A Dose Ranging Trial of 4 Doses of Indacaterol Delivered... | NCT00545272

NCT00545272

ID	Type	Description	Link
2007-003191-19	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
Schering-Plough	INDUSTRY

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
indacaterol 62.5 μg	Experimental	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. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.	Drug: indacaterol Drug: placebo to formoterol Drug: short acting β2-agonist
indacaterol 125 μg	Experimental	Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.	Drug: indacaterol Drug: placebo to formoterol Drug: short acting β2-agonist
indacaterol 250 μg	Experimental	Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.	Drug: indacaterol Drug: placebo to formoterol Drug: short acting β2-agonist
indacaterol 500 μg	Experimental	Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
indacaterol	Drug	Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).	indacaterol 125 μg indacaterol 250 μg indacaterol 500 μg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)	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.	Baseline (prior to first dose) and Day 15 (24 hours after last dose)

Secondary Outcomes

Measure	Description	Time Frame
Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose	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.	Day 14, pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and female adult and adolescent patients aged 12-75 years inclusive (or ≥18-75 years depending upon regulatory and/or Institutional Review Board (IRB)/Independent Ethics Committee (IEC)/Research Ethics Board (REB) approval), who have signed an Informed Consent Form prior to initiation of any study-related procedure, including any adjustments to asthma medication prior to Visit 1. Patients below the legal age of consent are required to have the Informed Consent Form signed by the patient's parent / guardian.
Patients with asthma, diagnosed according to Global Initiative for Asthma (GINA) guidelines (National Institute of Health, National Heart, Lung and Blood Institute, 2006) and who additionally meet the following criteria:
1. Patients receiving daily treatment with inhaled corticosteroid up to the maximum dose per day indicated in the package leaflet, in a stable regimen for the month prior to Visit 1.
2. Patients with a Forced Expiratory Volume in one second (FEV1) at Visit 1 of ≥50% of the predicted normal value for the patient. This criterion for FEV1 will have to be demonstrated after a washout period of at least 6 hours during which no short acting β2-agonist has been inhaled, and a minimum of 48 hours for a long acting β2-agonist.
3. Patients who demonstrate an increase of ≥12% and ≥200 mL in FEV1 over their pre-bronchodilator value within 30 minutes after inhaling a total of 200 µg/180 µg of salbutamol/albuterol Metered Dose Inhaler (MDI) (or equivalent dose of Dry Powder Inhaler [DPI]) (the reversibility test). Reversibility will have to be demonstrated after an appropriate washout period of at least 6 hrs prior to the evaluation for a short-acting β2-agonist. The administration of salbutamol/albuterol for the reversibility test is to be within 30 minutes after pre bronchodilator spirometry. Reversibility has to be demonstrated at Visit 1 or between Visits 1 and 2, in order for patients to be included in the trial.

Exclusion Criteria:

Pregnant women, nursing mothers, or females of childbearing potential, regardless of whether or not sexually active, if they are not using a reliable form of contraception.
Patients with Chronic Obstructive Pulmonary Disease (COPD), or current smokers, or patients who have used tobacco products within the 6 month period prior to Visit 1, or who have a smoking history of greater than 10 pack years.
Patients:
1. who's asthma is likely to deteriorate during the study (including seasonal allergy),
2. hospitalized for an acute asthma attack/asthma exacerbation within 6 months prior to Visit 1,
3. who have had an emergency room visit for an asthma attack/asthma exacerbation within 6 weeks prior to Visit 1
4. who have had a respiratory tract infection or emergency room treatment for an asthma attack/asthma exacerbation within 4 weeks prior to Visit 1
5. Patients who require the use of ≥8 inhalations per day of short acting B2-agonist (100 µg/ 90 µg salbutamol/albuterol MDI or equivalent dose of DPI) on any 2 consecutive days from Screening to Randomization.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharma	Novartis Pharmaceuticals	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigator Site		Aalst			Belgium
Novartis Investigator Site

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	Indacaterol 125 μg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

indacaterol 62.5 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.

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	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.
BG004	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.
BG005	Placebo	Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.
BG006	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0000.039± 0.0408 OG0010.054± 0.0383 OG0020.124± 0.0401 OG003

Secondary

Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose

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.

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.

Posted

Least Squares Mean

Standard Error

liters

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) on Day 1

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.

Posted

Least Squares Mean

Standard Error

liters

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose on Day 1

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.

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.

Posted

Least Squares Mean

Standard Error

liters

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 14

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.

Posted

Mean

Standard Deviation

minutes

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Change From Baseline in Morning and Evening Peak Expiratory Flow

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.

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

Posted

Mean

Standard Deviation

liters/minute

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

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Number of Participants Using Rescue Medication

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.

Intent to treat

Posted

Number

participants

Over 14 days

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	0	61	2	61
EG001	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.	0	68	2	68
EG002	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.	0	65	4	65
EG003	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.	0	72	8	72
EG004	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.	0	64	0	64
EG005	Placebo	Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days.	1	62	1	62

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Asthmatic crisis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment		EG0000 affected61 at risk EG0010 affected68 at risk EG0020 affected65 at risk EG0030 affected72 at risk EG004

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment		EG0002 affected61 at risk EG0012 affected68 at risk EG0024 affected65 at risk EG0038 affected72 at risk EG0040 affected64 at risk EG0051 affected62 at risk

ID	Term
D001249	Asthma

Ancestor Terms

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Term
C510790	indacaterol
D000068759	Formoterol Fumarate

OG005-0.018± 0.0415

EG0051 affected62 at risk

ID	Term
D004983	Ethanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D000588	Amines