Last updated: 11/07/2018 11:37:03
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) -Study 2
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A 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) -Study 2
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Change from Baseline (BL) in trough forced expiratory volume in one second (FEV1) at Day 85
Timeframe: Day 85
Secondary outcomes:
Change from Baseline in weighted mean (WM), 0-6 hour FEV1 obtained post-dose at Day 84
Timeframe: Day 84
Interventions:
Enrollment:
620
Primary completion date:
2014-21-04
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Siler TM, Kerwin E, Tombs L, Fahy WA, Naya I.Triple therapy of umeclidinium + inhaled corticosteroids/long-acting beta2 agonists for patients with COPD: pooled results of randomized placebo-controlled trials.Pulmonary Ther.2016;2(1):43-58.
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
fluticasone furoate/vilanterol, umeclidinium bromide
Collaborators
Not applicable
Study date(s)
October 2013 to April 2014
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
40+ years
Accepts healthy volunteers
No
- Type of subject: Outpatient.
- Informed Consent: A signed and dated written informed consent prior to study participation.
- Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
- Asthma: A current diagnosis of asthma.
Inclusion and exclusion 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 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)
- 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.
- QTc Criteria:
- QTc(F) <450 milliseconds (msec) or
- QTc(F) <480msec for patients with QRS duration >=120msec
- The QTc is the QT interval corrected for heart rate according to either Bazett’s formula (QTcB), Fridericia’s formula (QTcF), or another method, machine or manual overread.
- For subject eligibility and withdrawal, QTcF will be used.
- For purposes of data analysis, QTcF will be used as primary.
- The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
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 alpha-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 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.
- 12-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).
- No use within 48 hrs prior to Screening Visit 1 or thereafter at any time during the study: Theophyllines, Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton), Salmeterol and formoterol, ICS/LABA combinations (e.g., fluticasone propionate/salmeterol, mometasone furoate/formoterol fumarate, budesonide/formoterol fumarate), Oral beta2-agonists Long-acting.
- No use within 24 hrs prior to Screening Visit 1 or thereafter at any time during the study: Inhaled sodium cromoglycate or nedocromil sodium.
- No use within 12 hrs prior to Screening Visit 1 or thereafter at any time during the study: Oral beta2-agonists Short-acting.
- No use within 4 hrs prior to Screening Visit 1 or thereafter at any time during the study: Inhaled short acting beta2-agonists (use of study provided prn albuterol/salbutamol is permitted during the study, except in the 4-hour period prior to spirometry testing.), Inhaled short-acting anticholinergics, Inhaled short-acting anticholinergic/short-acting beta2-agonist combination products.
- No use within 30 days or 5 half lives whichever is longer prior to Screening Visit 1 or thereafter at any time during the study: Any other investigational drug.
- Prior enrolment in one of the replicate studies: subjects who have previously been assigned a subject number (enrolled) in study 200110 that is a replicate study of 200109.
- 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, or who will enter the acute phase of a pulmonary rehabilitation program during the study. 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, sub-investigator, 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.
Trial location(s)
Location
GSK Investigational Site
St. Charles, Missouri, United States, 63301
Status
Study Complete
Location
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70378
Status
Study Complete
Location
GSK Investigational Site
Osnabrueck, Niedersachsen, Germany, 49074
Status
Study Complete
Location
GSK Investigational Site
Spartanburg, South Carolina, United States, 29303
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30173
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45359
Status
Study Complete
Location
GSK Investigational Site
Greenville, South Carolina, United States, 29615
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45355
Status
Study Complete
Location
GSK Investigational Site
Ostrava - Poruba, Czech Republic, 70868
Status
Study Complete
Location
GSK Investigational Site
Charlotte, North Carolina, United States, 28207
Status
Study Complete
Location
GSK Investigational Site
Reinfeld, Schleswig-Holstein, Germany, 23858
Status
Study Complete
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 51069
Status
Study Complete
Location
GSK Investigational Site
Witten, Nordrhein-Westfalen, Germany, 58452
Status
Study Complete
Location
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19055
Status
Study Complete
Location
GSK Investigational Site
Huntington Beach, California, United States, 92647
Status
Study Complete
Location
GSK Investigational Site
Coeur D'Alene, Idaho, United States, 83814
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30159
Status
Study Complete
Location
GSK Investigational Site
Gaffney, South Carolina, United States, 29340
Status
Study Complete
Location
GSK Investigational Site
Orlando, Florida, United States, 32825
Status
Study Complete
Location
GSK Investigational Site
Koblenz, Rheinland-Pfalz, Germany, 56068
Status
Study Complete
Location
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39112
Status
Study Complete
Location
GSK Investigational Site
Kralupy nad Vltavou, Czech Republic, 278 01
Status
Study Complete
Location
GSK Investigational Site
Sunset, Louisiana, United States, 70584
Status
Study Complete
Location
GSK Investigational Site
Rock Hill, South Carolina, United States, 29732
Status
Study Complete
Location
GSK Investigational Site
Phoenix, Arizona, United States, 85006
Status
Study Complete
Location
GSK Investigational Site
Newport News, Virginia, United States, 23606
Status
Study Complete
Location
GSK Investigational Site
Dueren, Nordrhein-Westfalen, Germany, 52349
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2014-21-04
Actual study completion date
2014-21-04
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Participate in clinical trial
Additional information
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Click hereAccess to clinical trial data by researchers
Visit website