Efficacy and Safety of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) Using Salmeterol as Active Control

A 26-week Treatment, Multi-center, Randomized, Double-blind, Double- Dummy, Placebo-controlled, Parallel-group Study to Assess the Efficacy, and Safety of Indacaterol (150 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease, Using Salmeterol (50 µg b.i.d.) as an Active Control

This study evaluated the safety and efficacy of 26 weeks treatment with indacaterol, placebo or salmeterol in patients with chronic obstructive pulmonary disease.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Indacaterol 150 μg; Drug: Placebo to Salmeterol; Drug: Placebo to Indacaterol; Drug: Salmeterol 50 μg

• Study Type: Interventional
• Enrollment (Actual): 1002
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Edmonton, Canada
    • Novartis Investigative Site
  • Edmonton, Canada
    • Novartis Investigator Site
  • London, Canada
    • Novartis Investigator Site
  • Mirabel, Canada
    • Novartis Investigator Site
  • Montreal, Canada
    • Novartis Investigator Site
  • Toronto, Canada
    • Novartis Investigator Site
• Colombia
  • Barranquilla, Colombia
    • Novartis Investigator Site
  • Bogota D.C., Colombia
    • Novartis Investigator Site
  • Medellin, Colombia
    • Novartis Investigator Site
• Czech Republic
  • Cvikov, Czech Republic
    • Novartis Investigator Site
  • Lovosice, Czech Republic
    • Novartis Investigator Site
  • Novy Jocin, Czech Republic
    • Novartis Investigator Site
  • Pardubice, Czech Republic
    • Novartis Investigator Site
  • Praha, Czech Republic
    • Novartis Investigator Site
  • Zatec, Czech Republic
    • Novartis Investigative Site
• Denmark
  • Aalborg, Denmark
    • Novartis Investigator Site
  • Arhus, Denmark
    • Novartis Investigator Site
  • Copenhagen, Denmark
    • Novartis Investigative Site
  • Copenhagen, Denmark
    • Novartis Investigator Site
  • Frederikssund, Denmark
    • Novartis Investigator Site
  • Hellerup, Denmark
    • Novartis Investigator Site
  • Hvidovre, Denmark
    • Novartis Investigator Site
  • Odense, Denmark
    • Novartis Investigator Site
  • Roslev, Denmark
    • Novartis Investigator Site
  • Silkeborg, Denmark
    • Novartis Investigative Site
  • Soborg, Denmark
    • Novartis Investgative Site
  • Vaerloese, Denmark
    • Novartis Investigator Site
• Finland
  • Hus, Finland
    • Novartis Investigator Site
  • Jyvaskyla, Finland
    • Novartis Investigator Site
  • Lahti, Finland
    • Novartis Investigator Site
  • Oulu, Finland
    • Novartis Investigator Site
  • Tampere, Finland
    • Novartis Investigator Site
  • Turku, Finland
    • Novartis Investigator Site
• France
  • Ambroise, France
    • Novartis Investigative Site
  • Beuvry, France
    • Novartis Investigative Site
  • Ferolles-Attilly, France
    • Novartis Investgative Site
  • Nice, France
    • Novartis Investigator Site
• Germany
  • Bad Segeberg, Germany
    • Novartis Investigator Site
  • Berlin, Germany
    • Novartis Investigator Site
  • Bielefeld, Germany
    • Novartis Investigator Site
  • Bochum, Germany
    • Novartis Investigator Site
  • Bonn, Germany
    • Novartis Investigator Site
  • Bruehl, Germany
    • Novartis Investigator Site
  • Cottbus, Germany
    • Novartis Investigator Site
  • Dortmund, Germany
    • Novartis Investigator Site
  • Dueren, Germany
    • Novartis Investigator Site
  • Eggenfelden, Germany
    • Novartis Investigator Site
  • Eschwege, Germany
    • Novartis Investigator Site
  • Forchheim, Germany
    • Novartis Investigator Site
  • Freudenberg, Germany
    • Novartis Investigator Site
  • Furth, Germany
    • Novartis Investigator Site
  • Gelsenkirchen, Germany
    • Novartis Investigator Site
  • Gummersbach, Germany
    • Novartis Investigator Site
  • Hagen, Germany
    • Novartis Investigator Site
  • Hannover, Germany
    • Novartis Investigator Site
  • Kassel, Germany
    • Novartis Investigator Site
  • Kempten, Germany
    • Novartis Investigator Site
  • Koeln, Germany
    • Novartis Investigator Site
  • Landsberg am Lech, Germany
    • Novartis Investigator Site
  • Langenfeld, Germany
    • Novartis Investigator Site
