Study Evaluating the Efficacy and Safety of Fluticasone Furoate/Vilanterol Inhalation Powder (FF/VI) Compared With Vilanterol Inhalation Powder (VI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration
Intervention: Fluticasone Furoate/Vilanterol; Vilanterol
Intervention description: 100 mcg FF micronized drug blended with lactose per blister in one strip and 25 mcg VI micronized drug blended with lactose and magnesium stearate per blister in another strip, administered together by ELLIPTA™ inhaler; 25 mcg of Vilanterol micronized drug (as the 'M' salt triphenylacetate) blended with lactose and magnesium stearate per blister in one strip and lactose in another strip, administered together by ELLIPTA™ inhaler
Intervention MeSH terms: Fluticasone; Xhance
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1621.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: COPD; Fluticasone Furoate (FF); Vilanterol (VI); Dry Powder Inhaler

Summary:

      This is a Phase IIIa, multicenter, randomized, stratified (reversibility status),
      double-blind, parallel-group study to evaluate the efficacy and safety of FF/VI 100/25
      micrograms (mcg) once daily (QD) compared with VI 25 mcg QD, administered in the morning via
      the ELLIPTA™ inhaler. The primary objective of this study is to evaluate the contribution on
      lung function (as measured by trough forced expiratory volume in one second [FEV1]) of FF 100
      mcg to the FF/VI 100/25 mcg QD combination by comparison of the latter with VI 25 mcg QD and
      the safety of FF/VI 100/25 mcg over a 12-week treatment period in subjects with COPD.
      ELLIPTA™ is a registered trademark of GlaxoSmithKline.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type of subject: Outpatient

          -  Informed consent: Subjects must give their signed and dated written informed consent
             to participate

          -  Gender: Male subjects or female subjects. Female subjects must be post-menopausal or
             using a highly effective method for avoidance of pregnancy. The decision to include or
             exclude women of childbearing potential may be made at the discretion of the
             investigator in accordance with local practice in relation to adequate contraception.

          -  Age: >=40 years of age at Screening (Visit 1)

          -  COPD diagnosis: Subjects with a clinical history of COPD in accordance with the
             definition by the American Thoracic Society/European Respiratory Society: COPD is a
             preventable and treatable disease 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 is also
             associated with significant systemic consequences.

          -  Severity of disease: Subjects with a measured post-albuterol (salbutamol) FEV1/ Forced
             Vital Capacity (FVC) ratio of <=0.70 and FEV1 >=30 to <=70 percent of predicted normal
             values using Global Lung Function Initiative 2012 reference equations at Screening
             (Visit 1).

          -  Tobacco use: Subjects with a current or prior history of >=10 pack-years of cigarette
             smoking at Screening (Visit 1). Former smokers are defined as those who have stopped
             smoking for at least 6 months prior to Visit 1.

          -  History of COPD exacerbation: A documented history (e.g., medical record verification)
             of at least one COPD exacerbation in the 12 months prior to Screening (Visit 1) that
             required either systemic/oral corticosteroids, antibiotics and/or hospitalization.

          -  Current symptoms of COPD: A Subject Diary combined symptom score (combination of
             breathlessness, cough, sputum, and night time awakenings requiring treatment with
             albuterol [salbutamol]) of >=4 on at least 5 of the 7 days immediately preceding Visit
             2 (Randomization)

          -  QTc Criteria: QTc <450 msec or QTc <480 msec for patients with bundle branch block.

        Exclusion Criteria:

          -  Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant
             during the study.

          -  Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of
             asthma are eligible if they have a current diagnosis of COPD).

          -  Other respiratory disorders: Subjects with alpha1-antitrypsin deficiency as the
             underlying cause of COPD as the underlying cause of COPD, active tuberculosis, lung
             cancer, bronchiectasis (Note: focal bronchiectasis is not exclusionary), sarcoidosis,
             pulmonary fibrosis (Note: focal fibrotic pulmonary lesions are not exclusionary),
             primary pulmonary hypertension, interstitial lung diseases, or other active pulmonary
             diseases.

          -  Lung resection: Subjects with lung volume reduction surgery within the 12 months prior
             to Screening (Visit 1).

          -  Chest X-ray (or computed tomography [CT] scan): Subjects with a chest X-ray (or CT
             scan) that reveals evidence of clinically significant abnormalities not believed to be
             due to the presence of COPD. A chest X-ray must be taken at Screening (Visit 1) if a
             chest X-ray or CT scan is not available within 1 year prior to Screening (Visit 1).

          -  Hospitalization: Subjects who are hospitalized due to poorly controlled COPD that has
             not resolved at least 4 weeks prior to Screening (Visit 1) and at least 6 weeks
             following the last dose of systemic corticosteroids.

          -  Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the
             occurrence of any of the following in the 6 weeks prior to Screening (Visit 1): Acute
             worsening of COPD that is managed by subject with systemic corticosteroids or
             antibiotics or that requires treatment prescribed by a physician.

          -  Lower respiratory tract infection: Subjects with lower respiratory tract infection
             that required the use of antibiotics within 6 weeks prior to Screening (Visit 1).

          -  COPD exacerbation/lower respiratory tract infection during the Run-In Period: Subjects
             who experience a moderate/severe COPD exacerbation (As per definition of "COPD
             Exacerbations and Pneumonia" in protocol) and/or a lower respiratory tract infection
             (including pneumonia) during the Run-In Period.

          -  Abnormal, clinically significant laboratory finding: Subjects who have an abnormal
             clinical significant finding in any liver chemistry test at Screening (Visit 1) or
             upon repeat prior to randomization.

          -  Abnormal, clinically significant 12-lead ECG at Screening (Visit 1): Subjects who have
             an abnormal, clinically significant 12-Lead electrocardiogram (ECG) finding at
             Screening (Visit 1) or upon repeat prior to randomization.

          -  Other diseases/abnormalities: Subjects with historical or current evidence of
             clinically significant and unstable disease such as cardiovascular (e.g., patients
             requiring implantable cardioverter-defibrillators (ICD), pacemaker requiring a rate
             set >60 beats per minute (bpm), uncontrolled hypertension, New Your Heart Association
             Class IV, known left ventricular ejection fraction <30 percent) neurological,
             psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes
             or thyroid disease), peptic ulcer disease, or hematological abnormalities.

          -  Liver disease: Subjects who have unstable liver disease (as defined by the presence of
             ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric
             varices or persistent jaundice), cirrhosis, known biliary abnormalities (with the
             exception of Gilbert's syndrome or asymptomatic gallstones). Note: Subjects with
             chronic stable hepatitis B and C are eligible if the subject otherwise meets entry
             criteria (e.g., presence of hepatitis B surface antigen or positive hepatitis C test
             result within 3 months of screening). However, subjects with chronic stable hepatitis
             B are excluded if significant immunosuppressive or cytotoxic agents are administered,
             due to risk of hepatitis B reactivation, unless the hepatitis B antivirals are
             administered as outlined in the Chronic Hepatitis B American Association for the Study
             of Liver Diseases' (AASLD) Practice Guidelines.

          -  Cancer: Subjects with carcinoma that has not been in complete remission for at least 5
             years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell
             carcinoma of the skin would not be excluded if the subject has been considered cured
             within 5 years since diagnosis.

          -  Contraindications: Subjects with a history of allergy or hypersensitivity to any of
             the study medications (e.g. beta-agonists, corticosteroids) or components of the
             inhalation powder (e.g., lactose, magnesium stearate). In addition, subjects with a
             history of severe milk protein allergy that, in the opinion of the investigator,
             contraindicates the subject's participation will also be excluded.

          -  Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug
             abuse within the last 2 years

          -  Medication prior to spirometry: Subjects who are medically unable to withhold their
             albuterol (salbutamol) or their ipratropium bromide for the 4-hour period required
             prior to spirometry testing at each study visit.

          -  Additional medication: Use of certain medications such as bronchodilators and
             corticosteroids for the protocol-specific times prior to Visit 1 (the Investigator
             will discuss the specific medications)"

          -  Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or
             nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen as needed
             (prn) use (i.e., <=12 hours per day) is not exclusionary.

          -  Sleep apnea: Subjects with clinically significant sleep apnea who require use of
             continuous positive airway pressure (CPAP) device or non-invasive positive pressure
             ventilation (NIPPV).

          -  Pulmonary rehabilitation: Subjects who have participated in the acute phase of a
             Pulmonary Rehabilitation Program within 4 weeks prior to Screening (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.

          -  Non-Compliance during Run-In Period: Failure to demonstrate adequate compliance
             defined as completion of Diary Card (completed all diary entries on at least 5 of the
             last 7 consecutive days), the ability to withhold anti-COPD medications and to keep
             clinic visit appointments. In addition, subjects must have recorded the Run-In study
             medication use on at least 5 of the last 7, consecutive days of the Run-In period to
             continue in the study.

          -  Potential of non-compliance: Subjects at risk of non-compliance, or unable to comply
             with the study procedures. Any infirmity, disability, or geographic location that
             would limit compliance for scheduled visits.

          -  Questionable validity of consent: Subjects with a history of psychiatric disease,
             intellectual deficiency, poor motivation or other conditions that will limit the
             validity of informed consent to participate in the study.

          -  Prior use of study medication/other investigational drugs: Subjects who have received
             an investigational drug within 30 days of entry into this study (Screening), or within
             5 drug half-lives of the investigational drug, whichever is longer. Note: Subjects who
             participated in a previously completed study and/or were excluded/ withdrawn from an
             ongoing study that included/includes FF/VI and/or VI are eligible to participate in
             the current study, if they have not received investigational study medication within
             30 days of Screening (Visit 1).

          -  Affiliation with investigator site: Study investigators, sub-investigators, study
             coordinators, employees of a participating investigator or immediate family members of
             the aforementioned are excluded from participating in this study.