Efficacy and Safety of Indacaterol Plus Tiotropium Versus Tiotropium Alone in Patients With Chronic Obstructive Pulmonary Disease - Full Text View

Sponsor:	Novartis Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00846586

Purpose

This study assessed the efficacy and safety of indacaterol (150 µg once daily [od]) when combined with tiotropium (18 µg od) versus tiotropium (18 µg od) treatment alone in patients with chronic obstructive pulmonary disease (COPD)

Condition	Intervention	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: Indacaterol 150 μg Drug: Tiotropium 18 μg Drug: Placebo to indacaterol	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind, Controlled, Parallel-group, 12-week Study to Compare the Efficacy and Safety of the Combination of Indacaterol 150 µg Once Daily With Open Label Tiotropium 18 µg Once Daily Versus Open Label Tiotropium 18 µg Once Daily in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:

MedlinePlus related topics: COPD (Chronic Obstructive Pulmonary Disease)

Drug Information available for: Tiotropium bromide Tiotropium Indacaterol

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 8 Hours Post-dose at the End of Treatment (Week 12) [ Time Frame: From 5 minutes to 8 hours post-dose at the end of treatment (Week 12, Day 84) ] [ Designated as safety issue: No ]
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, 4, 6, and 8 hours post-dose at the end of the study (Week 12, Day 84). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Secondary Outcome Measures:

Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85) [ Time Frame: 24 hours post-dose at the end of treatment (Week 12 + 1 day, Day 85) ] [ Designated as safety issue: No ]
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of the study (Week 12 + 1 day, Day 85). The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 8 Hours Post-dose on Day 1 [ Time Frame: From 5 minutes to 8 hours post-dose on Day 1 ] [ Designated as safety issue: No ]
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2 [ Time Frame: 24 hours post-dose on Day 2 ] [ Designated as safety issue: No ]
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 2. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose on Day 1 [ Time Frame: From 5 minutes to 4 hours post-dose on Day 1 ] [ Designated as safety issue: No ]
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, and 4 hours post-dose on Day 1. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at the End of Treatment (Week 12) [ Time Frame: From 5 minutes to 4 hours post-dose at the end of treatment (Week 12) ] [ Designated as safety issue: No ]
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, and 4 hours post-dose at the end of treatment (Week 12). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.

Enrollment:	1134
Study Start Date:	March 2009
Study Completion Date:	March 2010
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Indacaterol 150 μg and tiotropium 18 μg Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol 150 μg Indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device. Drug: Tiotropium 18 μg Tiotropium was supplied in powder filled capsules together the manufacture's proprietary inhalation device (HandiHaler®).
Active Comparator: Tiotropium 18 μg Patients inhaled placebo to indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Placebo to indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Tiotropium 18 μg Tiotropium was supplied in powder filled capsules together the manufacture's proprietary inhalation device (HandiHaler®). Drug: Placebo to indacaterol Placebo to indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.

Arms

Assigned Interventions

Experimental: Indacaterol 150 μg and tiotropium 18 μg

Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Indacaterol 150 μg

Indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.

Drug: Tiotropium 18 μg

Tiotropium was supplied in powder filled capsules together the manufacture's proprietary inhalation device (HandiHaler®).

Active Comparator: Tiotropium 18 μg

Patients inhaled placebo to indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Placebo to indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Tiotropium 18 μg

Tiotropium was supplied in powder filled capsules together the manufacture's proprietary inhalation device (HandiHaler®).

Drug: Placebo to indacaterol

Placebo to indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.

Eligibility

Ages Eligible for Study:	40 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of chronic obstructive pulmonary disease (COPD) (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease [GOLD] Guidelines, 2007) and:
1. Smoking history of at least 10 pack-years
2. Post-bronchodilator forced expiratory volume in 1 second (FEV1) ≤ 65% and ≥ 30% of the predicted normal value
3. Post-bronchodilator FEV1/FVC (force vital capacity) < 70%

Exclusion Criteria:

Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment or antibiotics and/or hospitalization in the 6 weeks prior to screening or during the run-in period
Patients who have had a respiratory tract infection within 6 weeks prior to screening or during the run-in period
Patients with a body mass index less than 15 or more than 40 kg/m^2
Patients with concomitant pulmonary disease
Patients with a history of asthma
Patients with diabetes Type I or uncontrolled diabetes Type II
Any patient with lung cancer or a history of lung cancer
Patients with a history of certain cardiovascular comorbid conditions

Other protocol-defined inclusion/exclusion criteria applied to the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00846586

Show 138 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00846586 History of Changes
Other Study ID Numbers:	CQAB149B2341
Study First Received:	February 15, 2009
Results First Received:	July 22, 2011
Last Updated:	July 22, 2011
Health Authority:	United States: Food and Drug Administration; Denmark: Danish Medicines Agency; Spain: Spanish Agency of Medicines; Turkey: Ministry of Health; Australia: Department of Health and Ageing Therapeutic Goods Administration; South Africa: Medicines Control Council; Philippines: Bureau of Food and Drugs; Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos; Guatemala: Comisión para la Evaluación de Ensayos Clínicos Ministerio de Salud Pública y Asistencia Social; Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Keywords provided by Novartis:

chronic obstructive pulmonary disease
COPD
indacaterol
tiotropium
bronchodilation

Additional relevant MeSH terms:

Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Tiotropium
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

Pharmacologic Actions
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012