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

Asthma Clinical Trial

— QVM149  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03108027
• Other study ID #: CQVM149B2209
• Secondary ID: 2017-000644-17
• Status: Completed
• Phase: Phase 2
• Start date: June 26, 2017
• Est. completion date: February 24, 2018

Study information

• Verified date: May 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: February 24, 2018
• Est. primary completion date: February 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• 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)
• 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)
• Treatment C: Placebo (morning dose) and placebo (evening dose)
Placebo (morning dose) and placebo (evening dose)

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Frankfurt Am Main Hessen
Germany	Novartis Investigative Site	Grosshansdorf
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Wiesbaden
Netherlands	Novartis Investigative Site	Groningen	GZ
United Kingdom	Novartis Investigative Site	Machester

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FEV1 Standardized Area Under the Curve (AUC 0-24h) After Last Evening Dose of 14-day Treatment Period	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.	At the end of each treatment period day 14 pre-dose to 24 hours post-dose.
Secondary	Trough FEV1 After 24h	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.	At the end of each treatment period day 14 pre-dose to 24 hours post-dose.
Secondary	Peak Expiratory Flow (PEF)	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.	From treatment period start through study completion (up to 19 weeks).

External Links

•   A Plain Language Trial Summary is available on novartisclinicatrials.com