Clinical trial NCT01772134: Efficacy and Safety of the Addition of Fluticanse Propionate/Salmeterol (250/50mcg) Twice-daily to 2 Doses of Umeclidinium Bromide (62.5 or 125mcg) Once-daily Over 12 Weeks
Official title: A Multicenter, Randomized, Double-blind, Parallel-group Study to Evaluate the Efficacy and Safety of the Addition of Umeclidinium Bromide (62.5mcg) Once-daily to Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily, Umeclidinium Bromide (125mcg) Once-daily to Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily Versus Placebo to Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily Over 12 Weeks With COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-01-21
Enrollment: 617
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this 12 week study is to evaluate the effects of the addition of umeclidinium bromide (62.5mcg) once-daily to fluticanse propionate/salmeterol (250/50mcg) twice-daily, umeclidinium bromide (125mcg) once-daily to fluticanse propionate/salmeterol (250/50mcg) twice-daily versus placebo to fluticanse propionate/salmeterol (250/50mcg) twice-daily on lung function, COPD-related health status assessments and safety in COPD subjects.

Detailed description: This is a mutlicenter, randomized, double-blind, parallell-group study. Subejcts who meet the eligibility criteria at screening and meet the randomization criteria at the end of a 4 week run-in period will enter a 12 week treatment period. There will be a 7 day follow-up period after the treatment period.

Eligibility criteria: Inclusion Criteria:

* -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 if of non-childbearing potential, or if of child bearing potential, has a negative serum pregnancy test at screening, and agrees to one of the acceptable contraceptive methods listed in the protocol, used consistenty and correctly.
* Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society.
* Smoking History: Current or former cigarette smokers with a history of cigarette smoking of ≥10 pack-years \[number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. 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.
* Severity of Disease: A pre and post-albuterol/salbutamol FEV1/FVC ratio of \<0.70 and a pre and post-albuterol/salbutamol FEV1 of ≤70% of predicted normal values at Visit 1 (Screening) calculated using Nutrition Health and Examination Survey (NHANES) III reference equations.
* Dyspnea: A score of ≥2 on the mMRC Dyspnea Scale at Visit 1.

Exclusion Criteria:

* Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
* Asthma: A current diagnosis of asthma.
* Other Respiratory Disorders: Known α-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions. A subject who, in the opinion of the investigator, has any other significant respiratory conditions in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease.
* Other Diseases/Abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for \<5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
* 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 anticholingeric.
* Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
* Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1.
* 12-Lead ECG: An abnormal and 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.

Specific ECG findings that preclude subject eligibility are listed in Appendix 4. The study investigator will determine the medical significance of any ECG abnormalities not listed in Appendix 4.

* Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
* Medications Prior to Screening: Use of the medications listed in the protocol according to protocol-specific times prio to visit 1.
* Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., ≤12 hours per day) is not exclusionary.
* Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulized therapy.
* Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
* Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
* Affiliation with Investigator Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, subinvestigator, study coordinator, or employee of the participating investigator.
* Inability to read: In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete a questionnaire.

Primary outcomes:
measure: Change From Baseline in the Trough Forced Expiratory Volume in One Second (FEV1) on Day 85
timeFrame: Baseline and Day 85
Secondary outcomes:
measure: Change From Baseline in Weighted Mean 0-6 Hour FEV1 Obtained Post-dose at Day 84
timeFrame: Baseline and Day 84
measure: Change From Baseline in the Mean Percentage of Rescue-free Days Over Weeks 1-12
timeFrame: Baseline and Weeks 1-12
measure: Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Weeks 1-12
timeFrame: Baseline and Weeks 1-12
Other outcomes:
Locations:
city: Jasper
country: United States
facility: GSK Investigational Site
state: Alabama
city: Clearwater
country: United States
facility: GSK Investigational Site
state: Florida
city: Ormond Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Lafayette
country: United States
facility: GSK Investigational Site
state: Indiana
city: New Orleans
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Edina
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Easley
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Union
country: United States
facility: GSK Investigational Site
state: South Carolina
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Morgantown
country: United States
facility: GSK Investigational Site
state: West Virginia
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: GSK Investigational Site
state: Manitoba
city: Bay Roberts
country: Canada
facility: GSK Investigational Site
state: Newfoundland and Labrador
city: Truro
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Burlington
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Gatineau
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Mirabel
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: St-Charles-Borromée
country: Canada
facility: GSK Investigational Site
state: Quebec
city: St-Romuald
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Trois Rivières
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Sinsheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Stuttgart
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Bamberg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Schwabach
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Gelnhausen
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Kassel
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Schwerin
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Weyhe-Leeste
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Dueren
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Goch
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Witten
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koblenz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Magdeburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Teuchern
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzg
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Luebeck
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Reinfeld
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Gera
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Schmoelln
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Bucheon-si,
country: Korea, Republic of
facility: GSK Investigational Site
city: Cheongju, Chungcheongbuk-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Kangwon-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon, Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: