A 12 Week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol Maleate / Glycopyrronium Bromide in COPD Patients With Moderate to Severe Airflow Limitation.

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

Official title:

A 12-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol Maleate / Glycopyrronium Bromide in COPD Patients With Moderate to Severe Airflow Limitation.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01727141
• Other study ID #: CQVA149A2336
• Status: Completed
• Phase: Phase 3
• First received: November 12, 2012
• Last updated: July 13, 2015
• Start date: November 2012
• Est. completion date: February 2014

Study information

• Verified date: July 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will assess the efficacy, safety and tolerability of QVA149 in patients with moderate to severe airflow limitation.

Description:

NOTE: Detailed Description: data not entered

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1042
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Male and female patients that have signed informed consent and are >/= 40 years of age.

• Patients with stable COPD according to GOLD 2011.

• Patients with a post-bronchodilator FEV1 of >/= 30% and < 80% predicted 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 or greater.

Exclusion Criteria:

• Patients with Type I or uncontrolled Type II diabetes - Patients with a history of long QT syndrome or whose QTc measured at Visit 101 (Fridericia method) is prolonged (>450 ms for males and females) and confirmed by a central assessor. (These patients should not be re-screened.)

• Patients who have a clinically significant ECG abnormality at Visit 101 or Visit 102. (These patients should not be re-screened.)

• Patients with a history of malignancy of any organ system, treated or untreated, within the last five years.

• Patients with narrow-angle glaucoma, BPH or bladder-neck obstruction or moderate-severe renal impairment or urinary retention.

• Patients who had a COPD exacerbation within 6 weeks prior to screening.

• Patients who have a respiratory tract infection within 4 weeks prior to screening.

• Patients requiring long term oxygen therapy prescribed for more than 12 hr per day.

• Patients with a history of asthma. 8. Patients with an onset of respiratory symptoms, including COPD diagnosis, prior to age 40 years.

• Patients with a blood eosinophil count of greater than 600 mm/3 during run-in.

• Patients with concomitant pulmonary disease.

• Patients with a diagnosis of alpha-1 anti-trypsin deficiency.

• Patients with active pulmonary tuberculosis.

• Patients in the active phase of a pulmonary rehabilitation programme.

• 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 (COPD)
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• QVA149
QVA149 was supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI
• QAB149
QAB149 was supplied in capsule form in blister packs for use in the Novartis Concept1 SDDPI.
• NVA237
NVA237 was supplied in capsule form in blister packs for use in the Novartis Concept1 SDDPI.
• Placebo
Placebo was supplied in capsule form in blister packs for use in the Novartis Concept1 SDDPI.

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Burlington	Ontario
Canada	Novartis Investigative Site	Courtice	Ontario
Canada	Novartis Investigative Site	Gatineau	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Pointe-Claire	Quebec
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Québec	Quebec
Canada	Novartis Investigative Site	Sainte-Foy	Quebec
Canada	Novartis Investigative Site	Sainte-Foy	Quebec
Canada	Novartis Investigative Site	Sherbrooke	Quebec
Canada	Novartis Investigative Site	St-Charles-Borromée	Quebec
Canada	Novartis Investigative Site	St-Romuald	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Trois-Rivières	Quebec
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Victoriaville	Quebec
Canada	Novartis Investigative Site	Windsor	Ontario
Philippines	Novartis Investigative Site	Bulacan
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Quezon City
Philippines	Novartis Investigative Site	San Pablo City, Laguna
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Tarnow
Poland	Novartis Investigative Site	Wroclaw
Romania	Novartis Investigative Site	Arad
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucharest	District 1
Romania	Novartis Investigative Site	Bucharest	District 1
Romania	Novartis Investigative Site	Bucharest	District 3
Romania	Novartis Investigative Site	Bucharest	District 3
Romania	Novartis Investigative Site	Craiova	Dolj
Romania	Novartis Investigative Site	Deva
Romania	Novartis Investigative Site	Iasi	Jud. Iasi
Spain	Novartis Investigative Site	Baracaldo	Vizcaya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Caceres	Extremadura
Spain	Novartis Investigative Site	Gijon	Asturias
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Mérida	Extremadura
Spain	Novartis Investigative Site	Palma De Mallorca	Islas Baleares
Spain	Novartis Investigative Site	Ponferrada	Castilla y Leon
Spain	Novartis Investigative Site	Salt	Cataluña
Spain	Novartis Investigative Site	Sant Boi de Llobregat	Cataluña
Spain	Novartis Investigative Site	Santander	Cantabria
Spain	Novartis Investigative Site	Valladolid	Castilla y Leon
Ukraine	Novartis Investigative Site	Dnipropetrovsk
Ukraine	Novartis Investigative Site	Dnipropetrovsk
Ukraine	Novartis Investigative Site	Donetsk
Ukraine	Novartis Investigative Site	Kharkiv
Ukraine	Novartis Investigative Site	Kharkiv
Ukraine	Novartis Investigative Site	Kharkiv
Ukraine	Novartis Investigative Site	Kiev
Ukraine	Novartis Investigative Site	Kiev
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Luhansk
Ukraine	Novartis Investigative Site	Lviv
Ukraine	Novartis Investigative Site	Poltava
Ukraine	Novartis Investigative Site	Vinnytsia
Ukraine	Novartis Investigative Site	Vinnytsia
Ukraine	Novartis Investigative Site	Zaporizhzhya
Ukraine	Novartis Investigative Site	Zaporizhzhya
Ukraine	Novartis Investigative Site	Zhytomyr
United States	Novartis Investigative Site	Anderson	South Carolina
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Biloxi	Mississippi
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boerne	Texas
United States	Novartis Investigative Site	Brooklyn	New York
United States	Novartis Investigative Site	Brooklyn	New York
United States	Novartis Investigative Site	Chattanooga	Tennessee
United States	Novartis Investigative Site	Chiefland	Florida
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Clearwater	Florida
United States	Novartis Investigative Site	Columbia	Maryland
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dublin	Ohio
United States	Novartis Investigative Site	Edina	Minnesota
United States	Novartis Investigative Site	El Paso	Texas
United States	Novartis Investigative Site	Fountain Valley	California
United States	Novartis Investigative Site	Fridley	Minnesota
United States	Novartis Investigative Site	Fullerton	California
United States	Novartis Investigative Site	Great Neck	New York
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Hendersonville	North Carolina
United States	Novartis Investigative Site	Huntington Beach	California
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Lynn Haven	Florida
United States	Novartis Investigative Site	Marion	Ohio
United States	Novartis Investigative Site	Medford	Oregon
United States	Novartis Investigative Site	Meridian	Idaho
United States	Novartis Investigative Site	Mesa	Arizona
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Montclair	California
United States	Novartis Investigative Site	Montgomery	Alabama
United States	Novartis Investigative Site	Newport News	Virginia
United States	Novartis Investigative Site	O'Fallon	Illinois
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Orange	California
United States	Novartis Investigative Site	Orangevale	California
United States	Novartis Investigative Site	Papillion	Nebraska
United States	Novartis Investigative Site	Paramount	California
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	River Forest	Illinois
United States	Novartis Investigative Site	Riverside	California
United States	Novartis Investigative Site	Rochester	Minnesota
United States	Novartis Investigative Site	Roseville	California
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	Savannah	Georgia
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	South Burlington	Vermont
United States	Novartis Investigative Site	Spartanburg	South Carolina
United States	Novartis Investigative Site	St. Charles	Missouri
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	Tacoma	Washington
United States	Novartis Investigative Site	Tipton	Pennsylvania
United States	Novartis Investigative Site	Torrance	California
United States	Novartis Investigative Site	Union	South Carolina
United States	Novartis Investigative Site	Waltham	Massachusetts
United States	Novartis Investigative Site	Waterbury	Connecticut
United States	Novartis Investigative Site	Wheat Ridge	Colorado
Vietnam	Novartis Investigative Site	Hanoi
Vietnam	Novartis Investigative Site	Ho Chi Minh
Vietnam	Novartis Investigative Site	Ho Chi Minh City

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Canada,  Philippines,  Poland,  Romania,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) (0-12 Hours (h))	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. Missing values of FEV1 AUC0-12 at Day 1 and Week 12 will not imputed. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time.	baseline (BL), 12 Weeks	No
Secondary	Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score	Participants reported change in health status by using the SGRQ. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that cause or are limited by breathlessness; Part II is also concerned with "Impacts", which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A score was calculated for each of these 3 subscales and a "Total" score was calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. Missing week 12 data were imputed with Last Observation Carried Forward (LOCF) method but only if measured at day >= 29. A negative change from baseline indicates improvement.	BL, 12 Weeks	No
Secondary	Percentage of Participants With a Clinically Important Improvement of at Least 4 Units in the SGRQ Total Score	Participants reported change in health status by using the SGRQ. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that cause or are limited by breathlessness; Part II is also concerned with "Impacts", which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A score was calculated for each of these 3 subscales and a "Total" score was calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.	12 weeks	No
Secondary	Change From Baseline in Trough FEV1	Pulmonary function assessments were performed using centralized spirometry according to international standards. Trough FEV1 was analyzed using the same MMRM as specified for FEV1. Trough FEV1 was defined as the mean of FEV1 at 23 h 15 min and 23 h 45 min after the morning dose of the previous day. Before the mean was calculated, a time window of 10 - 13 hours post-evening dose was applied to these 2 measurements. Recordings outside the time window were set to missing.	BL, day 2, day 86	No
Secondary	Change From Baseline in Pre-dose Trough FEV1	Pulmonary function assessments were performed using centralized spirometry according to international standards. Pre-dose trough FEV1 was analyzed using the same MMRM as specified for FEV1. Pre-dose trough FEV1 was defined as the mean of FEV1 at -45 min and -15 min before the morning dose. Since the time of evening dose of the previous day was not recorded at these visits, no time window was applied.	BL, day 85	No
Secondary	Change From Baseline in FEV1	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.	BL, Day 1:5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h55 min;Day 2: 23h15min, 23h45min;Day 15: -45min, -15min, 1h;Day 29: -45 min, -15min, 1h;Day 57: -45min, -15min, 1h;Day 85: -45min, -15min, 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h55min;Day 86: 23h15min; 23h45min	No
Secondary	Change From Baseline in FVC	Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC 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 FVC measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.	BL, Day 1: 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h55 min;Day 2: 23h15min, 23h45min;Day 15: -45min, -15min, 1h;Day 29: -45 min, -15min, 1h;Day 57: -45min, -15min, 1h;Day 85: -45min, -15min, 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h 55min;Day 86: 23h15min; 23h45min	No
Secondary	Change From Baseline in Standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)	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. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time.	BL, day 1, week 12	No
Secondary	Transitional Dyspnea Index (TDI) Focal Score	The Baseline Dyspnea Index (BDI) / TDI is an instrument used to assess a participant's level of dyspnea. The BDI and TDI each have three domains: functional impairment, magnitude of task and magnitude of effort. BDI domains were rated from 0 (severe) to 4 (unimpaired) and rates summed for baseline focal score ranged from 0 to 12; lower scores mean worse severity. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of =1 was defined as a clinically important improvement from baseline.	BL, 12 weeks	No
Secondary	Change From Baseline in Mean Daily Number of Puffs of Rescue Medication	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. A negative change from baseline indicates improvement.	BL, 12 Weeks	No
Secondary	Change From Baseline in Mean Total Daily Symptom Score, Mean Daytime Total Symptom Score and Mean Nighttime Total Symptom Score	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.	BL, 12 Weeks	No