home and Averaged Over the Last 21 Days of Treatment Phase A

  Baseline and from Day 8 through Day 29

• Change From Trough in Clinic Forced Expiratory Volume (FEV1) at 3 Hours Post-study Treatment at Visit 5/Day 28

  Baseline and Day 28

• Change in Clinic FEV1 Following 2 Puffs of Albuterol/Salbutamol Given 3 Hours Post-study Treatment Dose at Visit 5/Day 28

  Baseline and Day 28

Study Arms (3)

Treatment Phase A

EXPERIMENTAL

Eligible subjects will enter a 4-week run-in period and will receive fluticasone propionate/salmeterol. Subjects will then be randomized to receive fluticasone furoate 100 mcg, fluticasone furoate/umeclidinium bromide 100/15.6 mcg, fluticasone furoate/umeclidinium bromide 100/62.5 mcg, fluticasone furoate/umeclidinium bromide 100/125 mcg, fluticasone furoate/umeclidinium bromide 100/250 mcg, or fluticasone furoate/vilanterol 100/25 mcg, respectively for 4 weeks

Drug: FF; Drug: UMEC; Drug: VI

Treatment Phase B

EXPERIMENTAL

Subjects completing Treatment Phase A will be randomized to receive either fluticasone furoate/umeclidinium bromide100/250 mcg or fluticasone furoate/umeclidinium bromide/vilanterol 100/250/25 mcg for 1 week.

Drug: FF; Drug: UMEC; Drug: VI

Treatment Phase C

EXPERIMENTAL

Subjects completing Treatment Phase B will be randomized to receive either the same treatment as in Treatment Phase B, or the same treatment minus the umeclidinium bromide component, for 1 week.

Drug: FF; Drug: UMEC; Drug: VI

Interventions

FF DRUG

Fluticasone furoate is available as fluticasone furoate inhalation powder (100 mcg per blister), combination of fluticasone furoate/umeclidinium bromide inhalation powder (fluticasone furoate: 100 mcg per blister, umeclidinium bromide: 15.6, 62.5, 125, or 250 mcg per blister) and combination of fluticasone furoate/vilanterol inhalation powder (fluticasone furoate: 100 mcg per blister, vilanterol: 25 mcg per blister)

Treatment Phase A; Treatment Phase B; Treatment Phase C

UMEC DRUG

Umeclidinium bromide is available as combination of fluticasone furoate/umeclidinium bromide inhalation powder (fluticasone furoate: 100 mcg per blister, umeclidinium bromide: 15.6, 62.5, 125, or 250 mcg per blister)

Treatment Phase A; Treatment Phase B; Treatment Phase C

VI DRUG

Vilanterol is available as vilanterol inhalation powder (25 mcg per blister) and combination of fluticasone furoate/vilanterol inhalation powder (fluticasone furoate: 100 mcg per blister, vilanterol: 25 mcg per blister)

Treatment Phase A; Treatment Phase B; Treatment Phase C

Eligibility Criteria

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

You may qualify if:

• years of age or older
• COPD with evidence of an asthmatic component as demonstrated by spirometry, reversibility and current therapy at screening as follows:
• Post-bronchodilator morning (AM) FEV1 \>=50% and \<=80% of the predicted normal value at Visit 1
• Pre- and post-bronchodilator FEV1/FVC ratio \<0.7.
• Demonstrated reversibility by \>=12% and \>=200 mL increase in FEV1 following albuterol at Visit 1.
• A need for regular controller therapy (i.e., inhaled corticosteroids alone or in combination with a long-acting beta-agonist or leukotriene modifier, etc.) for a minimum of 12 weeks prior to Visit 1.
• Outpatient subjects who are smokers or non-smokers.

You may not qualify if:

• History of life-threatening respiratory event within the last 5 years.
• Unresolved respiratory infection
• Recent Severe COPD or Asthma Exacerbation
• Risk factors for pneumonia
• Hospitalization for pneumonia within 3 months
• Concurrent respiratory disease other than chronic obstructive pulmonary disease or asthma.
• Other uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
• Viral hepatitis or HIV
• Current or chronic history of liver disease, known hepatic or biliary abnormalities
• Drug or milk protein allergy
• Administration of prescription or over-the-counter medication that would significantly affect the course of COPD or asthma, or interact with study drug
• Subjects with lung volume reduction surgery within 12 months prior to screening.
• Use of long-term oxygen therapy (LTOT)
• Requirement for nebulized therapy
• Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (67)