  • Leipzig, Germany
    • Novartis Investigator Site
  • Mainz, Germany
    • Novartis Investigator Site
  • Muenchen, Germany
    • Novartis Investigator Site
  • Munich, Germany
    • Novartis Investigator Site
  • Neuss, Germany
    • Novartis Investigator Site
  • Nuremburg, Germany
    • Novartis Investigator Site
  • Oschersleben, Germany
    • Novartis Investigator Site
  • Ruhmannsfelden, Germany
    • Novartis Investigator Site
  • Sinsheim, Germany
    • Novartis Investigator Site
  • Solingen, Germany
    • Novartis Investigator Site
  • Steinfort-borghorst, Germany
    • Novartis Investigator Site
  • Vilshofen, Germany
    • Novartis Investigator Site
  • Wallerfing, Germany
    • Novartis Investigator Site
  • Witten, Germany
    • Novartis Investigator Site
• Hungary
  • Budapest, Hungary
    • Novartis Investigator Site
  • Debrechen, Hungary
    • Novartis Investigator Site
  • Deszk, Hungary
    • Novartis Investigator Site
  • Mosonmagyarovar, Hungary
    • Novartis Investigator Site
  • Szekesfehervar, Hungary
    • Novartis Investigator Site
• Iceland
  • Reykhavik, Iceland
    • Novartis Investigator Site
• India
  • Chennai, India
    • Novartis Investigator Site
  • Coimbatore, India
    • Novartis Investigator Site
  • Goa, India
    • Novartis Investigator Site
  • Hyderabad, India
    • Novartis Investigator Site
  • Jaipur, India
    • Novartis Investigator Site
  • Kerala, India
    • Novartis Investigator Site
  • Mangalore, India
    • Novartis Investigator Site
  • Mumbai, India
    • Novartis Investigator Site
  • Vellore, India
    • Novartis Investigator Site
• Italy
  • Ancona, Italy
    • Novartis Investigator Site
  • Arenzano, Italy
    • Novartis Investigator Site
  • Ascoli Piceno, Italy
    • Novartis Investigative Site
  • Brescia, Italy
    • Novartis Investigator Site
  • Cagliari, Italy
    • Novartis Investigator Site
  • Chieti, Italy
    • Novartis Investigator Site
  • Ferrara, Italy
    • Novartis Investigator Site
  • Milan, Italy
    • Novartis Investigator Site
  • Milano, Italy
    • Novartis Investigator Site
  • Orbassano, Italy
    • Novartis Investigator Site
  • Palermo, Italy
    • Novartis Investigator Site
  • Reggio Emilia, Italy
    • Novartis Investigator Site
  • Rome, Italy
    • Novartis Investigator Site
  • Sesto, Italy
    • Novartis Investigator Site
  • Siena, Italy
    • Novartis Investigator Site
  • Terni, Italy
    • Novartis Investigator Site
• Peru
  • Callao, Peru
    • Novartis Investigator Site
  • Miraflores, Peru
    • Novartis Investigator Site
  • San Borja, Peru
    • Novartis Investigator Site
  • San Isidro, Peru
    • Novartis Investigator Site
  • San Martin de Porres, Peru
    • Novartis Investigator Site
  • Surco, Peru
    • Novartis Investigator Site
• Russian Federation
  • Ekaterinburg, Russian Federation
    • Novartis Investigator Site
  • Kazan, Russian Federation
    • Novartis Investigator Site
  • Moscow, Russian Federation
    • Novartis Investigator Site
  • Saint Petersburg, Russian Federation
    • Novartis Investigator Site
  • Samara, Russian Federation
    • Novartis Investigator Site
  • St Petersburg, Russian Federation
    • Novartis Investigator Site
  • Yaroslavl, Russian Federation
    • Novartis Investigator Site
  • Yekaterinburg, Russian Federation
    • Novartis Investigator Site
• Slovakia
  • Bardejov, Slovakia
    • Novartis Investigator Site
  • Bratislava, Slovakia
    • Novartis Investigator Site
  • Kosice, Slovakia
    • Novartis Investigator Site
  • Kovice, Slovakia
    • Novartis Investigator Site
  • Spisska, Slovakia
    • Novartis Investigator Site
• Taiwan
  • Changhua, Taiwan
    • Novartis Investigator Site
  • Kaohsiung, Taiwan
    • Novartis Investigator Site
  • Kaohusing, Taiwan
    • Novartis Investigator Site
  • Lin-ko, Taiwan
    • Novartis Investigator Site
  • Taichung, Taiwan
    • Novartis Investigator Site
  • Taipei, Taiwan
    • Novartis Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Clinical diagnosis of moderate to severe Chronic Obstructive Pulmonary Disease (COPD) as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2006 Guidelines (mandatory) and including:

• Smoking history of at least 20 pack years
• Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) < 80% predicted and >or= 30% of predicted normal value
• Post-bronchodilator FEV1/FVC < 70%

("Post" defined as within 30 minutes of inhalation of 400 µg salbutamol)

Exclusion Criteria:

• Pregnant or nursing (lactating) women and women of child-bearing potential UNLESS they meet pre-specified definitions of post-menopausal or are using pre-specified acceptable methods of contraception
• Hospitalisation for COPD exacerbation in the 6 weeks prior to Visit 1 or during run-in
• Patients requiring oxygen therapy for chronic hypoxemia (typically >15h/day)
• Respiratory tract infection within 6 weeks prior to Visit 1 and during the run-in period
• Concomitant pulmonary disease
• Asthma history (eosinophils > 400/mm3; symptoms prior to age 40). Includes history of childhood asthma
• History of long QTc syndrome or QTc interval > 450 ms for males and >470 ms for females
• Patients who have a clinically significant condition or a clinically relevant laboratory abnormality
• History of reactions to sympathomimetic amines or inhaled medication
• Inability to use the dry powder devices or perform spirometry
• Irregular day/night, wake/sleep cycles, e.g. shift workers
• Certain medications for COPD and allied conditions such as long acting bronchodilators must not be used prior to Visit 1 and for a pre-specified minimum washout period
• Patients unable or unwilling to complete a patient diary

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Indacaterol 150 μg; Indacaterol 150 μg once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol 150 μg; Indacaterol 150 μg once daily (o.d) inhaled; Drug: Placebo to Salmeterol; Placebo to salmeterol delivered via a proprietary dry powder inhaler
Placebo Comparator: Placebo; Placebo to Indacaterol once daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Placebo to Salmeterol delivered twice daily via a proprietary dry powder inhaler in the morning and in the evening. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Placebo to Salmeterol; Placebo to salmeterol delivered via a proprietary dry powder inhaler; Drug: Placebo to Indacaterol; Placebo to Indacaterol inhaled via SDDPI.
Active Comparator: Salmeterol 50 μg; Salmeterol 50 μg twice daily delivered via a proprietary dry powder inhaler in the morning and in the evening. Placebo to Indacaterol daily in the morning, inhaled via a single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Placebo to Indacaterol; Placebo to Indacaterol inhaled via SDDPI.; Drug: Salmeterol 50 μg; Salmeterol 50 μg twice daily (b.i.d) delivered via a proprietary dry powder inhaler

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment	Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 10 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 Weeks of Treatment	SGRQ is a health related quality of life questionnaire consisting of 76 items in three sections: symptoms, activity and impacts. The total score is 0 to 100 with a higher score indicating poorer health status. The mixed model used baseline SGRQ total score, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates.	Week 12
Percentage of COPD "Days of Poor Control" During 26 Weeks of Treatment	Participants rated their symptoms on a scale of 0=none to 3=severe. A Chronic Obstructive Pulmonary Disease (COPD) "day of poor control" was defined as any day in the participants diary with a score >=2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). The mixed model used baseline percentage of "days of poor control", FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and one hour post inhalation of ipratropium as covariates.	Up to 26 weeks

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• Jones PW, Mahler DA, Gale R, Owen R, Kramer B. Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respir Med. 2011 Jun;105(6):892-9. doi: 10.1016/j.rmed.2011.02.013. Epub 2011 Mar 11.
• Worth H, Chung KF, Felser JM, Hu H, Rueegg P. Cardio- and cerebrovascular safety of indacaterol vs formoterol, salmeterol, tiotropium and placebo in COPD. Respir Med. 2011 Apr;105(4):571-9. doi: 10.1016/j.rmed.2010.11.027. Epub 2011 Jan 11.
• Yelensky R, Li Y, Lewitzky S, Leroy E, Hurwitz C, Rodman D, Trifilieff A, Paulding CA. A pharmacogenetic study of ADRB2 polymorphisms and indacaterol response in COPD patients. Pharmacogenomics J. 2012 Dec;12(6):484-8. doi: 10.1038/tpj.2011.54. Epub 2011 Dec 13.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: December 4, 2007
• First Submitted That Met QC Criteria: December 4, 2007
• First Posted (Estimate): December 5, 2007

Study Record Updates

• Last Update Posted (Estimate): August 18, 2011
• Last Update Submitted That Met QC Criteria: July 22, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Chronic obstructive pulmonary disease, indacaterol, salmeterol, placebo controlled
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Salmeterol Xinafoate
• Other Study ID Numbers: CQAB149B2336