A multi-centre, randomized, double-blind, placebocontrolled, multiple-dose, 4-way cross-over study to evaluate the efficacy, safety, tolerability and pharmacokinetics of orally inhaled indacaterol salts (maleate, xinafoate and acetate) in patients with persistent asthma - ND

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-010589-46-IT
• Date of registration: 05/08/2009
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: A multi-centre, randomized, double-blind, placebocontrolled, multiple-dose, 4-way cross-over study to evaluate the efficacy, safety, tolerability and pharmacokinetics of orally inhaled indacaterol salts (maleate, xinafoate and acetate) in patients with persistent asthma - ND
• Scientific title: A multi-centre, randomized, double-blind, placebocontrolled, multiple-dose, 4-way cross-over study to evaluate the efficacy, safety, tolerability and pharmacokinetics of orally inhaled indacaterol salts (maleate, xinafoate and acetate) in patients with persistent asthma - ND
• Date of first enrolment: 19/05/2009
• Target sample size: 32
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010589-46
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: confronto tra i 3 diversi sali dell`indacaterolo

Countries of recruitment

France, Germany, Italy

Key inclusion & exclusion criteria

Inclusion criteria:
1) Non smoker male and female adult patients aged 18-75 years inclusive, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
2) Patients with asthma, diagnosed according to GINA guidelines (National Institute of Health, National Heart, Lung and Blood Institute, 2008) and who additionally meet the following criteria:
a. 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 screening.
b. Patients with an FEV1 at Visit 1 of ≥50% of the predicted normal value for the patient.
c. 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 MDI (or equivalent dose of DPI) (the reversibility test).
3) Women of child-bearing potential (WOCBP), unless they meet the definition of post-menopausal written in the Protocol OR have past 6 weeks from surgical bilateral oophorectomy OR are using one of the acceptable methods of contraception listed in the Protocol.
4) BMI must be within the range 18-32 kg/m2 (inclusive).
5) Vital signs not considered by the Investigator to be indicative of a disorder which would make it unsafe for subject to participate in the study or require medical intervention.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1) A urine cotinine level greater then the local laboratory lowest level of quantification.
2) Patients who have had previous intubation for a severe asthma attack/exacerbation.
3) Patients who have had a severe asthma attack/exacerbation requiring hospitalization in the 6 months prior to screening.
4) Patients who have had an emergency room visit for an asthma attack/exacerbation within 6 weeks prior to screening or any time between screening and per-dose day 1.
5) Patients who have had a respiratory tract infection within 4 weeks prior to screening or any time between screening and per-dose day 1.
6) Patients with seasonal allergy whose asthma is likely to deteriorate during the study period.
7) Patients who require the use of ≥8 inhalations per day of the short-acting β2-agonist on any 2 consecutive days from screening to randomization.
8) Patients diagnosed with COPD.
9) Patients with concomitant pulmonary disease, pulmonary tuberculosis or clinically significant bronchiectasis.
10) Any patient with lung cancer or a history of lung cancer.
11) Significant illness within the two weeks prior to dosing.
12) History of left-ventricular heart failure or symptomatic coronary atherosclerotic cardiovascular disease.
13) A past medical history of life-threatening arrhythmias or a history, or family history, of long QT syndrome.
14) Patients with a persistent systemic blood pressure ≥ 150/90 mmHg, measured on 2 separate occasions at least 24-hours apart.
15) Pregnant or nursing (lactating) women.
16) Patients with diabetes Type I or uncontrolled diabetes Type II.
17) Patients who have ever received or are currently receiving treatment with omalizumab.
18) Treatments for asthma and allied conditions with not allowed medicationslisted in the protocol prior to screening for at least the minimum period specified in the protocol or any time during the study.
19) The following treatments should not be used for the period specified in the protocol:
 antihistamines
 inhaled nasal cromolyn and inhaled nasal corticosteroids
 maintenance immuontherapy (desensitization) for allergies
 non-potassium-sparing diuretics
 β-adrenergic antagonists
 drugs with potential to significantly prolong the QT-interval
 tricyclic antidepressants and monoamine oxidase inhibitors
 anti-tussive medication
 opiates.
20) Patients unable to successfully use a dry powder inhaler device or perform spirometry measurements.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Persistent Asthma
MedDRA version: 12.0 Level: LLT Classification code 10003553 Term: Asthma

Intervention(s)

Product Name: indacaterol salts (maleate, xinafoate, acetate)
Product Code: QAB149
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: indacaterol salts (maleate, xinafoate, acetate)
Current Sponsor code: QAB149
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): Change from baseline to trough FEV1 after 7 days of treatment. Trough FEV1 is defined as the mean of the FEV1 measurements at 23 h 10 min and 23 h 45 min post dose.

Secondary Objective: - To assess the bronchodilator effect of orally inhaled indacaterol salts in patients with persistent asthma compared with placebo
- Morning and evening PEF measurements for indacaterol salts in comparison to placebo
- To assess day and night rescue medication usage for indacaterol salts in comparison to placebo
- To assess the safety and tolerability of indacaterol salts in comparison to placebo in terms of the number and percentage of adverse events, laboratory analysis, vital signs (blood pressure and pulse rate) and ECGs
- To evaluate the incidence of post-inhalational cough and tolerability, as determined by the investigator and the patient, after administration of indacaterol salts in comparison to placebo
- To assess the pharmacokinetics of indacaterol after 7 days of treatment of orally inhaled indacaterol salts (maleate, xinafoate and acetate) in patients with persistent asthma

Main Objective: To assess the bronchodilator effect of orally inhaled indacaterol salts (maleate, xinafoate and acetate) in patients with persistent asthma compared with placebo as measured by mean change in FEV1 from baseline to post-dose trough after 7 days of treatment. Trough is defined as the mean of FEV1 at 23 h 10 min and 23 h 45 min post-dose.

Secondary ID(s)

2009-010589-46-DE

CQAB149D2301