26 Week Efficacy, Safety and Tolerability Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00463567
First received: April 19, 2007
Last updated: July 22, 2011
Last verified: July 2011
Results First Received: July 22, 2011  
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
Conditions: Pulmonary Disease, Chronic Obstructive
COPD
Lung Diseases, Obstructive
Interventions: Drug: Indacaterol
Drug: Formoterol (12 µg b.i.d.)
Drug: Tiotropium (18 µg o.d.)
Drug: Placebo to Indacaterol
Drug: Placebo to Formoterol

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This study consisted of two stages: a dose selection stage (Stage 1, 2 weeks) from which 2 out of 4 Indacaterol doses were selected following interim analysis to continue into Stage 2 for comparisons of efficacy, safety, and tolerability for total treatment of up to 26 weeks.

Reporting Groups
  Description
Indacaterol 150 µg (Continued Into Stage 2)

In the morning, Indacaterol 150 µg once daily orally inhaled via a single dose dry powder inhaler (SDDPI) + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1.

Daily Inhaled Corticosteroid (ICS) monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Indacaterol 300 µg (Continued Into Stage 2)

In the morning, Indacaterol 300 µg once daily orally inhaled via a SDDPI + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Tiotropium (Continued Into Stage 2)

Tiotropium 18 µg dry powder capsules delivered (open label) via manufacturer's proprietary SDDPI, (Handihaler®). Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Placebo (Continued Into Stage 2)

In the morning, Placebo to Indacaterol delivered via two SDDPI devices + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Indacaterol 75 µg (Not Continued Into Stage 2)

In the morning, Indacaterol 75 µg once daily orally inhaled via a SDDPI + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Indacaterol 600 µg (Not Continued Into Stage 2)

In the morning, 2 capsules of Indacaterol 300 µg once daily orally inhaled via two SDDPI devices + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Formoterol 12 µg (Not Continued Into Stage 2)

In the morning, Placebo to Indacaterol delivered via two SDDPI devices + Formoterol 12 µg delivered via Aerolizer. In evening, Formoterol 12 µg delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.


Participant Flow:   Overall Study
    Indacaterol 150 µg (Continued Into Stage 2)     Indacaterol 300 µg (Continued Into Stage 2)     Tiotropium (Continued Into Stage 2)     Placebo (Continued Into Stage 2)     Indacaterol 75 µg (Not Continued Into Stage 2)     Indacaterol 600 µg (Not Continued Into Stage 2)     Formoterol 12 µg (Not Continued Into Stage 2)  
STARTED     420 [1]   418     420     425     130     123     123  
Safety Population: Received Study Drug     416     416     415     418     127 [2]   122 [2]   122 [2]
COMPLETED     325     341     331     294     107     102     112  
NOT COMPLETED     95     77     89     131     23     21     11  
Adverse Event                 29                 26                 17                 46                 10                 10                 4  
Withdrawal by Subject                 29                 22                 20                 37                 6                 5                 1  
Protocol Deviation                 13                 9                 14                 11                 1                 1                 2  
Lost to Follow-up                 12                 6                 13                 8                 1                 1                 1  
Administrative problems                 5                 3                 6                 9                 3                 2                 2  
Lack of Efficacy                 4                 9                 9                 17                 1                 0                 1  
Abnormal lab value(s)                 1                 1                 2                 1                 1                 0                 0  
Abnormal test procedure result(s)                 1                 1                 6                 2                 0                 2                 0  
Death                 1                 0                 2                 0                 0                 0                 0  
[1] Randomized Participants
[2] 'Completed' indicates the number of patients in the interim analysis.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Indacaterol 150 µg (Continued Into Stage 2)

In the morning, Indacaterol 150 µg once daily orally inhaled via a single dose dry powder inhaler (SDDPI) + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1.

