Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium
Condition: Asthma
MeSH terms: Asthma
Intervention: QVM149; Salmeterol/fluticasone plus tiotropium
Intervention description: Indacaterol acetate / glycopyrronium bromide / mometasone furoate; Free triple arm of salmeterol / fluticasone plus tiotropium
Intervention MeSH terms: Fluticasone; Tiotropium Bromide; Salmeterol Xinafoate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking description: The free triple combination of salmeterol/fluticasone + tiotropium was open label, for which investigators and patients had full knowledge that the patient had been assigned free triple combination comparator treatment. Within the two QVM149 treatment arms patients, investigator staff, and persons performing the assessments, remained blind to the identity of the actual QVM149 treatment dose but had full knowledge that the patient had been assigned QVM149 as study treatment. The data analysts and sponsor team were blinded to Case Report Forms that reveal the treatment arm. Randomization data and treatment codes were kept strictly confidential until the time of unblinding, and was not accessible by anyone else involved in the study.
Enrollment: 1426.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: QVM149; Asthma; Moderate Asthma; Severe Asthma; ICS/LABA/LAMA; ICS/LABA; LAMA; Adult

Summary:

      The purpose of this trial was to demonstrate that the efficacy of two treatment arms of the
      fixed-dose combination product QVM149 was non-inferior to the efficacy of the free
      combination arm of salmeterol/ fluticasone+ tiotropium in uncontrolled moderate to severe
      asthmatic patients.

      The planned duration of treatment in this study was 24 weeks, followed up by a 7-day
      follow-up period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with a diagnosis of asthma for a period of at least 6 months prior to Visit 1
             with current asthma severity ≥ step 4 (GINA 2017).

          -  Patients who had used ICS/LABA combinations for asthma for at least 3 months and at
             stable medium or high dose of ICS/LABA for at least 1 month prior to Visit 1.

          -  Patients were required to be symptomatic at screening despite treatment with medium or
             high stable doses of ICS/LABA as defined by ACQ-7 score ≥ 1.5 at visits 101 and 201
             (randomization visit).

          -  Patients with history of at least one severe asthma exacerbation which required
             medical care from a physician, emergency room visit (or local equivalent structure) or
             hospitalization in the 12 months prior to Visit 1 and required systemic corticosteroid
             treatment for at least 3 days including physician guided self-management treatment
             with oral corticosteroids as part of written asthma action plan.

          -  Pre-bronchodilator FEV1 of < 85 % of the predicted normal value for the patient after
             withholding bronchodilators prior to spirometry at both Visit 101 and Visit 201.

          -  Patients who demonstrated an increase in FEV1 of ≥ 12% and 200 ml.

        Exclusion Criteria:

          -  Patients who had a smoking history of greater than 20 pack years.

          -  Patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD).

          -  Patients who had an asthma attack/exacerbation requiring systemic steroids or
             hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening).

          -  Patients treated with a LAMA for asthma within 3 months prior to Visit 1.

          -  Patients who had a respiratory tract infection or clinical significant asthma
             worsening as defined by Investigator within 4 weeks prior to Visit 1 or between Visit
             1 and Visit 201.