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A Study to Compare the Lung Effect of Indacaterol and Tiotropium in Chronic Obstructive Pulmonary Disease (COPD)

Phase 3
Completed
Conditions
Chronic Obstructive Pulmonary Disease
Interventions
Registration Number
NCT00900731
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

This study compared the lung effects of indacaterol to those of tiotropium in patients with moderate to severe chronic obstructive pulmonary disease (COPD) over a 12 week period.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1598
Inclusion Criteria
  • Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2007) and:
  • a) Smoking history of at least 10 pack-years
  • b) Post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% of the predicted normal value
  • c) Post-bronchodilator FEV1/FVC (forced vital capacity) < 70%
Exclusion Criteria
  • Patients who have received systemic corticosteroids or antibiotics and/or was hospitalized for a COPD exacerbation in the 6 weeks prior to screening
  • Patients who have had a respiratory tract infection within 6 weeks prior to screening
  • 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Indacaterol 150 µgPlacebo to tiotropiumParticipants received indacaterol 150 μg delivered via a single-dose dry-powder inhaler (SDDPI) plus placebo to tiotropium delivered via the manufacturer's proprietary inhalation device (HandiHaler®) once daily in the morning. Participants were permitted to take salbutamol/albuterol as a rescue medication.
Indacaterol 150 µgIndacaterol 150 μgParticipants received indacaterol 150 μg delivered via a single-dose dry-powder inhaler (SDDPI) plus placebo to tiotropium delivered via the manufacturer's proprietary inhalation device (HandiHaler®) once daily in the morning. Participants were permitted to take salbutamol/albuterol as a rescue medication.
Tiotropium 18 µgTiotropium 18 μgParticipants received tiotropium 18 μg delivered via the manufacturer's proprietary inhalation device (HandiHaler®) plus placebo to indacaterol delivered via a single-dose dry-powder inhaler (SDDPI) once daily in the morning. Participants were permitted to take salbutamol/albuterol as a rescue medication.
Tiotropium 18 µgPlacebo to indacaterolParticipants received tiotropium 18 μg delivered via the manufacturer's proprietary inhalation device (HandiHaler®) plus placebo to indacaterol delivered via a single-dose dry-powder inhaler (SDDPI) once daily in the morning. Participants were permitted to take salbutamol/albuterol as a rescue medication.
Primary Outcome Measures
NameTimeMethod
Trough Forced Expiratory Volume in 1 Second (FEV1) at End of Treatment (Week 12)End of treatment (Week 12)

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, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.

Secondary Outcome Measures
NameTimeMethod
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at the End of Treatment (Week 12)5 minutes to 4 hours post-dose at the end of treatment (week 12)

Spirometry was conducted according to internationally accepted standards. FEV1 was measured at 5 and 30 minutes; and 1, 2, and 4 hours post-dose on Week 12. Standardized FEV1 AUC (5 minutes-4 hour) post-dose at week 12 was calculated based on the trapezoidal rule, and was adjusted for the area per time unit by using the scheduled time of measurements for FEV1. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.

Transition Dyspnea Index (TDI) Focal Score After 12 Weeks of Treatment12 weeks

TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9 with a negative score indicating a deterioration from baseline. A 1 unit difference in the TDI focal score is clinically significant. Mixed model used baseline dyspnea index, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.

Quality of Life Assessment With St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 Weeks of Treatment12 weeks

SGRQ is a health related quality of life questionnaire consisting of 50 items in three domains: symptoms (frequency and severity), activity (that cause or are limited by breathlessness) and impacts (social functioning \& psychological disturbances resulting from airway disease). The total score is 0 to 100 with a higher score indicating greater impairment of health status. Mixed model used baseline SGRQ, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.

Change From Baseline in the Mean Number of Puffs Per Day of Rescue Medication Over the Study Duration (From Day 1 to Week 12)Baseline, up to 12 weeks

Participants recorded the number of puffs of rescue medication taken in the previous 12 hours each morning and evening in an electronic diary. The number of puffs per day over the 12 weeks of treatment was divided by the number of days to derive the mean number per day of puffs of rescue medication for each participant. Mixed model used baseline number of puffs per day of rescue medication, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.

Change From Baseline in the Mean Number Per Day of Daytime Puffs of Rescue Medication Over the Study Duration (From Day 1 to Week 12)Baseline, up to 12 weeks

Participants recorded the number of puffs of rescue medication taken in the previous 12 hours each evening in an electronic diary. The number of daytime puffs per day over the 12 weeks of treatment was divided by the number of days to derive the mean number per day of daytime puffs of rescue medication for each participant. Mixed model used baseline number of daytime puffs per day of rescue medication, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.

Change From Baseline in the Mean Number Per Day of Nighttime Puffs of Rescue Medication Over the Study Duration (From Day 1 to Week 12)Baseline, up to 12 weeks

Participants recorded the number of puffs of rescue medication taken in the previous 12 hours each morning in an electronic diary. The number of nighttime puffs per day over the 12 weeks of treatment was divided by the number of days to derive the mean number per day of nighttime puffs of rescue medication for each participant. Mixed model used baseline number of nighttime puffs per day of rescue medication, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.

Percentage of Days With no Rescue Medication Use During the 12 Weeks of TreatmentUp to 12 weeks

A day with no rescue medication was defined as any day in the diary that the participant used no puffs of rescue medication. The percentage of days with no rescue medication was calculated by dividing the number of days with no rescue medication over the 12 week treatment period by the number of evaluable days and multiplying by 100. Mixed model used baseline percentage of days with no rescue medication, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.

Trial Locations

Locations (4)

Novartis Investigative SIte

🇨🇦

Quebec, Canada

Novartis Investigator Site

🇬🇧

Watford, United Kingdom

Novartis Investigative Site

🇹🇷

Yenisehir/Izmir, Turkey

Novartis Investigative Center

🇺🇸

St Charles, Missouri, United States

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