Clinical trial NCT00545272: A Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via TWISTHALER® Device in Adult and Adolescent Patients With Persistent Asthma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: QMF
indacaterol
Twisthaler®
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Schering-Plough
First posted: 2007-10-17
Enrollment: 392
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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 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

Primary outcomes:
measure: The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline (prior to first dose) and Day 15 (24 hours after last dose)
Secondary outcomes:
measure: Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose
timeFrame: Day 14, pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose.
measure: The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) on Day 1
timeFrame: Day 1 Baseline (prior to first dose) and 24 hours post-dose.
measure: Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose on Day 1
timeFrame: Day 1, pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose.
measure: Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 14
timeFrame: Day 1 and Day 14 measured pre-dose and up to 4 hours post-dose
measure: Change From Baseline in Morning and Evening Peak Expiratory Flow
timeFrame: Baseline (recorded during the screening period) and Days 1-14 (treatment period)
measure: Number of Participants Using Rescue Medication
timeFrame: Over 14 days
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: Novartis Investigator Site
city: Halen
country: Belgium
facility: Novartis Investigator Site
city: Oostham
country: Belgium
facility: Novartis Investigator Site
city: Veurne
country: Belgium
facility: Novartis Investigator site
city: Boskovice
country: Czech Republic
facility: Novartis Investigator Site
city: Breclav
country: Czech Republic
facility: Novartis Investigator site
city: Brno
country: Czech Republic
facility: Novartis Investigator Site
city: Liberec
country: Czech Republic
facility: Novartis Investigator Site
city: Most
country: Czech Republic
facility: Novartis Investigator Site
city: Tabor
country: Czech Republic
facility: Novartis Investigator Site
city: Aalen
country: Germany
facility: Novartis Investigator Site
city: Berlin
country: Germany
facility: Novartis Investigator Site
city: Braunschweig
country: Germany
facility: Novartis Investigator Site
city: Deggendorf
country: Germany
facility: Novartis Investigator Site
city: Furstenwalde
country: Germany
facility: Novartis Investigator Site
city: Leipzig
country: Germany
facility: Novartis Investigator Site
city: Munchen
country: Germany
facility: novartis Investigator site
city: Balassagyarmat
country: Hungary
facility: Novartis investigator site
city: Erd
country: Hungary
facility: Novartis Investigator Site
city: Fuzesabony
country: Hungary
facility: Novartis Investigator site
city: Gyonggyos
country: Hungary
facility: Novartis Investigator Site
city: Mosdoz
country: Hungary
facility: Novartis Investigator Site
city: Pest
country: Hungary
facility: Novartis Investigator Site
city: Siofok
country: Hungary
facility: Novartis Investigator Site
city: Szazhalombatta
country: Hungary
facility: Novartis Investigator Site
city: Afula
country: Israel
facility: Novartis Investigator Site
city: Ashkelon
country: Israel
facility: Novartis Investigator Site
city: Beer Sheva
country: Israel
facility: Novartis Investigator Site
city: Haifa
country: Israel
facility: Novartis investigator site
city: Jerusalem
country: Israel
facility: Novartis investigator site
city: Petach Tikva
country: Israel
facility: Novartis Investigator Site
city: Rehovot
country: Israel
facility: Novartis Investigator Site
city: Tel Aviv
country: Israel
facility: Novartis Investigator Site
city: Tel-Hashorner
country: Israel
facility: Novartis Investigator Site
city: Zrifin
country: Israel
facility: Novartis Investigator Site
city: Bialystok
country: Poland
facility: Novartis Investigator Site
city: Bydgoszcz
country: Poland
facility: Novartis investigator site
city: Lodz
country: Poland
facility: Novartis Investigator Site
city: Lubin
country: Poland
facility: Novartis Investigator site
city: Tarnow
country: Poland
facility: Novartis Investigator Site
city: Moscow
country: Russian Federation
facility: Novartis Investigator Site
city: Saint-Petersburg
country: Russian Federation
facility: Novartis Investigator Site
city: Smolensk
country: Russian Federation
facility: Novartis Investigator Site
city: Tomsk
country: Russian Federation
facility: Novartis investigator site
city: Bloernfontain
country: South Africa
facility: Novartis Investigator Site
city: Cape Town
country: South Africa
facility: Novartis Investigator Site
city: Johannesburg
country: South Africa
facility: Novartis Investigator Site
city: Krugersdorp
country: South Africa
facility: Novartis Investigator Site
city: les Marais
country: South Africa
facility: Novartis Investigator Site
city: Pretoria
country: South Africa
facility: Novartis Investigator Site
city: Roodepoort
country: South Africa
facility: Novartis Investigator Site
city: Temba
country: South Africa
facility: Novartis Investigator Site
city: Madrid
country: Spain
facility: Novartis Investigator Site
city: Pozuelo de Alacron
country: Spain
facility: Novartis Investigator Site
city: Valencia
country: Spain
facility: Novartis Investigator Site
city: Downpatrick
country: United Kingdom
facility: Novartis Investigator Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigator Site
city: London
country: United Kingdom
facility: Novartis Investigator Site
city: Southampton
country: United Kingdom
facility: Novartis Investigator Site
city: Watford
country: United Kingdom
facility: Novartis Investigator Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharma
role: STUDY_CHAIR
References: