26 Week Efficacy, Safety and Tolerability Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)
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| ClinicalTrials.gov Identifier: NCT00463567 |
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Recruitment Status :
Completed
First Posted : April 20, 2007
Results First Posted : August 18, 2011
Last Update Posted : August 18, 2011
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Pulmonary Disease, Chronic Obstructive COPD Lung Diseases, Obstructive | Drug: Indacaterol Drug: Formoterol (12 µg b.i.d.) Drug: Tiotropium (18 µg o.d.) Drug: Placebo to Indacaterol Drug: Placebo to Formoterol | Phase 2 Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 2059 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A 26-week Treatment, Multicenter, Randomized, Double Blind, Double Dummy, Placebo-controlled, Adaptive, Seamless, Parallel-group Study to Assess the Efficacy, Safety and Tolerability of Two Doses of Indacaterol (Selected From 75, 150, 300 & 600 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease Using Blinded Formoterol (12 µg b.i.d.) and Open Label Tiotropium (18 µg o.d.) as Active Controls |
| Study Start Date : | April 2007 |
| Actual Primary Completion Date : | August 2008 |
| Actual Study Completion Date : | August 2008 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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. |
Drug: Indacaterol
In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI). Drug: Placebo to Indacaterol In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI). Drug: Placebo to Formoterol In the morning and in the evening, placebo to formoterol delivered via Aerolizer. |
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Experimental: 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. |
Drug: Indacaterol
In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI). Drug: Placebo to Indacaterol In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI). Drug: Placebo to Formoterol In the morning and in the evening, placebo to formoterol delivered via Aerolizer. |
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Active Comparator: 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. |
Drug: Tiotropium (18 µg o.d.)
Tiotropium 18 µg once daily (o.d.) dry powder capsules delivered via a SDDPI. |
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Placebo Comparator: 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. |
Drug: Placebo to Indacaterol
In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI). Drug: Placebo to Formoterol In the morning and in the evening, placebo to formoterol delivered via Aerolizer. |
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Experimental: 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. |
Drug: Indacaterol
In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI). Drug: Placebo to Indacaterol In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI). Drug: Placebo to Formoterol In the morning and in the evening, placebo to formoterol delivered via Aerolizer. |
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Experimental: 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. |
Drug: Indacaterol
In the morning, Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI). Drug: Placebo to Formoterol In the morning and in the evening, placebo to formoterol delivered via Aerolizer. |
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Active Comparator: 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. |
Drug: Formoterol (12 µg b.i.d.)
Formoterol 12 µg twice daily (b.i.d.) in the morning and in the evening via an aerolizer. Drug: Placebo to Indacaterol In the morning, Placebo to Indacaterol once daily (o.d.) orally inhaled via a single dose dry powder inhaler (SDDPI). |
- 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 ]FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 h 10 min and the 23 h 45 min post dose values. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates.
- The Percentage of "Days of Poor Control" Reported Over the 26 Week Treatment Period [ Time Frame: up to 26 weeks ]A Chronic Obstructive Pulmonary Disease (COPD) "day of poor control" was defined as any day in the participant's diary with a score ≥2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). Score for each symptom ranges from 0-3; a higher number indicates a more severe symptom. The model contained baseline percentage of "days of poor control" as well as FEV1 reversibility components as covariates.
- 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 ]
Interim Analysis: Stage 1.
Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 h 10 min and the 23 h 45 min post dose values. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates.
- 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 ]
Interim Analysis: Stage 1.
Spirometry was conducted according to internationally accepted standards. Standardized with respect to time (AUC 1h-4h) for FEV1 measurements taken from 1 hour to 4 hour post morning dose on Day 14. Standardized FEV1 AUC was calculated by the trapezoidal rule. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates.
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| Ages Eligible for Study: | 40 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male and female adults aged ≥ 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure
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Co-operative outpatients with a diagnosis of COPD (moderate to severe as classified by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) Guidelines, 2005) and:
- Smoking history of at least 20 pack years
- Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value.
- Post-bronchodilator FEV1/FVC < 70% (Post refers to within 30 min of inhalation of 400 µg of salbutamol)
Exclusion Criteria:
- Pregnant or lactating females
- Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period
- Patients requiring long term oxygen therapy (> 15 h a day)
- Patients who have had a respiratory tract infection 6 weeks prior to V1 (with further criteria)
- Patients with concomitant pulmonary disease, pulmonary tuberculosis, or clinically significant bronchiectasis
- Patients with a history of asthma (with further criteria)
- Patients with Type I or uncontrolled Type II diabetes
- Patients with contraindications for tiotropium
- Patients who have clinically relevant laboratory abnormalities or a clinically significant abnormality
- Any patient with active cancer or a history of cancer with less than 5 years disease free survival time
- Patients with a history of long QT syndrome or whose QTc interval is prolonged
- Patients with a hypersensitivity to any of the study drugs or drugs with similar chemical structures
- Patients who have had treatment with the investigational drug (with further criteria)
- Patients who have had live attenuated vaccinations within 30 days prior to visit 1, or during run-in period
- Patients with known history of non compliance to medication
- Patients unable to satisfactorily use a dry powder inhaler device or perform spirometry measurements
Other protocol-defined inclusion/exclusion criteria may apply
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00463567
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| Study Chair: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| Responsible Party: | external affairs, Novartis |
| ClinicalTrials.gov Identifier: | NCT00463567 |
| Other Study ID Numbers: |
CQAB149B2335S |
| First Posted: | April 20, 2007 Key Record Dates |
| Results First Posted: | August 18, 2011 |
| Last Update Posted: | August 18, 2011 |
| Last Verified: | July 2011 |
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indacaterol long acting beta-2 agonist |
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Lung Diseases Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Respiratory Tract Diseases Chronic Disease Disease Attributes Pathologic Processes Formoterol Fumarate Tiotropium Bromide Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents |
Physiological Effects of Drugs Anti-Asthmatic Agents Respiratory System Agents Adrenergic beta-2 Receptor Agonists Adrenergic beta-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Parasympatholytics Cholinergic Antagonists Cholinergic Agents |