Assess Bronchodilator Effect QVM149 Dosed Either in the Morning or Evening Compared to Placebo in Patients With Asthma (QVM149)

• ClinicalTrials.gov Identifier: NCT03108027
• Recruitment Status: Completed
• First Posted: April 11, 2017
• Results First Posted: May 21, 2019
• Last Update Posted: January 5, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: March 23, 2017
• First Posted Date: April 11, 2017
• Results First Submitted Date: February 22, 2019
• Results First Posted Date: May 21, 2019
• Last Update Posted Date: January 5, 2021
• Actual Study Start Date: June 26, 2017
• Actual Primary Completion Date: February 24, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 20, 2019)

FEV1 Standardized Area Under the Curve (AUC 0-24h) After Last Evening Dose of 14-day Treatment Period [ Time Frame: At the end of each treatment period day 14 pre-dose to 24 hours post-dose. ]

Weighted mean forced expiratory volume in 1 second (FEV1) over 24 h (AUC0-24h) following 14 days of treatment with QVM149 dosed in the morning, QVM149 dosed in the evening and placebo.

Original Primary Outcome Measures (submitted: April 4, 2017)

FEV1 over 24h [ Time Frame: At the end of each treatment period day 14 pre-dose to 24 hours post-dose. ]

Weighted mean forced expiratory volume in 1 second (FEV1) over 24 h (AUC0-24h) following 14 days of treatment with QVM149 dosed in the morning, QVM149 dosed in the evening and placebo.

Current Secondary Outcome Measures (submitted: May 20, 2019)

• Trough FEV1 After 24h [ Time Frame: At the end of each treatment period day 14 pre-dose to 24 hours post-dose. ]
  FEV1 at approximately 24 h after the last p.m. or penultimate a.m. dose. Morning and evening trough FEV1 (L) were analyzed by time of day. For morning trough FEV1 (L) assessments this meant that the spirometric assessment was done approximately 24 h after last morning dose and approximately 12 h after last evening dose.
• Peak Expiratory Flow (PEF) [ Time Frame: From treatment period start through study completion (up to 19 weeks). ]
  Peak expiratory flow (PEF) is the maximum flow generated during a forceful exhalation, starting from full lung inflationDaily morning and evening peak expiratory flow rate from Day 2 to Day14 during the three treatment periods.

Original Secondary Outcome Measures (submitted: April 4, 2017)

• FEV1 after 24h [ Time Frame: At the end of each treatment period day 14 pre-dose to 24 hours post-dose. ]
  FEV1 at approximately 24 h after the last p.m. or penultimate a.m. dose.
• Peak expiratory flow [ Time Frame: From treatment period start through study completion (up to 19 weeks). ]
  Daily morning and evening peak expiratory flow rate from Day 2 to Day14 during the three treatment periods.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Assess Bronchodilator Effect QVM149 Dosed Either in the Morning or Evening Compared to Placebo in Patients With Asthma
• Official Title: A Randomized, Double-blind, Repeat Dose Cross-over Study to Assess the Bronchodilator Effects of Once Daily QVM149 Following Morning or Evening Dosing for 14 Days Compared to Placebo in Patients With Asthma
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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.

Primary Purpose: Treatment

• Condition: Asthma

Intervention

• Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)
  Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)
• Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)
  QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)
• Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)
  Placebo (morning dose) and placebo (evening dose)

Study Arms

• Experimental: Sequence 1
  Patients will receive in a sequential order the following interventional treatments: A,B and C.
  Interventions:

  • Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)
  • Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)
  • Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)
• Experimental: Sequence 2
  Patients will receive in a sequential order the following interventional treatments: B, A and C.
  Interventions:

  • Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)
  • Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)
  • Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)
• Experimental: Sequence 3
  Patients will receive in a sequential order the following interventional treatments: C, B and A.
  Interventions:

  • Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)
  • Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)
  • Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)
• Experimental: Sequence 4
  Patients will receive in a sequential order the following interventional treatments : C, A and B.
  Interventions:

  • Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)
  • Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)
  • Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)
• Experimental: Sequence 5
  Patients will receive in a sequential order the following interventional treatments: A, C and B.
  Interventions:

  • Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)
  • Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)
  • Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)
• Experimental: Sequence 6
  Patients will receive in a sequential order the following interventional treatments: B, C and A.
  Interventions:

  • Drug: Treatment A: Matching placebo (morning dose) and QVM149 150/50/80 μg (evening dose)
  • Drug: Treatment B: QVM149 150/50/80 μg (morning dose) and matching placebo (evening dose)
  • Drug: Treatment C: Placebo (morning dose) and placebo (evening dose)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 6, 2018): 38
• Original Estimated Enrollment (submitted: April 4, 2017): 36
• Actual Study Completion Date: February 24, 2018
• Actual Primary Completion Date: February 24, 2018 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Netherlands, United Kingdom

Administrative Information

• NCT Number: NCT03108027
• Other Study ID Numbers: CQVM149B2209; 2017-000644-17 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: May 2019