A Multi-centre Randomized Double Blind 52-week Study to Assess the Safety of QVA149 Compared to QAB149 in Patients With COPD Who Have Moderate to Severe Airflow Limitation

Phase 3

Completed

• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Interventions: Drug: QVA149; Drug: QAB149; Drug: Placebo

• Registration Number: NCT01682863
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This study is to assess the safety and tolerability of two different doses of QVA149 and QAB149 in patients with moderate to severe airflow limitation.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-09-07
• Study First Submitted QC: 2012-09-07
• Study First Posted: 2012-09-11
• Study Start: 2012-10
• Primary Completion: 2014-06
• Study Completion: 2014-06
• Results First Submitted: 2015-06-22
• Status Verified: 2016-02
• Results First Submitted QC: 2016-02-29
• Last Update Submitted: 2016-02-29
• Results First Posted: 2016-03-30
• Last Update Posted: 2016-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 614

Inclusion Criteria

• Male and female adults aged ≥40 years
• Patients with stable COPD according to GOLD strategy (GOLD 2011).
• Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and <80% of the predicted normal, and a post-bronchodilator FEV1/FVC < 0.70.
• Current or ex-smokers who have a smoking history of at least 10 pack years.
• Patients with an mMRC ≥ grade 2

Exclusion Criteria

• History of long QT syndrome or prolonged QTc
• Patients who have had a COPD exacerbation that required treatment with antibiotics and/or systemic corticosteroids and/or hospitalization in the 6 weeks prior to Visit 1.
• Patients with Type I or uncontrolled Type II diabetes
• Patients with a history of asthma or have concomitant pulmonary disease
• Patients with paroxysmal (e.g. intermittent) atrial fibrillation. Only patients with persistent atrial fibrillation and controlled with a rate control strategy for at least six months could be eligible
• Patients who have clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of safety
• Other protocol defined inclusion/exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
QVA149 dose 1	QVA149	QVA149 27.5/12.5 μg capsules
QVA149 dose 2	QVA149	QVA149 27.5/25 μg capsules
QAB149	QAB149	QAB149 75 μg capsules
QAB149	Placebo	QAB149 75 μg capsules

Primary Outcome Measures

Name	Time	Method
Number of Patients With Adverse Events, Serious Adverse Events, and Death	56 weeks	The overall rate of adverse events reported from initiation through 30 days post last dose.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation	52 weeks	Percentage of participants experiencing moderate or severe Chronic Obstructive Pulmonary Disease (COPD)
Time to Premature Discontinuation of Treatment	56 weeks	methodTime to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment earl
Change From Baseline in Pre-dose Trough FEV1	Day 29, 57,, 85, 141, 197, 253, 309 and 365	Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction.
Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period	52 weeks	Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours.
Change From Baseline in 1 Hour Post-dose FEV1 Measurements	Day 1, 29, 57, 85, 141, 197, 253, 309, and 365	Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction.
Change From Baseline in FVC Measurement at All Post-baseline Time Points	Day1, 29, 57, 85, 141, 197, 253, 309, and 365	Pulmonary function assessments were performed using centralized spirometry according to international standards.
Change From Baseline in Mean Total Daily Symptom Scores	52 weeks	The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇪🇸 Valencia, Comunidad Valenciana, Spain