A 12 week treatment, multi-center, randomized, parallel group, double blind, double dummy study to assess the superiority of indacaterol (150 µg o.d.) via a SDDPI in patients with moderate to severe COPD, using salmeterol (50 µg b.i.d.) as an active comparator delivered via a DISKUS inhaler. - INSIST

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-005146-23-CZ
• Date of registration: 26/01/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 12 week treatment, multi-center, randomized, parallel group, double blind, double dummy study to assess the superiority of indacaterol (150 µg o.d.) via a SDDPI in patients with moderate to severe COPD, using salmeterol (50 µg b.i.d.) as an active comparator delivered via a DISKUS inhaler. - INSIST
• Scientific title: A 12 week treatment, multi-center, randomized, parallel group, double blind, double dummy study to assess the superiority of indacaterol (150 µg o.d.) via a SDDPI in patients with moderate to severe COPD, using salmeterol (50 µg b.i.d.) as an active comparator delivered via a DISKUS inhaler. - INSIST
• Date of first enrolment: 17/03/2009
• Target sample size: 1084
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005146-23
• 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: Double dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Czech Republic, Germany, Hungary, Slovakia, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
Male and female adults aged =40 years, who have signed an Informed Consent form prior
to initiation of any study-related procedure;
2. Co-operative outpatients with a diagnosis of COPD (moderate to severe as classified by
the GOLD Guidelines, 2007, Appendix 2) and additionally including:
• Smoking history of at least 10 pack years
• Post-bronchodilator FEV1 <80% and =30% of the predicted normal value at
screening (Visit 2).
• Post-bronchodilator FEV1/FVC < 70% at screening (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 postmenopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/mL or are using one or more of the acceptable methods of contraception define in the protocol.
3. Acceptable methods of contraception may include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation;
4. Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid
treatment or antibiotics and/or hospitalization in the 6 weeks prior to screening. In the event of an exacerbation occurring during the run-in period, the patient must discontinue from the study. The patient may re-enroll once the inclusion/exclusion criteria have been met
5. Patients whose body mass index is less than 15 or greater than 40 kg/m2;
6. 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
7. Patients who have had a respiratory tract infection within 6 weeks prior to screening. Patients who develop a respiratory tract infection between prescreening and randomizationmust discontinue from the trial, but may be permitted to re-enroll at a later date once the inclusion/exclusion criteria have been met
8. Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis
9. Patients with a history of asthma indicated
10. 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 Hb measured at screening
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 the investigator or Novartis responsible personnel might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study
12. Any patient with lung cancer or a history of lung cancer
13. Any patient with active cancer or a history of cancer with less than 5 ye

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

Health Condition(s) or Problem(s) studied

COPD (chronic obstructive pulmonary disease)
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
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: Serevent Diskus
Product Name: Salmeterol admisistered by DISKUS inhlaler
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Salmeterol
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: To demonstrate the superiority of indacaterol (150 µg o.d.) versus salmeterol (50 µg b.i.d.) with respect to standardized area under the curve (AUC) for forced expiratory volume in one second (FEV1) between 5 min and 11 h 45 min after the morning dose on day 84 of treatment in patients with moderate to severe COPD.

Primary end point(s): To demonstrate superiority of indacaterol (150 µg o.d.) versus salmeterol (50 µg b.i.d.) in respect to standardized area under the curve (AUC) for forced expiratory volume (FEV1) between 5 min and 11 h 45 min after the morning doses after 84 days treatment in patients with moderate to severe COPD.

Secondary Objective: To demonstrate the superiority of indacaterol (150 µg o.d.) versus salmeterol (50 µg b.i.d.) with respect to trough FEV1 after 84 days of treatment in both arms: Trough refers to the mean of FEV1 at 23:10 and 23:45h after the morning dose of indacaterol, and the mean of FEV1 at 11:10 and 11:45h after the anticipated time of the evening dose of salmeterol.
To compare spirometry for indacaterol (150 µg o.d.) with salmeterol (50 µg b.i.d.).
To evaluate the effect of indacaterol 150 µg o.d. compared with salmeterol 50 µg b.i.d. in respect to TDI focal score on Day 84.
To compare the relative safety of indacaterol (150 µg o.d.) versus salmeterol (50 µg b.i.d) with respect to ECGs, laboratory tests, blood pressure, heart rate, and adverse events.

Secondary ID(s)

2008-005146-23-ES

CQAB149B2349