Trial Outcomes & Findings for A Crossover Study to Determine the Effect on Lung Function of Indacaterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Tiotropium as an Active Control (NCT NCT00615459)
NCT ID: NCT00615459
Last Updated: 2011-08-17
Results Overview
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the mean of FEV1 measurements at 23 h 10 min and 23 h 45 min post Day 14 dose measured on the morning of Day 15 in each treatment period. The model used for analysis contained the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
169 participants
Primary outcome timeframe
23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 15 of each treatment period
Results posted on
2011-08-17
Participant Flow
Patients were randomized to one of the 4 possible treatment sequences of the double-blind 10-week treatment phase (Week 1 - 10) to receive three out of the four study treatments. Each treatment sequence was divided into three 2-week treatment periods (I/II/III), with periods I and II followed by 2-week washout periods.
Out of total 169 randomized patients, two patients were discontinued before exposure to any treatment in period I because of administrative problems.
Participant milestones
| Measure |
Sequence 1: Placebo,Tiotropium, Indacaterol 150 μg
In period I, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. In period II, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via single dose dry powder inhaler (SDDPI). In period III, indacaterol 150 μg once daily delivered via SDDPI and placebo to tiotropium was delivered once daily via the tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
Sequence 2: Indacaterol 300 μg, Indacaterol 150 μg, Tiotropium
In period I,indacaterol 300 μg once daily delivered via single dose dry powder inhaler (SDDPI)and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period II, indacaterol 150 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period III, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via SDDPI. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
Sequence 3: Indacaterol 150 μg, Indacaterol 300 μg, Placebo
In period I, indacaterol 150 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period II, indacaterol 300 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period III, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
Sequence 4: Tiotropium, Placebo, Indacaterol 300 μg
In period I, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via SDDPI. In period II, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. In period III, indacaterol 300 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
|---|---|---|---|---|
|
Period I
STARTED
|
41
|
41
|
42
|
43
|
|
Period I
COMPLETED
|
37
|
40
|
40
|
42
|
|
Period I
NOT COMPLETED
|
4
|
1
|
2
|
1
|
|
Period II
STARTED
|
37
|
40
|
40
|
42
|
|
Period II
COMPLETED
|
36
|
40
|
40
|
41
|
|
Period II
NOT COMPLETED
|
1
|
0
|
0
|
1
|
|
Period III
STARTED
|
36
|
40
|
40
|
41
|
|
Period III
COMPLETED
|
36
|
37
|
39
|
41
|
|
Period III
NOT COMPLETED
|
0
|
3
|
1
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1: Placebo,Tiotropium, Indacaterol 150 μg
In period I, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. In period II, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via single dose dry powder inhaler (SDDPI). In period III, indacaterol 150 μg once daily delivered via SDDPI and placebo to tiotropium was delivered once daily via the tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
Sequence 2: Indacaterol 300 μg, Indacaterol 150 μg, Tiotropium
In period I,indacaterol 300 μg once daily delivered via single dose dry powder inhaler (SDDPI)and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period II, indacaterol 150 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period III, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via SDDPI. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
Sequence 3: Indacaterol 150 μg, Indacaterol 300 μg, Placebo
In period I, indacaterol 150 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period II, indacaterol 300 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period III, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
Sequence 4: Tiotropium, Placebo, Indacaterol 300 μg
In period I, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via SDDPI. In period II, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. In period III, indacaterol 300 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
|---|---|---|---|---|
|
Period I
Adverse Event
|
2
|
0
|
1
|
0
|
|
Period I
Subject withdrew consent
|
1
|
0
|
0
|
1
|
|
Period I
Abnormal test procedure results
|
1
|
1
|
1
|
0
|
|
Period II
Adverse Event
|
1
|
0
|
0
|
0
|
|
Period II
Lost to Follow-up
|
0
|
0
|
0
|
1
|
|
Period III
Adverse Event
|
0
|
1
|
0
|
0
|
|
Period III
Administrative problems
|
0
|
1
|
1
|
0
|
|
Period III
Unsatisfactory therapeutic effect
|
0
|
1
|
0
|
0
|
Baseline Characteristics
A Crossover Study to Determine the Effect on Lung Function of Indacaterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Tiotropium as an Active Control
Baseline characteristics by cohort
| Measure |
Total Patients
n=167 Participants
The safety population, included all patients who received at least one dose of study drug.
|
|---|---|
|
Age Continuous
|
64.5 years
STANDARD_DEVIATION 7.92 • n=5 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
128 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 15 of each treatment periodPopulation: The modified intent-to-treat (mITT) population, included all randomized patients who received at least one dose of study drug. Patients were analyzed according to treatment they received.
