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

Asthma Clinical Trial

Official title:

A Randomized, Multi-center, Parallel Group, Double Blind, Placebo and Formoterol Controlled 14 Day Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via TWISTHALER® Device in Adult and Adolescent Patients With Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00545272
• Other study ID #: CQMF149A2201
• Secondary ID: 2007-003191-19
• Status: Completed
• Phase: Phase 2
• First received: October 16, 2007
• Last updated: December 12, 2012
• Start date: October 2007
• Est. completion date: April 2008

Study information

• Verified date: November 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsCzech Republic: State Institute for Drug ControlGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyIsrael: Ministry of HealthPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Ministry of Health of the Russian FederationSpain: Spanish Agency of MedicinesSouth Africa: Medicines Control CouncilUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the dose response relationship among four doses of indacaterol as well as placebo delivered via the TWISTHALER® device.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 392
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 75 Years

Eligibility

Inclusion Criteria:

1. 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.

2. 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 ß2-agonist has been inhaled, and a minimum of 48 hours for a long acting ß2-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 ß2-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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• indacaterol
Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).
• formoterol
Formoterol delivered by oral inhalation via AEROLIZER® inhalation device.
• placebo to indacaterol
Placebo TWISTHALER® device
• placebo to formoterol
Placebo AEROLIZER® device
• short acting ß2-agonist
100 µg/ 90 µg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).

Locations

Country	Name	City	State
Belgium	Novartis Investigator Site	Aalst
Belgium	Novartis Investigator Site	Halen
Belgium	Novartis Investigator Site	Oostham
Belgium	Novartis Investigator site	Veurne
Czech Republic	Novartis Investigator Site	Boskovice
Czech Republic	Novartis Investigator site	Breclav
Czech Republic	Novartis Investigator Site	Brno
Czech Republic	Novartis Investigator Site	Liberec
Czech Republic	Novartis Investigator Site	Most
Czech Republic	Novartis Investigator Site	Tabor
Germany	Novartis Investigator Site	Aalen
Germany	Novartis Investigator Site	Berlin
Germany	Novartis Investigator Site	Braunschweig
Germany	Novartis Investigator Site	Deggendorf
Germany	Novartis Investigator Site	Furstenwalde
Germany	Novartis Investigator Site	Leipzig
Germany	novartis Investigator site	Munchen
Hungary	Novartis investigator site	Balassagyarmat
Hungary	Novartis Investigator Site	Erd
Hungary	Novartis Investigator site	Fuzesabony
Hungary	Novartis Investigator Site	Gyonggyos
Hungary	Novartis Investigator Site	Mosdoz
Hungary	Novartis Investigator Site	Pest
Hungary	Novartis Investigator Site	Siofok
Hungary	Novartis Investigator Site	Szazhalombatta
Israel	Novartis Investigator Site	Afula
Israel	Novartis Investigator Site	Ashkelon
Israel	Novartis Investigator Site	Beer Sheva
Israel	Novartis investigator site	Haifa
Israel	Novartis investigator site	Jerusalem
Israel	Novartis Investigator Site	Petach Tikva
Israel	Novartis Investigator Site	Rehovot
Israel	Novartis Investigator Site	Tel Aviv
Israel	Novartis Investigator Site	Tel-Hashorner
Israel	Novartis Investigator Site	Zrifin
Poland	Novartis Investigator Site	Bialystok
Poland	Novartis investigator site	Bydgoszcz
Poland	Novartis Investigator Site	Lodz
Poland	Novartis Investigator site	Lubin
Poland	Novartis Investigator Site	Tarnow
Russian Federation	Novartis Investigator Site	Moscow
Russian Federation	Novartis Investigator Site	Saint-Petersburg
Russian Federation	Novartis Investigator Site	Smolensk
Russian Federation	Novartis investigator site	Tomsk
South Africa	Novartis Investigator Site	Bloernfontain
South Africa	Novartis Investigator Site	Cape Town
South Africa	Novartis Investigator Site	Johannesburg
South Africa	Novartis Investigator Site	Krugersdorp
South Africa	Novartis Investigator Site	les Marais
South Africa	Novartis Investigator Site	Pretoria
South Africa	Novartis Investigator Site	Roodepoort
South Africa	Novartis Investigator Site	Temba
Spain	Novartis Investigator Site	Madrid
Spain	Novartis Investigator Site	Pozuelo de Alacron
Spain	Novartis Investigator Site	Valencia
United Kingdom	Novartis Investigator Site	Downpatrick
United Kingdom	Novartis Investigator Site	Glasgow
United Kingdom	Novartis Investigator Site	London
United Kingdom	Novartis Investigator Site	Southampton
United Kingdom	Novartis Investigator Site	Watford

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Schering-Plough

Countries where clinical trial is conducted

Belgium,  Czech Republic,  Germany,  Hungary,  Israel,  Poland,  Russian Federation,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
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.	Day 14, pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose.	No
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.	Day 1 Baseline (prior to first dose) and 24 hours post-dose.	No
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.	Day 1, pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose.	No
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.	Day 1 and Day 14 measured pre-dose and up to 4 hours post-dose	No
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.	Baseline (recorded during the screening period) and Days 1-14 (treatment period)	No
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.	Over 14 days	No