Assess Bronchodilator Effect QVM149 Dosed Either in the Morning or Evening Compared to Placebo in Patients With Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose); Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose); Treatment C: Placebo (morning dose) and placebo (evening dose)
Intervention description: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose); QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose); Placebo (morning dose) and placebo (evening dose)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This study is to assess the bronchodilator effects of QVM149 dosed once daily either in the morning or in the evening for 2 weeks compared to placebo. It will provide evidence of the comparability of lung function effects of QVM149 irrespective of the administration schedule
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: This is a double-blind masking.
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: QVM149,; asthma,; allergic asthma,; allergy triggered asthma,; reactive asthma,; asthma attack,; difficulty breathing

Summary:

      This was a randomized, placebo-controlled, double-blind, six-sequence, three-period
      cross-over study in asthma patients. The study consisted of a 14-day screening period,
      followed by a 14-day run-in period, and a treatment epoch which consists of three treatment
      periods, with a minimum duration of 14 days each followed (for the 2 first treatment periods)
      by a wash-out period. The duration of each treatment period may be extended up to a duration
      of 18 days if needed for operational reasons. The third treatment period was followed by a
      Study Completion evaluation at 1-7 days following the last dose. The treatment periods were
      separated by wash-out periods of 14 to 21 days duration.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients with a documented physician diagnosis of asthma and who additionally meet the
        following criteria:

          -  Patients receiving daily treatment with an inhaled corticosteroid at a low or medium
             daily dose

          -  On a stable regimen for at least 4 weeks prior to screening.

          -  Pre-bronchodilator FEV1 ≥ 60 % and < 100% of the predicted normal value for the
             patient during screening.

          -  Patients who demonstrate an increase in FEV1 of ≥ 12 % and ≥ 200 mL after
             administration of 400 μg salbutamol/360 μg albuterol (or equivalent dose) at
             Screening. All patients must perform a reversibility test at Screening.

          -  At screening, and baseline (day 1 pre-dose time) of the first treatment period, vital
             signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the
             sitting position and again in the standing position as outlined in the SOM. Sitting
             and standing vital signs should be within the following ranges:

          -  oral body temperature between 35.0-37.5 °C

          -  systolic blood pressure, 90-159 mmHg

          -  diastolic blood pressure, 50-99 mmHg

          -  pulse rate, 40-90 bpm

          -  Hypertensive patients must have been on stable antihypertensive therapy for at least 4
             weeks prior to screening to be included in the trial.

          -  Patients must weigh at least 50 kg at screening to participate in the study, and must
             have a body mass index (BMI) within the range of 18 to 40 kg/m2.

        Exclusion Criteria:

          -  Contraindicated for treatment with, or having a history of reactions/ hypersensitivity
             to any of the drugs of a similar class

          -  Patients who have had an asthma attack/exacerbation requiring systemic steroids or
             hospitalization or emergency room visit within 1 year of Screening.

          -  Patients who have had previous intubation for a severe asthma ttack/exacerbation.

          -  Patients with a history of clinically relevant bronchoconstriction upon repeated
             forced expiratory maneuvers.

          -  History of paradoxical bronchospasm in response to inhaled medicines.

          -  Patients who during the run-in period prior to randomization require the use of ≥12
             puffs / 24 hours of rescue medication for 48 hours (over two consecutive days) or who
             have a decline in PEF from the reference PEFof ≥ 30% for 6 consecutive scheduled PEF
             readings

          -  Patients who do not maintain regular day/night, waking/sleeping cycles (e.g., night
             shift workers).