Clinical trial NCT02014480: A Cross-Over Study to Evaluate Lung Function Response After Treatment With Umeclidinium (UMEC) 62.5 Micrograms (mcg), Vilanterol (VI) 25 mcg, and Umeclidinium/Vilanterol (UMEC/VI) 62.5/25 mcg Once-Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Official title: A Randomized, Double-Blind, 3-Way, Cross-Over Study to Evaluate Lung Function Response After Treatment With Umeclidinium 62.5 mcg, Vilanterol 25 mcg, and Umeclidinium/Vilanterol 62.5/25 mcg Once-Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Long-acting beta-agonist
Chronic Obstructive Pulmonary Disease
Umeclidinium
Long-acting muscarinic antagonist
Vilanterol
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-12-18
Enrollment: 207
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, double-blind, 3-way crossover study to evaluate the lung function response to UMEC 62.5 mcg, VI 25 mcg, and UMEC/VI 62.525 mcg, administered once-daily via a novel dry powder inhaler (NDPI) over 14 days in subjects with COPD.

The study consisted of Run in Phase (5 to 7 days), Treatment Phase (made up of 3 treatment periods of 14 days each separated by 10 to 14 days Washout Period) and Follow-up Phase (7 to 9 days after completion of final visit or premature discontinuation). Eligible subjects will be randomized to a sequence of UMEC 62.5 mcg, VI 25 mcg, and UMEC/VI 62.5/25 mcg such that all subjects will receive each treatment.

Serial spirometry assessments will be conducted on Day 1 and Day 14 and trough spirometry will be conducted on Day 2 and Day 15 of each treatment period. On Day 1 and 14 of each treatment period vital signs will be assessed and adverse event (AE)s will be recorded throughout the total duration of the study (approximately 12 weeks).


Eligibility criteria: Inclusion Criteria:

* Type of Patient: 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. 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 acceptable contraceptive methods used consistently 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 at Visit 1.
* Severity of Disease: A pre- and post-salbutamol FEV1/forced vital capacity (FVC) ratio of \<0.70 and a pre- and post-salbutamol FEV1 of \<=70% of predicted normal values at Visit 1 calculated using Nutrition Health and Examination Survey (NHANES) III reference Equations.

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 condition in addition to COPD, should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease. Allergic rhinitis is not exclusionary. 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).
* Contraindications: A history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as of 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 anticholinergic.
* 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 electrocardiogram (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.
* Medication Prior to Spirometry: Unable to withhold salbutamol for the 4 hour period required prior to spirometry testing at each study visit and at each spirometry test performed at home.
* Medications Prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1: Depot corticosteroids (12 weeks), oral or parenteral corticosteroids (6 weeks), antibiotics (for lower respiratory tract infection) (6 weeks), cytochrome P450 3A4 strong inhibitors2 (6 weeks), long-acting beta agonist (LABA)/ inhaled corticosteroid (ICS) combination products if LABA/ICS therapy is discontinued completely (30 days), use of ICS at a dose \>1000 mcg/day of fluticasone propionate or equivalent (30 days), initiation or discontinuation of ICS use (30 days), tiotropium (7 days), roflumilast (14 days), theophyllines (48 hours), oral leukotriene inhibitors (zafirlukast, montelukast, zileuton) (48 hours), oral beta-agonists long-acting (48 hours), short-acting (12 hours), inhaled long acting beta2-agonists (LABA, e.g., salmeterol, formoterol, indacaterol) (48 hours), LABA/ICS combination products only if discontinuing LABA therapy and switching to ICS monotherapy (48 hours for the LABA component), inhaled sodium cromoglycate or nedocromil sodium (24 hours), inhaled short acting beta2-agonists (4 hours), inhaled short-acting anticholinergic/short-acting beta2-agonist combination products (4 hours) and any other investigational medication 30 days or within 5 drug half-lives (whichever is longer).
* 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., salbutamol, ipratropium bromide) 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: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.
* 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 (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type
timeFrame: Baseline and Day 14 of each treatment period (up to study day 85)
Secondary outcomes:
measure: Number of Participants (Par.) Who Were Responsive to UMEC/VI, UMEC or, VI According to FEV1 at Day 1 of Each Treatment Period (TP)
timeFrame: Baseline (BL) and 0-6 hours post-dose (15 minutes, 30 minutes, and 1, 3, and 6 hours post-dose) on Day 1 of each treatment period (up to study day 66)
measure: Number of Participants With a Larger Change From Baseline in 0-6 Hour Weighted Mean FEV1 at Day 14 of Each Treatment Period With UMEC/VI Compared With UMEC and VI Alone
timeFrame: Baseline and Day 14 of each treatment period (up to study day 85)
measure: Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period
timeFrame: Baseline and Day 15 of each treatment period (up to study day 81)
Other outcomes:
Locations:
city: Humenne
country: Slovakia
facility: GSK Investigational Site
city: Kralovsky Chlmec
country: Slovakia
facility: GSK Investigational Site
city: Poprad
country: Slovakia
facility: GSK Investigational Site
city: Sala
country: Slovakia
facility: GSK Investigational Site
city: Vrable
country: Slovakia
facility: GSK Investigational Site
city: Donetsk
country: Ukraine
facility: GSK Investigational Site
city: Donetsk
country: Ukraine
facility: GSK Investigational Site
city: Ivano-Frankivsk
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kiev
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Mykolayiv
country: Ukraine
facility: GSK Investigational Site
city: Poltava
country: Ukraine
facility: GSK Investigational Site
city: Simferopol
country: Ukraine
facility: GSK Investigational Site
city: Sympheropol
country: Ukraine
facility: GSK Investigational Site
city: Vinnytsia
country: Ukraine
facility: GSK Investigational Site
city: Vinnytsia
country: Ukraine
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: