Study to compare umeclidinium/vilanterol compared with fluticasone propionate/salmeterol in COPD

• Register: EUCTR
• Last refreshed on: 5 August 2014
• Main ID: EUCTR2012-002156-16-RO
• Date of registration: 28/07/2014
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Limited
• Public title: Study to compare umeclidinium/vilanterol compared with fluticasone propionate/salmeterol in COPD
• Scientific title: A randomized, multi-center, double-blind, doubledummy, parallel group study to evaluate the efficacy and safety of umeclidinium/vilanterol compared with fluticasone propionate/salmeterol over 12 weeks in subjects with COPD. - GSK573719/GW642444 v Advair
• Date of first enrolment: 13/08/2014
• Target sample size: 710
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002156-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: DOUBLE DUMMY If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Chile, India, Mexico, Norway, Romania, Russian Federation, South Africa, United States

Contacts

• Name: GSK Clinical Support HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Limited

• Name: GSK Clinical Support HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Limited

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Type of subject: Outpatient
2. Informed Consent: A signed and dated written informed consent prior to study participation
3. Age: Subjects 40 years of age or older at Visit 1
4. 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. OR
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.
• Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent
(foam/gel/film/cream/suppository)
5. Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004] as follows:
Chronic obstructive pulmonary disease is a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of
the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.
6. 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)]. Previous 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.
7. Severity of disease: A pre and post-salbutamol FEV1/FVC ratio of <0.70 and a postsalbutamol FEV1 of =30% and =70% of predicted normal values calculated using
NHANES III reference equations at Visit 1 [Hankinson, 1999; Hankinson, 2010] .
8. Dyspnea: A score of =2 on the Modified Medical Research Council Dyspne
Exclusion criteria:
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study
2. Asthma: A current diagnosis of asthma
3. Other Respiratory Disorders: Known a-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 condition in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension,
sarcoidosis, or interstitial lung disease. Inactive tuberculosis in more than one lobe is exclusionary. Allergic rhinitis is not exclusionary.
4. 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.
5. Contraindications: A history of allergy or hypersensitivity to any
anticholinergic/muscarinic receptor antagonist, beta2-agonist, corticosteroid, lactose/milk protein or magnesium stearate or a medical condition such as narrowangle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician contraindicates study participation or use of an
inhaled anticholinergic.
6. Hospitalization: Hospitalization for pneumonia within 12 weeks prior to Visit 1
7. History of COPD Exacerbation: A documented history of at least one COPD exacerbation in the 12 months prior to Visit 1 that required either oral corticosteroids, antibiotics, and/or hospitalization. Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence.
8. Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1)
9. 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 (Section 11.4). The study investigator will determine the medical significance of any ECG abnormalities not listed in Appendix 4.
10. Medication Prior to Spirometry: Unable to withhold salbutamol for the 4 hour period required prior to spirometry testing at each study visit
11. Medications Prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1: '(see protocol Section 4.3)'.
12. 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.
13. Nebulized Ther

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 17.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855

Intervention(s)

Product Name: Umeclidinium/Vilanterol
Product Code: GSK573719/GW642444
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Umeclidinium Bromide
CAS Number: 869113-09-7
Current Sponsor code: GSK573719
Other descriptive name: GSK573719
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 62.5-
INN or Proposed INN: Vilanterol Trifenatate
CAS Number: 503070-58-4
Current Sponsor code: GW642444
Other descriptive name: Vilanterol trifenatate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Inhalation powder, pre-dispensed
Route of administration of the placebo: Inhalation use

Trade Name: Seretide
Product Name: Fluticasone propionate/salmeterol
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Fluticasone propionate
CAS Number: 80474-14-2
Other descriptive name: FLUTICASONE PROPIONATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 250-
INN or Proposed INN: SALMETEROL
CAS Number: 89365-50-4
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Inhalation powder, pre-dispensed
Route of administration of the placebo: Inhalation use
Pharmaceutical form of the placebo: Inhalation powder, pre-dispensed
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 24-hour weighted-mean serial FEV1 on Treatment Day 84. This weighted mean is calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5 and 15 minutes and 1, 3, 6, 9, 12 (pre evening dose), 13, 15, 18, 23, and 24 hours after the morning dose.

Secondary Objective: N/A

Main Objective: Primary Objective:

Compare the efficacy and safety of UMEC/VI Inhalation Powder (62.5/25mcg oncedaily) with fluticasone propionate/salmeterol (250/50mcg twice-daily) over 12 weeks in subjects with COPD who have a history of infrequent COPD exacerbations

Primary end point(s): '24-hour weighted mean serial FEV1on Treatment Day 84.'

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Trough FEV1 on Day 85, defined as the mean of the FEV1 values obtained 23 and 24 hours after morning dosing on Day 84.
Weighted Mean FEV1 over 0-6 hours post-dose on Day 1 Trough FEV1 at Day 28, Day 56, and Day 84 Rescue salbutamol use (percentage of rescue-free days and puffs/day) Proportion of subjects achieving an increase in FEV1 of =12% and =200mL above baseline at any time during 0-6 hours post-dose on Treatment Day 1. Proportion of subjects achieving an increase of =100mL above baseline in trough FEV1 Peak FEV1
Serial FEV1 over 0 to 6 hours post-dose on Day 1 Serial FEV1 over 0 to 24 hours post-dose on Day 84 Serial FVC at Day 1 (0-6 hours post-dose) and Day 84 (0-24 hours post-dose) Trough FVC at Day 28, Day 56, Day 84 and Day 85 . For further details refer to the protocol.

Secondary end point(s): Trough and Weighted Mean FEV1
Rescue salbutamol use (percentage of rescue-free days and puffs/day)
Proportion of subjects achieving an increase in FEV1 of = 12% and =200mL above baseline Proportion of subjects achieving an increase of = 100mL above baseline in trough FEV1
Peak and serial FEV1
Serial, trough and weighted mean FVC
TDI focal score
Incidence of adverse events (AEs)
COPD exacerbations
Vital signs
EQ-5D health outcome assessment
COPD Assessment Test (CAT)
St. George’s Respiratory Questionnaire for COPD patients (SGRQ-C)

Secondary ID(s)

DB2114951

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Limited