A randomized, double-blind, controlled, parallel group, 12-week treatment study to compare the efficacy and safety of the combination of indacaterol 150 µg once daily with open label tiotropium 18 µg once daily versus open label tiotropium 18 µg once daily in patients with moderate to severe chronic obstructive pulmonary disease - INTRUST 1

• Register: EUCTR
• Last refreshed on: 25 February 2013
• Main ID: EUCTR2008-006976-31-DE
• Date of registration: 29/01/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized, double-blind, controlled, parallel group, 12-week treatment study to compare the efficacy and safety of the combination of indacaterol 150 µg once daily with open label tiotropium 18 µg once daily versus open label tiotropium 18 µg once daily in patients with moderate to severe chronic obstructive pulmonary disease - INTRUST 1
• Scientific title: A randomized, double-blind, controlled, parallel group, 12-week treatment study to compare the efficacy and safety of the combination of indacaterol 150 µg once daily with open label tiotropium 18 µg once daily versus open label tiotropium 18 µg once daily in patients with moderate to severe chronic obstructive pulmonary disease - INTRUST 1
• Target sample size: 1126
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-006976-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Both arms receive open label tiotropium in combination with blinded indacaterol or placebo. If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Denmark, Germany, Greece, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1.Male and female adults aged 40 years and over, who have signed an ICF prior to initiation of any study-related activities
2.Co-operative outpatients with a diagnosis of COPD (moderate to severe as classified by the GOLD Guidelines, 2007, Appendix 2) and including:
a)Smoking history of at least 10 pack years, both current and ex-smokers are eligible
b)Post-bronchodilator FEV1 =65% and = 30% of the predicted normal value (Visit 2)
c)Post-bronchodilator FEV1/FVC < 70% (Visit 2)
(Post refers to 10-15 min after inhalation of 400 µg (4x100µg) of salbutamol, equivalent to 4x90 µg albuterol delivered at the mouthpiece, at Visit 2).

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.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotrophin laboratory test (>5 mIU/mL)
2.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels >40 mIU/mL or are using one or more of the acceptable methods of contraception.
3.Patients with body mass index (BMI) less than 15 or more than 40 kg/m2
4.Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment or antibiotics and/or hospitalization in the 6 weeks prior to screening (Visit 2). In the event of an exacerbation occurring during the run-in period (Visits 2-4), the patient must discontinue from the study. The patient may be re-screened once the inclusion/exclusion criteria have been met
5.Patients requiring oxygen therapy for chronic hypoxemia (excluding acute COPD exacerbation). This is typically patients requiring oxygen therapy >15 h per day delivered by home oxygen cylinder or concentrator
6.Patients who have had a respiratory tract infection within 6 weeks prior to Visit 2. Patients who develop a respiratory tract infection between Visit 2 and Visit 4 must discontinue from the trial, but may be re-screened at a later date once the inclusion/exclusion criteria have been met
7.Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active), or clinically significant bronchiectasis
8.Patients with a history (up to and including Visit 2) of asthma indicated by (but not limited to):
a) onset of respiratory symptoms (such as cough, wheezing, shortness of breath) suggestive of asthma prior to age 40 years
b) history of a diagnosis of asthma
9.Patients with diabetes Type I or uncontrolled diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range or HbA1c > 8.0 % of total hemoglobin measured at Visit 2
10.Patients with contraindications for tiotropium treatment including medical history of symptomatic prostatic hypertrophy, bladder neck obstruction, narrow angle glaucoma and moderate to severe renal impairment (creatinine clearance = 50 mL/min)
11.Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) unstable ischemic heart disease, arrhythmia (excluding chronic stable atrial fibrillation) or other clinically significant ECG findings, uncontrolled hypertension and other significant cardiac disease or conduction defect, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state or any condition which in the opinion of investigator or Novartis responsible personnel might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study
12.Patients with lung cancer or a history of lung cancer
13.Patients with active malignancy or a history of malignancy of any organ system (oth

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

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 9.1 Level: LLT Classification code 10010952 Term: COPD

Intervention(s)

Product Name: Indacaterol
Product Code: QAB149
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Indacaterol
Current Sponsor code: QAB149
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Trade Name: Spiriva 10 Mikrogramm (via HandiHaler)
Product Name: Spiriva 18 Mikrogramm (via HandiHaler)
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Tiotropium
CAS Number: 139404-48-1
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 18-

Primary Outcome(s)

Main Objective: To demonstrate superiority of indacaterol 150 µg o.d. in combination with tiotropium 18 µg o.d. versus tiotropium 18 µg o.d. with respect to standardized AUC for FEV1 between 5 min – 8 h post-dose after 12 weeks of treatment in patients with moderate to severe COPD.

Primary end point(s): To demonstrate superiority of indacaterol 150 µg o.d. in combination with tiotropium 18 µg o.d. versus tiotropium 18 µg o.d. with respect to standardized AUC for FEV1 between 5 min – 8 h post-dose after 12 weeks of treatment in patients with moderate to severe COPD.

Secondary Objective: To demonstrate superiority of indacaterol 150 µg o.d. in combination with tiotropium 18 µg o.d versus tiotropium 18 µg o.d with respect to trough FEV1 24h post-dose after 12 weeks of treatment in patients with moderate to severe COPD.
The 24 h post-dose trough FEV1 is defined as the mean of FEV1 measurements at 23 h 10 min and 23 h 45 min post-dose.

Secondary ID(s)

CQAB149B2341

2008-006976-31-DK