Safety, Tolerability and Efficacy of Indacaterol in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

A 26-week Extension to a 26-week Treatment, Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptive, Seamless, Parallel-group Study to Assess Safety, Tolerability and Efficacy of Two Doses of Indacaterol (150 and 300 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease

This study evaluated the 1 year safety, tolerability and efficacy of indacaterol against placebo in the treatment of Chronic Obstructive Pulmonary Disease (COPD) patients

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Indacaterol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 415
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Novartis Investigative Site
  • Rosario, Argentina
    • Novartis Investigative Site
• Canada
  • Ajax, Canada
    • Novartis Investigative Site
  • Calgary, Canada
    • Novartis Investigative Site
  • Gatineau, Canada
    • Novartis Investigative Site
  • Moncton, Canada
    • Novartis Investigative Site
  • Montreal, Canada
    • Novartis Investigative Site
  • Niagara Falls, Canada
    • Novartis Investigative Site
  • Ottawa, Canada
    • Novartis Investigative Site
  • Quebec, Canada
    • Novartis Investigative Site
  • Saskatoon, Canada
    • Novartis Investigative Site
  • Sherbrooke, Canada
    • Novartis Investigative Site
  • St-Romuald, Canada
    • Novartis Investigative Site
  • St. John, Canada
    • Novartis Investigative Site
  • St. John's, Canada
    • Novartis Investigative Site
  • Toronto, Canada
    • Novartis Investigative Site
  • Trois-Rivières, Canada
    • Novartis Investigative Site
  • Vancouver, Canada
    • Novartis Investigative Site
  • Windsor, Canada
    • Novartis Investigative Site
  • Winnipeg, Canada
    • Novartis Investigative Site
• Germany
  • Augsburg, Germany
    • Novartis Investigative Site
  • Bad Segeberg, Germany
    • Novartis Investigative Site
  • Berlin, Germany
    • Novartis Investigative Site
  • Bielefeld, Germany
    • Novartis Investigative Site
  • Bonn, Germany
    • Novartis Investigative Site
  • Dachau, Germany
    • Novartis Investigative Site
  • Hamburg, Germany
    • Novartis Investigative Site
  • Hoyerswerda, Germany
    • Novartis Investigative Site
  • Kaufbeuren, Germany
    • Novartis Investigative Site
  • Landsberg, Germany
    • Novartis Investigative Site
  • Leipzig, Germany
    • Novartis Investigative Site
  • Mainz, Germany
    • Novartis Investigative Site
  • Muenchen, Germany
    • Novartis Investigative Site
  • Oranienburg, Germany
    • Novartis Investigative Site
  • Oschersleben, Germany
    • Novartis Investigative Site
  • Potsdam, Germany
    • Novartis Investigative Site
  • Ratingen, Germany
    • Novartis Investigative Site
  • Steinfurt-Borghorst, Germany
    • Novartis Investigative Site
• India
  • Bangalore, India
    • Novartis Investigator Site
  • Chennai, India
    • Novartis Investigative Site
  • Coimbatore, India
    • Novartis Investigator Site
  • Coimbatore, India
    • Novartis Investigative Site
  • Hyderabaad, India
    • Novartis Investigator Site
  • Indore, India
    • Novartis Investigator Site
  • Jaipur, India
    • Novartis Investigator Site
  • Kolkata, India
    • Novartis Investigator Site
  • Ludhiana, India
    • Novartis Investigator Site
  • Mumbai, India
    • Novartis Investigative Site
  • Panjim, India
    • Novartis Investigator Site
  • Trivandrum, India
    • Novartis Investigator Site
• Italy
  • Bologna, Italy
    • Novartis Investigator Site
  • Busto Arsizio, Italy
    • Novartis Investigator Site
  • Catania, Italy
    • Novartis Investigator Site
  • Catanzaro, Italy
    • Novartis Investigator Site
  • Crema, Italy
    • Novartis Investigator Site
  • Ferrara, Italy
    • Novartis Investigator Site
  • Firenze, Italy
    • Novartis Investigator Site
  • Messina, Italy
    • Novartis Investigator Site
  • Milano, Italy
    • Novartis Investigator Site
  • Pisa, Italy
    • Novartis Investigator Site
  • Roma, Italy
    • Novartis Investigator Site
  • Rozzano, Italy
    • Novartis Investigator Site
  • Siena, Italy
    • Novartis Investigator Site
  • Sottomarina, Italy
    • Novartis Investigator Site
• Spain
  • Alicante, Spain
    • Novartis Investigator Site
  • Alzira, Spain
    • Novartis Investigator Site
  • Barcelona, Spain
    • Novartis Investigator Site
  • Burgos, Spain
    • Novartis Investigator Site
  • Cordoba, Spain
    • Novartis Investigator Site
  • Girona, Spain
    • Novartis Investigator Site
  • Gladakano, Spain
    • Novartis Investigator Site
  • Jerez de Frontera, Spain
    • Novartis Investigator Site
  • La Coruna, Spain
    • Novartis Investigator Site
  • Las Palmas de Gran Canaria, Spain
    • Novartis Investigator Site
  • Las Palmas de Gran Canarias, Spain
    • Novartis Investigator Site
  • Lugo, Spain
    • Novartis Investigator Site
  • Madrid, Spain
    • Novartis Investigator Site
  • Malaga, Spain
    • Novartis Investigator Site
  • Orense, Spain
    • Novartis Investigator Site
  • Oviedo, Spain
    • Novartis Investigator Site
  • Palma De Mallorca, Spain
    • Novartis Investigator Site
  • Ponferrada, Spain
    • Novartis Investigator Site
  • Pontevedra, Spain
    • Novartis Investigative Site
  • Puerto de Sagunto, Spain
    • Novartis Investigator Site
  • Sevilla, Spain
    • Novartis Investigative Site
  • Valencia, Spain
    • Novartis Investigator Site
  • Vic, Spain
    • Novartis Investigator Site
  • Vila-real, Spain
    • Novartis Investigator Site
  • Zaragoza, Spain
    • Novartis Investigative Site
• Sweden
  • Goteborg, Sweden
    • Novartis Investigative Site
  • Jonkoping, Sweden
    • Novartis Investigator Site
  • Lidingo, Sweden
    • Novartis Investigative Site
  • Lulea, Sweden
    • Novartis Investigative Site
  • Lulea, Sweden
    • Novartis Investigator Site
  • Lund, Sweden
    • Novartis Investigator Site
• Turkey
  • Kartal/Istanbul, Turkey
    • Novartis Investigative Site
  • Mersin, Turkey
    • Novartis Investigator Site
  • Yenisehir/Izmir, Turkey
    • Novartis Investigator Site
• United States
  • Alabama
    • Homewood, Alabama, United States, 35209-6870
      • Novartis Investigative Site
    • Jasper, Alabama, United States, 35501
      • Novartis Investigative Site
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Novartis Investigative Site
    • Tucson, Arizona, United States, 85712
      • Novartis Investigative Site
  • Arkansas
    • Pine Bluff, Arkansas, United States, 71603
      • Novartis Investigative Site
  • California
    • Encinitas, California, United States, 92024-1332
      • Novartis Investigative Site
    • Fullerton, California, United States, 92835
      • Novartis Investigative Site
    • Orange, California, United States, 92869
      • Novartis Investigative Site
    • Riverside, California, United States, 92506
      • Novartis Investigative Site
    • Spring Valley, California, United States, 91978
      • Novartis Investigative Site
  • Colorado
    • Fort Collins, Colorado, United States, 80528
      • Novartis Investigative Site
    • Golden, Colorado, United States, 80401
      • Novartis Investigative Site
    • Wheat Ridge, Colorado, United States, 80033
      • Novartis Investigative Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Novartis Investigative Site
    • Largo, Florida, United States, 33770
      • Novartis Investigative Site
    • Pensacola, Florida, United States, 32504
      • Novartis Investigative Site
    • Rockledge, Florida, United States, 32955
      • Novartis Investigative Site
    • South Miami, Florida, United States, 33143
      • Novartis Investigative Site
    • Tamarac, Florida, United States, 33321
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33603
      • Novartis Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Novartis Investigative Site
    • Marietta, Georgia, United States, 30060
      • Novartis Investigative Site
  • Illinois
    • Normal, Illinois, United States, 61761
      • Novartis Investigative Site
    • O'Fallon, Illinois, United States, 62269
      • Novartis Investigative Site
    • River Forest, Illinois, United States, 60305
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Novartis Investigative Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Novartis Investigative Site
    • Iowa City, Iowa, United States, 52240
      • Novartis Investigative Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Novartis Investigative Site
  • Kentucky
    • Crescent Springs, Kentucky, United States, 41017
      • Novartis Investigative Site
    • Lexington, Kentucky, United States, 40536
      • Novartis Investigative Site
    • Lexington, Kentucky, United States, 40504
      • Novartis Investigative Site
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Novartis Investigative Site
    • Metaire, Louisiana, United States, 70002
      • Novartis Investigative Site
    • New Orleans, Louisiana, United States, 70112
      • Novartis Investigative Site
  • Maine
    • Biddeford, Maine, United States, 04005
      • Novartis Investigative Site
  • Michigan
    • Clarkston, Michigan, United States, 48346
      • Novartis Investgative Site
    • Flint, Michigan, United States, 48532
      • Novartis Investigative Site
    • Livonia, Michigan, United States, 48152
      • Novartis Investigative Site
    • Troy, Michigan, United States, 48085
      • Novartis Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Novartis Investigative Site
    • Minneapolis, Minnesota, United States, 55407
      • Novartis Investigative Site
    • Rochester, Minnesota, United States, 55905
      • Novartis Investigative Site
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Novartis Investigative Site
    • Columbia, Missouri, United States, 65212
      • Novartis Investigative Site
    • Kansas City, Missouri, United States, 64108-2677
      • Novartis Investigative Site
    • St Louis, Missouri, United States, 63141
      • Novartis Investigative Site
  • Montana
    • Billings, Montana, United States, 59102
      • Novartis Investigative Site
    • Kalispell, Montana, United States, 59901
      • Novartis Investigative Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Novartis Investigative Site
    • Omaha, Nebraska, United States, 68134
      • Novartis Investigative Site
    • Omaha, Nebraska, United States, 68130
      • Novartis Investigative Site
    • Omaha, Nebraska, United States, 68198-5885
      • Novartis Investigative Site
    • Papillion, Nebraska, United States, 68046
      • Novartis Investigative Site
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Novartis Investigative Site
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Novartis Investigative Site
  • New York
    • Elmira, New York, United States, 14905
      • Novartis Investigative Site
    • New York, New York, United States, 10016
      • Novartis Investigative Site
    • Rochester, New York, United States, 14618-2638
      • Novartis Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Novartis Investigative Site
    • Shelby, North Carolina, United States, 28150
      • Novartis Investigative Site
    • Winston Salem, North Carolina, United States, 27103
      • Novartis Investigative Site
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Novartis Investigative Site
    • Cleveland, Ohio, United States, 44109-1998
      • Novartis Investigative Site
    • Columbus, Ohio, United States, 43215
      • Novartis Investigative Site
    • Columbus, Ohio, United States, 43213
      • Novartis Investigative Site
    • Marion, Ohio, United States, 43302
      • Novartis Investigative Site
    • Sylvania, Ohio, United States, 43650
      • Novartis Investigative Site
    • Thornville, Ohio, United States, 43076
      • Novartis Investigative Site
    • Zanesville, Ohio, United States, 43701
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Novartis Investigative Site
    • Tulsa, Oklahoma, United States, 74135-2920
      • Novartis Investigative Site
  • Oregon
    • Eugene, Oregon, United States, 97404-3233
      • Novartis Investigative Site
    • Medford, Oregon, United States, 97504-8741
      • Novartis Investigative Site
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16506
      • Novartis Investigative Site
    • Pittsburgh, Pennsylvania, United States, 15243
      • Novartis Investigative Site
    • Pittsburgh, Pennsylvania, United States, 15221
      • Novartis Investigative Site
  • Rhode Island
    • Cranston, Rhode Island, United States, 02920
      • Novartis Investigative Site
    • Cumberland, Rhode Island, United States, 02864
      • Novartis Investigative Site
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Novartis Investigative Site
  • Tennessee
    • Johnson City, Tennessee, United States, 37601
      • Novartis Investigative Site
  • Texas
    • Corsicana, Texas, United States, 75110
      • Novartis Investigative Site
    • Dallas, Texas, United States, 75231
      • Novartis Investigative Site
    • El Paso, Texas, United States, 79902
      • Novartis Investigative Site
    • Fort Worth, Texas, United States, 76104
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78229
      • Novartis Investigative Site
  • Virginia
    • Abingdon, Virginia, United States, 24210
      • Novartis Investigative Site
    • Lynchburg, Virginia, United States, 24501
      • Novartis Investigative Site
    • Richmond, Virginia, United States, 23249
      • Novartis Investigative Site
  • Washington
    • Bellingham, Washington, United States, 98225
      • Novartis Investigative Site
    • Spokane, Washington, United States, 99216
      • Novartis Investigative Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209-0996
      • Novartis Investigative 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:

• Patients eligible to participate in the study extension, by definition, will have met the inclusion and exclusion criteria for the core 26 weeks and not met the withdrawal criteria for the core study B2335S at Visit 14 (the last visit of the core study B2335S and the first visit of the extension study B2335SE).

• In addition the following inclusion/exclusion criteria specified below must be met.

  1. Patients must complete Stage 2 of the core study B2335S (NCT00463567).
  2. Written informed consent to participate in the extension must be obtained.
  3. Patients must be able to comply with all study requirements.

Exclusion Criteria:

• Patients who were randomized to open-label tiotropium in Study B2335S.
• Patients who participated in Stage 1 of the core study (B2335S).
• Patients discontinued irrespective of the reason from Stage 2 of the core study.
• Patients who fail to comply with the core protocol requirements and procedures.
• Concomitant medical conditions that may interfere with interpretation of study results as defined in the core study protocol.
• Patients who in the Investigator's opinion should not participate in the extension study.

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 (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol; Indacaterol once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI)
Experimental: Indacaterol 300 µg; Indacaterol 300 µg once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI). The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol; Indacaterol once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI)
Placebo Comparator: Placebo; Placebo once-daily (o.d.) via SDDPI. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Placebo; Placebo once-daily (o.d.) via single-dose dry-powder inhaler (SDDPI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants With a Clinically Notable Pulse Rate During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo	The number of participants with newly occurring or worsening clinically notable vital sign: Pulse Rate in beats per minute (bpm) at anytime post baseline (BL) by treatment. Low Pulse Rate was defined as a pulse rate: <40 bpm or <= to 50 bpm and a decrease from baseline >= to 15 bpm. High Pulse Rate was defined as a pulse rate: >130 bpm or >= to 120 bpm and an increase from baseline >= to 15 bpm.	Up to 52 weeks
The Number of Participants With a Clinically Notable Systolic Blood Pressure During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo	The number of participants with newly occurring or worsening clinically notable vital sign: Systolic Blood Pressure (mmHg) at anytime post baseline (BL) by treatment. A Low Systolic Blood Pressure was defined as a systolic blood pressure measurement: <75 mmHg or <= to 90 mmHg and a decrease from baseline >= to 20 mmHg. A High Systolic Blood Pressure was defined as a systolic blood pressure measurement: >200 mmHg or >= to 180 mmHg and an increase from baseline >= to 20 mmHg.	Up to 52 weeks
The Number of Participants With a Clinically Notable Diastolic Blood Pressure During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo	The number of participants with newly occurring or worsening clinically notable vital sign: Diastolic Blood Pressure (mmHg) at anytime post baseline (BL) by treatment. A Low Diastolic Blood Pressure was defined as a diastolic blood pressure measurement: <40 mmHg or <= to 50 mmHg and a decrease from baseline >= to 15 mmHg. A High Diastolic Blood Pressure was defined as a diastolic blood pressure measurement: >115 mmHg or >= to 105 mmHg and an increase from baseline >= to 15 mmHg.	Up to 52 weeks
