Study to Compare the Addition of Umeclidinium Bromide (UMEC) to Fluticasone Furoate (FF)/Vilanterol (VI), With Placebo Plus FF/VI in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

NCT01957163 | Completed Phase 3 Results

• 1 other identifier: 200109
• Study Type: interventional
• Target: 619
• Locations: 5 countries
• Sites: 53

Brief Summary

After screening, subjects will enter a 4 week open-label run-in period with fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg administered once daily via dry powder inhaler (DPI). Subjects will then be randomized to receive any one of the 3 treatments (umeclidinium bromide \[UMEC\] \[62.5 mcg\] administered once daily via a DPI; OR UMEC \[125 mcg\] administered once daily via a DPI; OR matching placebo administered once daily via a DPI), while continuing treatment with open label FF/VI 100/25 mcg during a 12-week treatment period. There will be a total of eight scheduled clinic visits at Pre-Screening (Visit0), Screening (Visit 1), blinded treatment Day 1(Visit2), 2(Visit3), 28 (Visit4), 56 (Visit5), 84 (Visit6) and 85 (Visit7). A follow-up phone contact will be conducted approximately 7 days after the last clinic visit. The total duration of subject participation in the study from Screening to Follow-up will be approximately 17 weeks.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

dry powder inhaler; fluticasone furoate/vilanterol; umeclidinium bromide; safety; long acting beta2- receptor agonist; long acting muscarininc receptor antagonist; efficacy; COPD; inhaled corticosteroid

Outcome Measures

Primary Outcomes (1)

• Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) at Day 85

  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 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84. Analysis was performed using a mixed model repeated measures (MMRM) with covariates of treatment, Baseline FEV1, smoking status, Day, treatment, Day by baseline interaction and Day by treatment interaction, Day being nominal. Baseline FEV1 is the mean of the two assessments made at 30 and 5 minutes (min) pre-dose on Day 1. The change from baseline value is the difference between the on-treatment value and the baseline value.

  Day 85

Secondary Outcomes (1)

• Change From Baseline in Weighted Mean (WM), 0-6 Hour FEV1 Obtained Post-dose at Day 84

  Day 84

Study Arms (3)

FF/VI 100/25 mcg + UMEC (62.5mcg)

EXPERIMENTAL

Subjects received one inhalation of FF/VI 100/25 mcg via a DPI followed by one inhalation UMEC (62.5mcg) via DPI once-daily in the morning for 12 weeks.

Drug: FF; Drug: VI; Drug: UMEC

FF/VI 100/25 mcg + UMEC (125mcg)

EXPERIMENTAL

Subjects received one inhalation of FF/VI 100/25 mcg via DPI followed by one inhalation of UMEC (125mcg) via a DPI once-daily in the morning for 12 weeks.

Drug: FF; Drug: VI; Drug: UMEC

FF/VI 100/25 mcg + Placebo

EXPERIMENTAL

Subjects received one inhalation of FF/VI 100/25 mcg via DPI followed by one inhalation of matching placebo via a DPI once-daily in the morning for 12 weeks.

Drug: FF; Drug: VI; Drug: Placebo

Interventions

FF DRUG

Dry white powder containing 100mcg of Fluticasone Furoate blended with lactose per blister was administered by DPI.

FF/VI 100/25 mcg + Placebo; FF/VI 100/25 mcg + UMEC (125mcg); FF/VI 100/25 mcg + UMEC (62.5mcg)

VI DRUG

Dry white powder containing 25mcg of Vilanterol micronised drug (as the 'M' salt triphenylacetate) blended with lactose and magnesium stearate per blister was administered by DPI.

FF/VI 100/25 mcg + Placebo; FF/VI 100/25 mcg + UMEC (125mcg); FF/VI 100/25 mcg + UMEC (62.5mcg)

UMEC DRUG

Umeclidinium bromide in a powder blend with lactose and magnesium stearate was used at two different doses 62.5mcg and 125mcg.

FF/VI 100/25 mcg + UMEC (125mcg); FF/VI 100/25 mcg + UMEC (62.5mcg)

Placebo DRUG

The matching placebo DPI identical in appearance to the inhaler containing active study medication.

FF/VI 100/25 mcg + Placebo

Eligibility Criteria

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

You may qualify if:

• Type of subject: Outpatient.
• Informed Consent: A signed and dated written informed consent prior to study participation.
• Age: Subjects 40 years of age or older at Visit 1.
• Gender: Male or female subjects.
• 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.
• 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 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.

You may not qualify if:

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
• Asthma: A current diagnosis of asthma.
• Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, sympathomimetic, corticosteroid (intranasal, inhaled or systemic) 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 Long acting muscarinic antagonist (LAMA), Long acting beta agonist (LABA) or Inhaled corticosteroids (ICS).
• Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
• Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit 1.
• Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1.
• Lead ECG: An abnormal and clinical significant ECG finding from the 12-lead ECG conducted at Visit 1. Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. The study investigator will determine the medical significance of any ECG abnormalities.
• Clinically significant and abnormal laboratory finding at Screening (Visit1). After discussion with the Medical Monitor, the investigator may have the option to verify the abnormal lab result prior to Visit2
• Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
• Excluded Medications: Use of the following medications are not permitted within the defined time intervals prior to Visit 1and throughout the study:
• No use within 12 weeks prior to Screening Visit 1 or thereafter at any time during the study: Depot corticosteroids.
• No use within 6 weeks prior to Screening Visit 1 or thereafter at any time during the study: Systemic, oral or parenteral corticosteroids (Intra-articular corticosteroid injections are permitted.), Antibiotics (for lower respiratory tract infection), Cytochrome P450 3A4 strong inhibitors.
• No use within 14 days prior to Screening Visit 1 or thereafter at any time during the study: Phosphodiesterase 4 inhibitors (roflumilast).
• No use within 10 days prior to Screening Visit 1 or thereafter at any time during the study: Olodaterol and Indacaterol.
• No use within 7 days prior to Screening Visit 1 or thereafter at any time during the study: Long acting muscarinici antagonists (tiotropium, aclidinium, glycopyrronium).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (53)

GSK Investigational Site

Jasper, Alabama, 35501, United States

Location

GSK Investigational Site

Clearwater, Florida, 33765-2616, United States

Location

GSK Investigational Site

Tampa, Florida, 33603, United States

Location

GSK Investigational Site

New Orleans, Louisiana, 70115, 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

Easley, South Carolina, 29640, 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

Union, South Carolina, 29379, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Abingdon, Virginia, 24210, United States

Location

GSK Investigational Site

Morgantown, West Virginia, 26505, United States

Location

GSK Investigational Site

Buenos Aires, C1424BSF, Argentina

Location

GSK Investigational Site

Buenos Aires, C1425BEN, Argentina

Location

GSK Investigational Site

Buenos Aires, C1425FVH, Argentina

Location

GSK Investigational Site

Buenos Aires, C1426ABP, Argentina

Location

GSK Investigational Site

Mendoza, 5500, Argentina

Location

GSK Investigational Site

Mendoza, M5500CCG, Argentina

Location

GSK Investigational Site

San Miguel de Tucumán, 4000, Argentina

Location

GSK Investigational Site

Winnipeg, Manitoba, R2K 3S8, Canada

Location

GSK Investigational Site

Truro, Nova Scotia, B2N 1L2, Canada

Location

GSK Investigational Site

Greater Sudbury, Ontario, P3E 1H5, Canada

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GSK Investigational Site

Toronto, Ontario, M3H 5S4, Canada

Location

GSK Investigational Site

Toronto, Ontario, M4V 1R3, Canada

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GSK Investigational Site

Toronto, Ontario, M5G 1N8, Canada

Location

GSK Investigational Site

Gatineau, Quebec, J8Y 6S8, Canada

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GSK Investigational Site

Mirabel, Quebec, J7J 2K8, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2R 1V6, Canada

Location

GSK Investigational Site

Québec, Quebec, G1V 4G5, Canada

Location

GSK Investigational Site

Saint-Charles-Borromée, Quebec, J6E 2B4, Canada

Location

GSK Investigational Site

St-Romulad, Quebec, G6W 5M6, Canada

Location

GSK Investigational Site

Quillota, Región de Valparaíso, 2260000, Chile

Location

GSK Investigational Site

Concepción, Región Del Biobio, 4070038, Chile

Location

GSK Investigational Site

Puente Alto - Santiago, Región Metro de Santiago, 8207257, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7500692, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7500710, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7510186, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7880047, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 8910131, Chile

Location

GSK Investigational Site

Talca, Región Metro de Santiago, 3460001, Chile

Location

GSK Investigational Site

Santiago, 8380453, Chile

Location

GSK Investigational Site

Santiago, 8910131, Chile

Location

GSK Investigational Site

Viña del Mar, 2520594, Chile

Location

GSK Investigational Site

Bacau, 600252, Romania

Location

GSK Investigational Site

Bucharest, 010457, Romania

Location

GSK Investigational Site

Bucharest, 020125, Romania

Location

GSK Investigational Site

Bucharest, 030303, Romania

Location

GSK Investigational Site

Cluj-Napoca, 400371, Romania

Location

GSK Investigational Site

Codlea, 505100, Romania

Location

GSK Investigational Site

Râmnicu Vâlcea, 240564, Romania

Location

GSK Investigational Site

Suceava, 720284, Romania

Location

GSK Investigational Site

Timișoara, 300310, Romania

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

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

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2013
• First Posted: October 8, 2013
• Study Start: October 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: November 9, 2017
• Results First Posted: November 25, 2014

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

US (13); CL (12); RO (9); CA (12); AR (7)