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) (BEACON)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01529632
First received: February 6, 2012
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: QVA149
Drug: NVA237
Drug: QAB149
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Trough Forced Expiratory Volume in 1 Second (FEV1) After 28 Days of Blinded Treatment [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 1 [ Time Frame: 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose at Day 1 ] [ Designated as safety issue: No ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 28 [ Time Frame: 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose at Day 28 ] [ Designated as safety issue: No ]
    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.

  • Peak Forced Expiratory Volume in 1 Second (FEV1) on Days 1 and 28 Post-dose [ Time Frame: 5 min - 4 hr at Days 1 and 28 ] [ Designated as safety issue: No ]
    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.

  • Time Course of Forced Expiratory Volume in One Second (FEV1) (Pre-dose to 4 Hours Post Dose) on Day 28 [ Time Frame: -45 min, -15 min predose, 5 min, 30 min, 1 hr, 2hr, 3hr and 4 hr post-dose on Day 28 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in the Mean Daily, (Daytime and Nighttime Combined) Number of Puffs of Rescue Medication Used Over 28 Days of Treatment [ Time Frame: Baseline and 28 days ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Percentage of Days With 'no Daytime Symptoms' Over 28 Days of Treatment [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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.


Enrollment: 193
Study Start Date: May 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: QVA149
QVA149 plus placebo once daily for 28 days.
Drug: QVA149
QVA149 110/50 ug supplied as capsules in blister packs for inhalation via SDDPI, once daily
Drug: Placebo
Placebo capsules provided in blister packs for inhalation via SDDPI, once daily
Active Comparator: QAB149 + NVA237
Indacaterol maleate (QAB149) plus glycopyrronium bromide (NVA237) once daily for 28 days.
Drug: NVA237
NVA237 50 ug supplied as capsules in blister packs for inhalation via SDDPI, once daily
Drug: QAB149
QAB149 150 ug supplied as capsules in blister packs for inhalation via SDDPI , once daily

Detailed 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).

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 β2 agonists

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01529632

Locations
Austria
Novartis Investigative Site
Feldbach, Austria, 8330
Novartis Investigative Site
Grieskirchen, Austria, 4710
Novartis Investigative Site
Linz, Austria, 4020
Novartis Investigative Site
Wels, Austria, 4600
Denmark
Novartis Investigative Site
Aalborg, Denmark, DK-9100
Novartis Investigative Site
Copenhagen NV, Denmark, DK-2400
Novartis Investigative Site
Hvidovre, Denmark, DK-2650
Novartis Investigative Site
Odense C, Denmark, DK-5000
Novartis Investigative Site
Århus, Denmark, DK-8000
Netherlands
Novartis Investigative Site
Almelo, Netherlands, 7609 PP
Novartis Investigative Site
Eindhoven, Netherlands, 5623 EJ
Novartis Investigative Site
Harderwijk, Netherlands, 3840 AC
Novartis Investigative Site
Heerlen, Netherlands, 6419 PC
Novartis Investigative Site
Hengelo, Netherlands, 7555 DL
Novartis Investigative Site
Sittard-Geleen, Netherlands, 6162 BG
Novartis Investigative Site
Tubbergen, Netherlands, 7651 JH
Novartis Investigative Site
Veldhoven, Netherlands, 5504 DB
Norway
Novartis Investigative Site
Kløfta, Norway, 2040
Novartis Investigative Site
Kongsvinger, Norway, 2212
Novartis Investigative Site
Skedsmokorset, Norway, 2020
Novartis Investigative Site
Stavanger, Norway, 4005
Novartis Investigative Site
Trondheim, Norway, 7006
Sweden
Novartis Investigative Site
Göteborg, Sweden, 412 63
Novartis Investigative Site
Stockholm, Sweden, S-171 76
Novartis Investigative Site
Stockholm, Sweden, 111 57
Novartis Investigative Site
Uddevalla, Sweden, 451 50
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01529632     History of Changes
Other Study ID Numbers: CQVA149A2326, 2011-006050-91
Study First Received: February 6, 2012
Results First Received: December 2, 2013
Last Updated: January 16, 2014
Health Authority: United States: Food and Drug Administration
Austria: Agency for Health and Food Safety
Denmark: Danish Medicines Agency
Netherlands: Medicines Evaluation Board (MEB)
Norway: Norwegian Medicines Agency
Sweden: Medical Products Agency

Keywords provided by Novartis:
chronic obstructive pulmonary disease
COPD
QVA149
QAB149
NVA237
indacaterol
glycopyrronium bromide

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Glycopyrrolate
Adjuvants, Anesthesia
Central Nervous System Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014