Comparison of Safety and Efficacy of the Combination Product QVA149A Against the Concurrent Administration of the Individual Components, QAB149 and NVA237, in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease Clinical Trial

— BEACON  

Official title:

A Study to Compare the Efficacy and Safety of Once Daily QVA149 Versus the Once Daily Concurrent Administration of QAB149 Plus NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01529632
• Other study ID #: CQVA149A2326
• Secondary ID: 2011-006050-91
• Status: Completed
• Phase: Phase 3
• First received: February 6, 2012
• Last updated: January 16, 2014
• Start date: May 2012
• Est. completion date: December 2012

Study information

• Verified date: January 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustria: Agency for Health and Food SafetyDenmark: Danish Medicines AgencyNetherlands: Medicines Evaluation Board (MEB)Norway: Norwegian Medicines AgencySweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

The study assessed the safety and efficacy of the fixed combination product QVA149 versus the component products QAB149 and NVA237, administered concurrently, in patients that have moderate to severe chronic obstructive pulmonary disease (COPD).

Description:

The study assessed the safety and efficacy of the fixed combination product QVA149 versus the component products QAB149 and NVA237, administered concurrently, in patients that have moderate to severe chronic obstructive pulmonary disease (COPD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 193
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Male or female adults aged = 40 yrs

• Smoking history of at least 10 pack years

• Diagnosis of COPD (moderate to severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2010)

• Post-bronchodilator FEV1 < 80% and = 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) < 70%

Exclusion Criteria:

• Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1

• Patients with concomitant pulmonary disease

• Patients with a history of asthma

• Any patient with lung cancer or a history of lung cancer

• Patients with a history of certain cardiovascular co-morbid conditions

• Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency

• Patients in the active phase of a supervised pulmonary rehabilitation program

• Patients contraindicated for inhaled anticholinergic agents and ß2 agonists

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• QVA149
QVA149 110/50 ug supplied as capsules in blister packs for inhalation via SDDPI, once daily
• NVA237
NVA237 50 ug supplied as capsules in blister packs for inhalation via SDDPI, once daily
• QAB149
QAB149 150 ug supplied as capsules in blister packs for inhalation via SDDPI , once daily
• Placebo
Placebo capsules provided in blister packs for inhalation via SDDPI, once daily

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Feldbach
Austria	Novartis Investigative Site	Grieskirchen
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Wels
Denmark	Novartis Investigative Site	Aalborg
Denmark	Novartis Investigative Site	Århus
Denmark	Novartis Investigative Site	Copenhagen NV
Denmark	Novartis Investigative Site	Hvidovre
Denmark	Novartis Investigative Site	Odense C
Netherlands	Novartis Investigative Site	Almelo
Netherlands	Novartis Investigative Site	Eindhoven
Netherlands	Novartis Investigative Site	Harderwijk
Netherlands	Novartis Investigative Site	Heerlen
Netherlands	Novartis Investigative Site	Hengelo
Netherlands	Novartis Investigative Site	Sittard-Geleen
Netherlands	Novartis Investigative Site	Tubbergen
Netherlands	Novartis Investigative Site	Veldhoven
Norway	Novartis Investigative Site	Kløfta
Norway	Novartis Investigative Site	Kongsvinger
Norway	Novartis Investigative Site	Skedsmokorset
Norway	Novartis Investigative Site	Stavanger
Norway	Novartis Investigative Site	Trondheim
Sweden	Novartis Investigative Site	Göteborg
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Uddevalla

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Austria,  Denmark,  Netherlands,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough Forced Expiratory Volume in 1 Second (FEV1) After 28 Days of Blinded Treatment	Spirometry was conducted according to internationally accepted standards. Trough FEV1 is defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings measured at day 29, after 28 days of treatment. Mixed model: Trough FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.	Day 29	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 1	Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.	0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose at Day 1	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 28	Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 28 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.	0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose at Day 28	No
Secondary	Peak Forced Expiratory Volume in 1 Second (FEV1) on Days 1 and 28 Post-dose	Spirometry was conducted according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded in the period between 5 minutes and 4 hours post dose. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate.	5 min - 4 hr at Days 1 and 28	No
Secondary	Time Course of Forced Expiratory Volume in One Second (FEV1) (Pre-dose to 4 Hours Post Dose) on Day 28	Time course of Forced Expiratory Volume in 1 second (FEV1) was measured at -45 min, -15 min predose, 5 min, 30 min, 1 hr, 2hr, 3hr and 4 hr post-dose on Day 28. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.	-45 min, -15 min predose, 5 min, 30 min, 1 hr, 2hr, 3hr and 4 hr post-dose on Day 28	No
Secondary	Change From Baseline in the Mean Daily, (Daytime and Nighttime Combined) Number of Puffs of Rescue Medication Used Over 28 Days of Treatment	The number of puffs of rescue medication taken in the previous 12 hours was recorded in the Patient Diary in the morning and evening. The total number of puffs of rescue medication per day over the whole active treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening) then a half day was used in the denominator.	Baseline and 28 days	No
Secondary	Change From Baseline in Percentage of Days With 'no Daytime Symptoms' Over 28 Days of Treatment	The mean total symptom scores and mean individual symptom scores for the patient were calculated for the whole study period. The mean change from baseline in the total scores and in the individual scores were summarized by treatment and were analyzed for the percentage of 'nights with no nighttime awakenings'. The symptom variables for the whole active treatment period was analyzed using the similar MIXED model as for the primary endpoint, with the baseline FEV1 term being replaced by the respective baseline symptom variables.	28 days	No