The Number of Participants With a Clinically Notable QTc Interval Value During 52 Weeks of Treatment With Indacaterol 150 µg or 300 µg Compared to Placebo	The number of participants with newly occurring or worsening clinically notable QTc Interval value at anytime post baseline. The QTc interval is calculated using Fridericia's formula: QTc= QT/cube root RR. QTc is the interval between the Q and T waves corrected for heart rate and RR is the interval between two R waves in milliseconds (ms). Notable QTC interval= >450 ms for males and >470 ms for females. The maximum QTC increase from pre to post dose at any time during the study was also tabulated with absolute and relative frequencies for categories 30- 60 ms and >60 ms.	Up to 52 weeks
Serum Potassium (mmol/L) 1 Hour Post-dose at Weeks 12, 26, 36, 44 and 52	The least squares mean of the serum potassium in mmol/L at weeks 12, 26, 36, 44 and 52. Mixed model used baseline serum potassium as a covariate.	Weeks 12, 26, 36, 44 and 52
Blood Glucose (mmol/L) 1 Hour Post Dose at Weeks 12, 26, 36, 44 and 52	The least squares mean of the blood glucose in mmol/L at weeks 12, 26, 36, 44 and 52. Mixed model used baseline blood glucose as a covariate.	Weeks 12, 26, 36, 44 and 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 52 of Treatment	Spirometry was conducted according to internationally accepted standards. The trough FEV1 was defined as the average of the FEV1 measurements taken at 23 hours 10 minutes and 23 hours 45 minutes post dose at week 52. The mixed model used baseline FEV1 as well as FEV1 reversibility components as covariates.	Week 52
Quality of Life Assessment With St George's Respiratory Questionnaire (SGRQ) Total Score at Weeks 36, 44 and 52	The least squares mean of the SGRQ total score at weeks 36, 44 and 52. Mixed model used for analysis used baseline SGRQ total score as well as FEV1 reversibility components as covariates. SGRQ is a health related quality of life questionnaire consisting of 50 items in three domains: symptoms, activity and impacts. The total score is 0 to 100 with a higher score indicating poorer health. A difference from placebo of -4 in the least squares mean SGRQ total score is considered clinically relevant.	Weeks 36, 44 and 52

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• Chapman KR, Rennard SI, Dogra A, Owen R, Lassen C, Kramer B; INDORSE Study Investigators. Long-term safety and efficacy of indacaterol, a long-acting beta(2)-agonist, in subjects with COPD: a randomized, placebo-controlled study. Chest. 2011 Jul;140(1):68-75. doi: 10.1378/chest.10-1830. Epub 2011 Feb 24.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: May 13, 2008
• First Submitted That Met QC Criteria: May 14, 2008
• First Posted (Estimate): May 15, 2008

Study Record Updates

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

More Information

Terms related to this study

• Keywords: COPD; adults; indacaterol; β2-agonist
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CQAB149B2335SE; 2008-000663-42 (EudraCT Number)