Trial Outcomes & Findings for A Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via TWISTHALER® Device in Adult and Adolescent Patients With Persistent Asthma (NCT NCT00545272)

Results Overview

FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from baseline to 24 hour post dose trough FEV1 after 14 days of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

392 participants

Primary outcome timeframe

Baseline (prior to first dose) and Day 15 (24 hours after last dose)

Results posted on

2013-01-18

Participant Flow

Participant milestones

Participant milestones
Measure	Indacaterol 62.5 μg Indacaterol 62.5 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 125 μg Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 250 μg Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 500 μg Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Formoterol Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days.	Placebo Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.
Overall Study STARTED	61	68	65	72	64	62
Overall Study COMPLETED	61	67	64	71	62	59
Overall Study NOT COMPLETED	0	1	1	1	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Indacaterol 125 μg Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 250 μg Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 500 μg Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Formoterol Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days.	Placebo Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.
Overall Study Protocol deviation	1	0	1	0	1
Overall Study Adverse Event	0	1	0	0	1
Overall Study Abnormal laboratory value(s)	0	0	0	0	1
Overall Study Abnormal test procedure result(s)	0	0	0	1	0
Overall Study Lost to Follow-up	0	0	0	1	0

Baseline Characteristics

A Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via TWISTHALER® Device in Adult and Adolescent Patients With Persistent Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Indacaterol 62.5 μg n=61 Participants Indacaterol 62.5 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 125 μg n=68 Participants Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 250 μg n=65 Participants Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 500 μg n=72 Participants Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Formoterol n=64 Participants Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days.	Placebo n=62 Participants Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Total n=392 Participants Total of all reporting groups
Age Continuous	41.3 years STANDARD_DEVIATION 16.27 • n=5 Participants	38.4 years STANDARD_DEVIATION 17.25 • n=7 Participants	36.6 years STANDARD_DEVIATION 15.76 • n=5 Participants	40.1 years STANDARD_DEVIATION 15.47 • n=4 Participants	44.0 years STANDARD_DEVIATION 17.98 • n=21 Participants	39.8 years STANDARD_DEVIATION 15.82 • n=8 Participants	40.0 years STANDARD_DEVIATION 16.50 • n=8 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	37 Participants n=7 Participants	36 Participants n=5 Participants	39 Participants n=4 Participants	27 Participants n=21 Participants	37 Participants n=8 Participants	204 Participants n=8 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	31 Participants n=7 Participants	29 Participants n=5 Participants	33 Participants n=4 Participants	37 Participants n=21 Participants	25 Participants n=8 Participants	188 Participants n=8 Participants

PRIMARY outcome

Timeframe: Baseline (prior to first dose) and Day 15 (24 hours after last dose)

Population: The intent-to-treat population (ITT) population consisted of all randomized patients who had a baseline and at least one post-dose FEV1 measurement. The analysis only includes patients with non-missing data.

FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from baseline to 24 hour post dose trough FEV1 after 14 days of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate.

Outcome measures

Outcome measures
Measure	Indacaterol 62.5 μg n=60 Participants Indacaterol 62.5 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 125 μg n=67 Participants Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 250 μg n=63 Participants Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 500 μg n=68 Participants Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Formoterol n=62 Participants Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days.	Placebo n=58 Participants Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.
The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)	0.039 liters Standard Error 0.0408	0.054 liters Standard Error 0.0383	0.124 liters Standard Error 0.0401	0.166 liters Standard Error 0.0381	0.075 liters Standard Error 0.0405	-0.018 liters Standard Error 0.0415

SECONDARY outcome

Timeframe: Day 14, pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose.

Population: The intent-to-treat population (ITT) population consisted of all randomized patients who had a baseline and at least one post-dose FEV1 measurement. Observed data only.

FEV1 was measured on Day 14 pre-dose and up to 4 hours post-dose. The Area Under the Curve (AUC) for FEV1 was analyzed using Analysis of Covariance adjusting for treatment and region with baseline FEV1 as a covariate.

Outcome measures

Outcome measures
Measure	Indacaterol 62.5 μg n=61 Participants Indacaterol 62.5 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 125 μg n=66 Participants Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 250 μg n=64 Participants Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 500 μg n=69 Participants Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Formoterol n=62 Participants Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days.	Placebo n=59 Participants Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.
Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose	2.670 liters Standard Error 0.0419	2.698 liters Standard Error 0.0400	2.772 liters Standard Error 0.0411	2.786 liters Standard Error 0.0393	2.821 liters Standard Error 0.0418	2.565 liters Standard Error 0.0426

SECONDARY outcome

Timeframe: Day 1 Baseline (prior to first dose) and 24 hours post-dose.

Population: The intent-to-treat population (ITT) population consisted of all randomized patients who had a baseline and at least one post-dose FEV1 measurement. The analysis only includes patients with non-missing data.

FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from baseline to 24 hour post dose trough FEV1 after 1 day of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate.

Outcome measures

Outcome measures
Measure	Indacaterol 62.5 μg n=61 Participants Indacaterol 62.5 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 125 μg n=68 Participants Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 250 μg n=64 Participants Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 500 μg n=69 Participants Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Formoterol n=63 Participants Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days.	Placebo n=62 Participants Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.
The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) on Day 1	0.054 liters Standard Error 0.0347	0.081 liters Standard Error 0.0326	0.143 liters Standard Error 0.0339	0.141 liters Standard Error 0.0326	0.155 liters Standard Error 0.0341	0.010 liters Standard Error 0.0344

SECONDARY outcome

Timeframe: Day 1, pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose.

Population: The intent-to-treat population (ITT) population consisted of all randomized patients who had a baseline and at least one post-dose FEV1 measurement. Observed data only.

FEV1 was measured on Day 1 pre-dose and up to 4 hours post-dose. The Area Under the Curve (AUC) for FEV1 was analyzed using Analysis of Covariance adjusting for treatment and region with baseline FEV1 as a covariate.

Outcome measures

Outcome measures
Measure	Indacaterol 62.5 μg n=61 Participants Indacaterol 62.5 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 125 μg n=68 Participants Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 250 μg n=65 Participants Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 500 μg n=71 Participants Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Formoterol n=64 Participants Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days.	Placebo n=62 Participants Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.
Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose on Day 1	2.668 liters Standard Error 0.0281	2.687 liters Standard Error 0.0264	2.726 liters Standard Error 0.0272	2.753 liters Standard Error 0.0259	2.832 liters Standard Error 0.0274	2.547 liters Standard Error 0.0279

SECONDARY outcome

Timeframe: Day 1 and Day 14 measured pre-dose and up to 4 hours post-dose

Population: The intent-to-treat population (ITT) population consisted of all randomized patients who had a baseline and at least one post-dose FEV1 measurement. The analysis only includes patients with non-missing data, indicated by "N".

FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Time to peak FEV1 is calculated in minutes from the time of inhalation of study drug to the time of the peak FEV1, which is taken as the maximum FEV1 recorded post-dose.

Outcome measures

Outcome measures
Measure	Indacaterol 62.5 μg n=61 Participants Indacaterol 62.5 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 125 μg n=68 Participants Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 250 μg n=65 Participants Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 500 μg n=72 Participants Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Formoterol n=64 Participants Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days.	Placebo n=62 Participants Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.
Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 14 Day 14 [N=61, 66, 64, 70, 62, 59]	103.8 minutes Standard Deviation 86.67	118.7 minutes Standard Deviation 88.42	96.7 minutes Standard Deviation 70.65	114.0 minutes Standard Deviation 76.41	114.6 minutes Standard Deviation 71.64	80.4 minutes Standard Deviation 76.92
Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 14 Day 1 [N=61, 68, 65, 71, 64, 62]	91.0 minutes Standard Deviation 83.02	109.6 minutes Standard Deviation 81.09	119.0 minutes Standard Deviation 81.64	116.2 minutes Standard Deviation 75.50	105.6 minutes Standard Deviation 70.64	90.5 minutes Standard Deviation 82.46

SECONDARY outcome

Timeframe: Baseline (recorded during the screening period) and Days 1-14 (treatment period)

Population: Intent to treat population. The analysis only includes patients with non-missing data, indicated by "N".

The Peak Expiratory Flow (PEF) rate is the maximal rate that a person can exhale during a short maximal expiratory effort after fully inhaling. Participants measured their PEF using a peak flow meter and recorded measurements in a diary every morning and evening during the study, prior to taking study medication. Change from baseline is the difference between the mean baseline PEF recorded during the screening period until the first day of treatment, and the overall mean PEF from Days 1 to 14.

Outcome measures

Outcome measures
Measure	Indacaterol 62.5 μg n=61 Participants Indacaterol 62.5 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 125 μg n=68 Participants Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 250 μg n=65 Participants Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Indacaterol 500 μg n=72 Participants Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	Formoterol n=64 Participants Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days.	Placebo n=62 Participants Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.
Change From Baseline in Morning and Evening Peak Expiratory Flow Morning [N=56, 61, 53, 63, 57, 48]	18.7 liters/minute Standard Deviation 29.28	17.2 liters/minute Standard Deviation 34.07	25.7 liters/minute Standard Deviation 38.37	25.8 liters/minute Standard Deviation 47.36	25.2 liters/minute Standard Deviation 38.28	-4.3 liters/minute Standard Deviation 43.00
Change From Baseline in Morning and Evening Peak Expiratory Flow Evening [N=56, 58, 54, 59, 55, 47]	5.9 liters/minute Standard Deviation 36.92	4.2 liters/minute Standard Deviation 37.82	18.4 liters/minute Standard Deviation 36.70	25.8 liters/minute Standard Deviation 38.07	26.2 liters/minute Standard Deviation 35.01	-11.4 liters/minute Standard Deviation 50.73

SECONDARY outcome

Timeframe: Over 14 days

Population: Intent to treat

Participants recorded the use of rescue medications (salbutamol/albuterol) for treatment of asthma symptoms twice a day in a diary during the 14 days of the treatment period.