GSK Investigational Site

Newport Beach, California, 92663, United States

Location

GSK Investigational Site

San Diego, California, 92117, United States

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GSK Investigational Site

Upland, California, 91786, United States

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GSK Investigational Site

Sunset, Louisiana, 70584, United States

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GSK Investigational Site

Minneapolis, Minnesota, 55407, United States

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GSK Investigational Site

Charlotte, North Carolina, 28207, United States

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GSK Investigational Site

Cincinnati, Ohio, 45231, United States

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GSK Investigational Site

Medford, Oregon, 97504, United States

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GSK Investigational Site

Gaffney, South Carolina, 29340, United States

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GSK Investigational Site

Greenville, South Carolina, 29615, United States

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GSK Investigational Site

Rock Hill, South Carolina, 29732, United States

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GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

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GSK Investigational Site

Union, South Carolina, 29379, United States

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GSK Investigational Site

Morgantown, West Virginia, 26505, United States

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GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1028AAP, Argentina

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GSK Investigational Site

San Rafael, Mendoza Province, 5600, Argentina

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GSK Investigational Site

Rosario, Santa Fe Province, S2000DBS, Argentina

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GSK Investigational Site

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

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GSK Investigational Site

Buenos Aires, C1426ABP, Argentina

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GSK Investigational Site

Mendoza, 5500, Argentina

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GSK Investigational Site

San Miguel de Tucumán, 4000, Argentina

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GSK Investigational Site

San Miguel de Tucumán, T4000IFL, Argentina

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GSK Investigational Site

Frankfurt am Main, Hesse, 60389, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

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GSK Investigational Site

Neu-Isenburg, Hesse, 63263, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30173, Germany

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GSK Investigational Site

Leipzg, Saxony, 04109, Germany

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GSK Investigational Site

Teuchern, Saxony-Anhalt, 06682, Germany

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GSK Investigational Site

Berlin, 10117, Germany

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GSK Investigational Site

Berlin, 10119, Germany

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GSK Investigational Site

Hamburg, 20253, Germany

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GSK Investigational Site

Bialystok, 15-044, Poland

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GSK Investigational Site

Bialystok, 15-430, Poland

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GSK Investigational Site

Katowice, 40-645, Poland

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GSK Investigational Site

Kielce, 25-734, Poland

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GSK Investigational Site

Lodz, 90-242, Poland

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GSK Investigational Site

Poznan, 60-214, Poland

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GSK Investigational Site

Sopot, 81-741, Poland

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GSK Investigational Site

Zgierz, 95-100, Poland

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GSK Investigational Site

Żnin, 88-400, Poland

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GSK Investigational Site

Bacau, 600252, Romania

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GSK Investigational Site

Bucharest, 020125, Romania

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GSK Investigational Site

Bucharest, 050159, Romania

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GSK Investigational Site

Cluj-Napoca, 400371, Romania

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GSK Investigational Site

Comuna Alexandru Cel Bun, 617507, Romania

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GSK Investigational Site

Craiova, Romania

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GSK Investigational Site

Piteşti, 110084, Romania

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GSK Investigational Site

Ploieşti, 100184, Romania

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GSK Investigational Site

Ploieşti, 100379, Romania

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GSK Investigational Site

Timișoara, 300310, Romania

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GSK Investigational Site

Blagoveshchensk, 675000, Russia

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GSK Investigational Site

Moscow, 105229, Russia

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GSK Investigational Site

Moscow, 115446, Russia

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GSK Investigational Site

Nizhny Novgorod, 603126, Russia

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GSK Investigational Site

Saint Petersburg, 194354, Russia

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GSK Investigational Site

Saint Petersburg, 194356, Russia

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GSK Investigational Site

Saint Petersburg, 198216, Russia

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GSK Investigational Site

Saratov, 410012, Russia

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GSK Investigational Site

Sestroretsk, 197706, Russia

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GSK Investigational Site

Dnipropetrovsk, 49006, Ukraine

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GSK Investigational Site

Dnipropetrovsk, 49051, Ukraine

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GSK Investigational Site

Kharkiv, 61002, Ukraine

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GSK Investigational Site

Kharkiv, 61124, Ukraine

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GSK Investigational Site

Kiev, 03680, Ukraine

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GSK Investigational Site

Kyiv, 02091, Ukraine

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GSK Investigational Site

Kyiv, 02232, Ukraine

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GSK Investigational Site

Kyiv, 3680, Ukraine

Location

Related Publications (1)

• Lee L, Kerwin E, Collison K, Nelsen L, Wu W, Yang S, Pascoe S. The effect of umeclidinium on lung function and symptoms in patients with fixed airflow obstruction and reversibility to salbutamol: A randomised, 3-phase study. Respir Med. 2017 Oct;131:148-157. doi: 10.1016/j.rmed.2017.08.013. Epub 2017 Aug 14.

  PMID: 28947022 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Asthma

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2014
• First Posted: June 16, 2014
• Study Start: July 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 18, 2015
• Last Updated: October 11, 2017
• Results First Posted: June 28, 2016

Record last verified: 2017-10

Locations

DE (9); US (14); PL (9); RU (9); AR (8); RO (10); UA (8)