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)
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Umeclidinium 62.5 mcg; Vilanterol 25 mcg; Umeclidinium/Vilanterol 62.5/25 mcg
Intervention description: Umeclidinium 62.5 mcg once daily in the morning via NDPI.; Vilanterol 25 mcg once daily in the morning via NDPI.; Umeclidinium/Vilanterol 62.5/25 mcg once daily in the morning via NDPI.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 207.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Long-acting beta-agonist; Chronic Obstructive Pulmonary Disease; Umeclidinium; Long-acting muscarinic antagonist; Vilanterol

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.