Cross-Over Study in Subjects With COPD, Evaluating Lung Function Response After Treatment With Once Daily Umeclidinium 62.5mcg, Vilanterol 25mcg, and Umeclidinium/Vilanterol 62.5/25mcg
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: Umeclidinium/Vilanterol 62.5/25 mcg; Umeclidinium 62.5 mcg; Vilanterol 25 mcg
Intervention description: Umeclidinium/Vilanterol 62.5/25 mcg once daily in the morning via novel dry powder inhaler (NDPI); Umeclidinium 62.5 mcg once daily in the morning via novel dry powder inhaler (NDPI); Vilanterol 25 mcg once daily in the morning via novel dry powder inhaler (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: 182.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: long-acting muscarinic antagonist; long-acting beta-agonist; Chronic Obstructive Pulmonary Disease; vilanterol; umeclidinium

Summary:

      The purpose of this study is to evaluate the lung function response to UMEC/VI, UMEC, and VI
      in individual patients using a cross-over design. This is a multicenter, randomized,
      double-blind, 3-way crossover study. Eligible subjects will be randomized to a sequence of
      UMEC 62.5mcg, VI 25mcg, and UMEC/VI 62.5/25mcg. All subjects will receive each treatment
      once-daily for 14 days, and each treatment will be separated by a 10-14 day washout period.
      There will be a 5-7 day run-in period prior to randomization.
    

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.

          -  COPD diagnosis: As defined by the American Thoracic Society/European Respiratory
             Society (ATS/ERS)

          -  Severity of disease: A pre- and post-salbutamol FEV1/FVC ratio of <0.70 and a pre- and
             post-salbutamol FEV1 of ≤ 70% of predicted normal values at Visit 1

          -  Smoking History: Current or former cigarette smokers with a history of cigarette
             smoking of ≥ 10 pack-years at Visit 1

          -  Female subject of non child-bearing potential OR a female subject of child bearing
             potential, with a negative pregnancy test at screening, and agreeing to consistently
             and correctly use one of the acceptable contraceptive methods

        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.

          -  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

          -  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 ECG finding from the 12-lead ECG conducted at
             Visit 1

          -  Screening Labs: Significantly abnormal finding from clinical chemistry or hematology
             tests at Visit 1 as determined by the study investigator.

          -  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 prohibited medications according to defined
             time intervals prior 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., 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