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the mean of FEV1 measurements at 23 h 10 min and 23 h 45 min post Day 14 dose measured on the morning of Day 15 in each treatment period. The model used for analysis contained the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.
Outcome measures
| Measure |
Indacaterol 150 μg
n=116 Participants
Indacaterol 150 μg once daily delivered via SDDPI and placebo to tiotropium was delivered once daily via the tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
Indacaterol 300 μg
n=119 Participants
Indacaterol 300 μg once daily delivered via single dose dry powder inhaler (SDDPI)and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=112 Participants
Tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
Placebo
n=118 Participants
Placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
|---|---|---|---|---|
|
24-hour Post-dose Trough Forced Expiratory Volume in 1 Second (FEV1) After 14 Days of Treatment
|
1.53 Liters
Standard Error 0.021
|
1.51 Liters
Standard Error 0.021
|
1.48 Liters
Standard Error 0.021
|
1.36 Liters
Standard Error 0.021
|
SECONDARY outcome
Timeframe: Day 1 (from 0 to 4 hours post morning dose)Population: The modified intent-to-treat (mITT) population, included all randomized patients who received at least one dose of study drug.
FEV1 was measured with spirometry conducted according to internationally accepted standards. The peak effect on Day 1 was defined as the maximum FEV1 during the first 4 hour on that day. FEV1 measurements taken within 6 hour of rescue use were set to missing before the peak FEV1 (0-4 hour) was calculated. The model used for analysis contained the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.
Outcome measures
| Measure |
Indacaterol 150 μg
n=118 Participants
Indacaterol 150 μg once daily delivered via SDDPI and placebo to tiotropium was delivered once daily via the tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
Indacaterol 300 μg
n=122 Participants
Indacaterol 300 μg once daily delivered via single dose dry powder inhaler (SDDPI)and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=120 Participants
Tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via single dose dry powder inhaler (SDDPI). Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
Placebo
n=121 Participants
Placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
|---|---|---|---|---|
|
Peak FEV1 During 4 Hours Post Morning Dose on Day 1
|
1.65 Liters
Standard Error 0.015
|
1.67 Liters
Standard Error 0.015
|
1.62 Liters
Standard Error 0.015
|
1.48 Liters
Standard Error 0.015
|
Adverse Events
Indacaterol 150 μg
Serious events: 2 serious events
Other events: 15 other events
Deaths: 0 deaths
Indacaterol 300 μg
Serious events: 1 serious events
Other events: 17 other events
Deaths: 0 deaths
Tiotropium 18 μg
Serious events: 4 serious events
Other events: 11 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Indacaterol 150 μg
n=118 participants at risk
Indacaterol 150 μg once daily delivered via single dose dry powder inhaler (SDDPI) and placebo to tiotropium was delivered once daily via the tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
Indacaterol 300 μg
n=122 participants at risk
Indacaterol 300 μg once daily delivered via single dose dry powder inhaler (SDDPI). Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=120 participants at risk
Tiotropium 18 μg once daily delivered via inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
Placebo
n=123 participants at risk
Placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
|---|---|---|---|---|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/118 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
0.00%
0/122 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
0.83%
1/120 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
0.00%
0/123 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.7%
2/118 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
0.82%
1/122 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
2.5%
3/120 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
0.81%
1/123 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/118 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
0.00%
0/122 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
1.7%
2/120 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
0.81%
1/123 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/118 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
0.00%
0/122 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
1.7%
2/120 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
0.81%
1/123 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
Other adverse events
| Measure |
Indacaterol 150 μg
n=118 participants at risk
Indacaterol 150 μg once daily delivered via single dose dry powder inhaler (SDDPI) and placebo to tiotropium was delivered once daily via the tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study.
|
Indacaterol 300 μg
n=122 participants at risk
Indacaterol 300 μg once daily delivered via single dose dry powder inhaler (SDDPI). Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
Tiotropium 18 μg
n=120 participants at risk
Tiotropium 18 μg once daily delivered via inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
Placebo
n=123 participants at risk
Placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study.
|
|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
3.4%
4/118 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
7.4%
9/122 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
4.2%
5/120 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
4.9%
6/123 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
3.4%
4/118 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
2.5%
3/122 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
5.8%
7/120 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
8.1%
10/123 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.8%
8/118 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
4.9%
6/122 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
0.83%
1/120 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
1.6%
2/123 • 10 weeks
In the safety population, all patients were analyzed according to treatment received.
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER