Clinical trial NCT01712516: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: COPD, QVA149
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-10-23
Enrollment: 1001
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the efficacy, safety and tolerability of indacaterol maleate/glycopyrronium bromide in patients with moderate to severe airflow limitation.


Eligibility criteria: 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

Primary outcomes:
measure: Primary: Change From Baseline in Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) (0-12 Hours (h))
timeFrame: baseline (BL), 12 weeks
Secondary outcomes:
measure: Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score
timeFrame: BL, 12 Weeks
measure: Percentage of Participants With a Clinically Important Improvement of at Least 4 Units in the SGRQ Total Score
timeFrame: 12 weeks
measure: Change From Baseline in Trough FEV1
timeFrame: BL, day 2, day 86
measure: Change From Baseline in Pre-dose Trough FEV1
timeFrame: BL, day 85
measure: Change From Baseline in FEV1
timeFrame: 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; day 86: 23h15min; 23h45min
measure: Change From Baseline in FVC
timeFrame: 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; day 86: 23h15min; 23h45min
measure: 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)
timeFrame: BL, day 1, 12 weeks
measure: Transitional Dyspnea Index (TDI) Focal Score
timeFrame: BL, 12 weeks
measure: Secondary: Change From Baseline in Mean Daily Number of Puffs of Rescue Medication
timeFrame: BL, 12 weeks
measure: Secondary: Change From Baseline in Mean Total Daily Symptom Score, Mean Daytime Total Symptom Score and Mean Nighttime Total Symptom Score
timeFrame: BL, 12 weeks
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Novartis Investigative Site
state: Alabama
city: *See Various Dept.'s*
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facility: Novartis Investigative Site
state: Arizona
city: Tempe
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city: Buena Park
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state: California
city: Fullerton
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state: California
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facility: Novartis Investigative Site
state: California
city: Riverside
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facility: Novartis Investigative Site
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facility: Novartis Investigative Site
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state: Florida
city: Clearwater
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facility: Novartis Investigative Site
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city: Miami
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city: Orlando
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state: Georgia
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state: Louisiana
city: Henderson
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city: Las Vegas
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city: Shelby
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facility: Novartis Investigative Site
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facility: Novartis Investigative Site
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city: Dallas
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state: Atlantico
city: Armenia
country: Colombia
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city: Barranquilla
country: Colombia
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city: Alexandria
country: Egypt
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city: Beuvry
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country: Guatemala
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city: Guatemala City
country: Guatemala
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country: Guatemala
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country: Hungary
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city: Debrecen
country: Hungary
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city: Deszk
country: Hungary
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city: Godollo
country: Hungary
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city: Gyor
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city: Szazhalombatta
country: Hungary
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city: Szombathely
country: Hungary
facility: Novartis Investigative Site
city: Tatabanya
country: Hungary
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city: Panama City
country: Panama
facility: Novartis Investigative Site
state: Panamá
city: Bardejov
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Bojnice
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Humenne
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Liptovsky Hradok
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Nitra
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Vrable
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Galanta
country: Slovakia
facility: Novartis Investigative Site
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Kralovsky Chlmec
country: Slovakia
facility: Novartis Investigative Site
city: Martin
country: Slovakia
facility: Novartis Investigative Site
city: Presov
country: Slovakia
facility: Novartis Investigative Site
city: Prievidza
country: Slovakia
facility: Novartis Investigative Site
city: Spisská Nová Ves
country: Slovakia
facility: Novartis Investigative Site
city: Zvolen
country: Slovakia
facility: Novartis Investigative Site
city: Golnik
country: Slovenia
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Mahler DA, Kerwin E, Murray L, Dembek C. The Impact of Twice-Daily Indacaterol/Glycopyrrolate on the Components of Health-Related Quality of Life and Dyspnea in Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease. Chronic Obstr Pulm Dis. 2019 Oct 23;6(4):308-20. doi: 10.15326/jcopdf.6.4.2019.0131.