Daily Inhaled Corticosteroid (ICS) monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Indacaterol 300 µg (Continued Into Stage 2)

In the morning, Indacaterol 300 µg once daily orally inhaled via a SDDPI + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Tiotropium 18 µg (Continued Into Stage 2)

Tiotropium 18 µg dry powder capsules delivered (open label) via manufacturer's proprietary SDDPI, (Handihaler®). Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Placebo (Continued Into Stage 2)

In the morning, Placebo to Indacaterol delivered via two SDDPI devices + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 and continued treatment up to 26 weeks in Stage 2. Placebo to Formoterol inhalation in the morning and in the evening was discontinued after Stage 1.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Indacaterol 75 µg (Not Continued Into Stage 2)

In the morning, Indacaterol 75 µg once daily orally inhaled via a SDDPI + Placebo to Indacaterol delivered via SDDPI + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Indacaterol 600 µg (Not Continued Into Stage 2)

In the morning, 2 capsules of Indacaterol 300 µg once daily orally inhaled via two SDDPI devices + Placebo to Formoterol delivered via Aerolizer. In the evening, Placebo to Formoterol delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Formoterol 12 µg (Not Continued Into Stage 2)

In the morning, Placebo to Indacaterol delivered via two SDDPI devices + Formoterol 12 µg delivered via Aerolizer. In evening, Formoterol 12 µg delivered via Aerolizer. Participated in the 2 week Stage 1 but did not continue to Stage 2.

Daily ICS monotherapy (if applicable) was to remain stable and Salbutamol/albuterol was available for rescue use throughout study.

Total Total of all reporting groups

Baseline Measures
    Indacaterol 150 µg (Continued Into Stage 2)     Indacaterol 300 µg (Continued Into Stage 2)     Tiotropium 18 µg (Continued Into Stage 2)     Placebo (Continued Into Stage 2)     Indacaterol 75 µg (Not Continued Into Stage 2)     Indacaterol 600 µg (Not Continued Into Stage 2)     Formoterol 12 µg (Not Continued Into Stage 2)     Total  
Number of Participants  
[units: participants]
  416     416     415     418     127     122     122     2036  
Age, Customized [1]
[units: participants]
               
Between 40 and 64 years     214     230     215     215     58     60     56     1048  
≥65 years     202     186     200     203     69     62     66     988  
Gender  
[units: participants]
               
Female     157     153     146     163     51     48     52     770  
Male     259     263     269     255     76     74     70     1266  
[1] Baseline Measures were based on the Safety Population that included all participants who received at least one dose of study drug.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Trough Forced Expiratory Volume in 1 Second (FEV1) Assessed by Spirometry 24 Hour Post Dose After 12 Weeks of Treatment   [ Time Frame: after 12 weeks of treatment ]

2.  Secondary:   The Percentage of "Days of Poor Control" Reported Over the 26 Week Treatment Period   [ Time Frame: up to 26 weeks ]

3.  Other Pre-specified:   Trough Forced Expiratory Volume in 1 Second (FEV1) Assessed by Spirometry 24 Hour Post Dose After 2 Weeks of Treatment   [ Time Frame: Day 15, After 2 Weeks of treatment in Stage 1 ]

4.  Other Pre-specified:   Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 1 Hour to 4 Hour Post Morning Dose After 2 Weeks of Treatment   [ Time Frame: Day 14, After 2 Weeks of treatment in Stage 1 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided by Novartis

Publications automatically indexed to this study:

Responsible Party: external affairs, Novartis
ClinicalTrials.gov Identifier: NCT00463567     History of Changes
Other Study ID Numbers: CQAB149B2335S
Study First Received: April 19, 2007
Results First Received: July 22, 2011
Last Updated: July 22, 2011
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Germany: Federal Institute for Drugs and Medical Devices
Spain: Spanish Agency of Medicines
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Canada: Health Canada
Italy: Direzione Generale di Sanità Veterinaria e degli Alimenti
Korea: Food and Drug Administration
United States: Food and Drug Administration
Taiwan: Department of Health
India: Institutional Review Board
Sweden: Medical Products Agency
Turkey: Ministry of Health
Venezuela: Intituto Nacional de Higiene Rafael Rangel