Efficacy and Safety of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) Using Salmeterol as Active Control

Phase 3

Completed

• Conditions: Chronic Obstructive Pulmonary Disease (COPD)

• Registration Number: CTRI/2009/091/000260
• Lead Sponsor: Novartis Health care Private Limited

Brief Summary

26-week treatment, multi center, randomized, double blind, double dummy, placeboxml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /

controlled, parallel group study to assess the efficacy and safety of indacaterol (150 μg o.d.) in

patients with chronic obstructive pulmonary disease, using salmeterol (50 μg b.i.d.) as an active

control. The study population will consist of approximately 972 adult males and females from 16 different countries and age 40 years and over with a clinical diagnosis of moderate to severe COPD and a smoking history of at least 20 pack years. Patients will randomized into the study with the intention that at least 777 patients complete the study.  Primary objective is to assess indacaterol (150 μg) superiority in patients with COPD as compared to placebo with respect to 24 h post dose trough FEV1 after 12 weeks of treatment. Number of patients from India is 131.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11-01
• Last Update Posted: 2014-03-10

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 972

Inclusion Criteria

• 1.Male and female adults aged greater than or equal to 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, 2006) and including: a) Smoking history of at least 20 pack years b) Post-bronchodilator FEV1 less than 80 percent and greater than or equal to 30 percent of the predicted normal value c) Post-bronchodilator FEV1 FVC less than 70 percent.

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 fhuman chorionic gonadotrophin laboratory test (greater than 5 mIU per 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 greater than40 mIU per mL or are using one or more of the following acceptable methods of contraception. a) surgical sterilization (e.g. bilateral tubal ligation, hysterectomy) b) hormonal contraception (implantable, patch, oral) c) double-barrier methods (any double combination of. IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap) 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, post-ovulation 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 3. Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period 4. Patients requiring oxygen therapy for chronic hypoxemia (excluding acute COPD exacerbation). This is typically patients requiring oxygen therapy greater than15 h per day delivered by home oxygen cylinder or concentrator. 5. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1. Patients who develop a respiratory tract infection between Visit 1 and Visit 3 must discontinue from the trial, but may be permitted to re-enroll at a later date (at least 6 weeks after the start of the respiratory tract infection) 6. Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis 7. Patients with a history (up to and including Visit 1) of asthma indicated by (but not limited to). a) blood eosinophil count greater than 400 per mm3 b) onset of respiratory symptoms prior to age 40 years 8. 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 greater than 8.0 % of total Hb measured at Visit 1 9. 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 stable AF), uncontrolled hypertension, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state or any condition which in the investigator’s opinion might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study 10. Any patient with lung cancer or a history of lung cancer 11. Any patient with active cancer or a history of cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localized basal cell carcinoma (without metastases) of the skin is acceptable. Patients with a history of cancer (excluding lung cancer) and 5 years or more disease free survival time may only be included in the study by agreement with Novartis Headquarters personnel on a case-by-case basis 12. Patients with a history (or family history) of long QT syndrome or whose QTc interval (Bazett’s) measured at Visit 1 or Visit 3 is prolonged. greater than 450 ms (males) or greater than 470 ms (females) as assessed by the central ECG interpretation (Visit 1) or investigator’s interpretation of the pre-dose ECGs (Visit 3). Patients who fail the screening ECG (with the exception of machine failures) should not be re-screened. 13. Patients with a history of hypersensitivity to any of the study drugs or to drugs with similar chemical structures including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof 14. Patients who do not maintain regular dayornight, wakingorsleeping cycles (e.g., night shift workers) 15. Patients who have had treatment with investigational drugs at the time of enrollment, or within 30 days or 5 half-lives prior to Visit 1, whichever is longer. 16. Patients who have had live attenuated vaccinations within 30 days prior to Visit 1 or during the run-in period. Inactivated Influenza vaccination, pneumococcal vaccination or any other inactivated vaccine is acceptable provided it is not administered within 48 h prior to Visits 1, 2 or 3. 17. Treatments for COPD and allied conditions. the following medications must not be used prior to Visit 1 for at least the minimum washout period specified below or at any time during the study. a) The long acting anti-cholinergic agent tiotropium. 7 days b) Short acting anti-cholinergics. 8 h c) Fixed combinations of β2-agonists and inhaled corticosteroids. 48 h (Patients taking fixed dose combination therapy must be switched to an equivalent inhaled corticosteroid monotherapy plus salbutamol or albuterol as rescue therapy) d) Fixed combinations of short acting β2-agonists and short acting anticholinergics (e.g. Combivent). 8 h e) LABAs. 48 h f) SABAs (other than those prescribed in the study). 6 h g) Theophylline and other xanthines. 1 week h) Parenteral or oral corticosteroids. 1 month 18. Treatments for COPD and allied conditions. The following medications should not be used unless they have been stabilized. a) Cromoglycate, nedocromil, ketotifen, inhaled or nasal corticosteroids and leukotriene antagonists.
• at least one month prior to Visit 1 b) Antihistamines (excluding those in 20c below).
• at least 5 days prior to Visit 1 19. Other excluded medications. a) Non-potassium sparing diuretics (unless administered as a fixed dose combination with a potassium conserving drug) b) Beta-blocking agents c) Cardiac anti-arrhythmics Class Ia (e.g., disopyramide, procainamide, quinidine), Class III (e.g., amiodarone, dofetilide, ibutilide, sotalol), terfenadine, astemizole, mizolastin and any other drug with potential to significantly prolong the QT interval. d) Tricyclic antidepressants and monoamino-oxidase inhibitors. [Fluoxetine or any other selective serotonin uptake receptor inhibitor may only be permitted if the patient’s treatment regimen has been stable for at least 1 month prior to Visit 1, their Visit 1 ECG is normal and they have no clinical evidence of prior ECG abnormalities] 20. Patients unable to successfully use a dry powder inhaler device or perform spirometry measurements 21. Patients with a known history of non-compliance to medication or who are unable or unwilling to complete a Patient Diary.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Forced expiratory volume in 1 second (FEV₁) after 12 weeks of treatment measured 24 hours after having taken medication	After 12 weeks of treatment

Secondary Outcome Measures

Name	Time	Method
Total score of St.George's Respiratory Questionnaire	26 weeks
Health related quality of life assessments	26 weeks
Lung function tests (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC])	26 weeks
Trough FEV1	26 weeks
Effect of indacaterol on percentage of "days of poor control" of COPD over 26 weeks	26 weeks
Time to first COPD exacerbation and COPD exacerbation rate	26 weeks
Standardized area under the curve (AUC) for FEV1	26 weeks

Trial Locations

Locations (11)

Apollo Hospital; 🇮🇳 Hyderabad, ANDHRA PRADESH, India

Asthama Bhawan Sawai Maan Singh Medical College; 🇮🇳 Jaipur, RAJASTHAN, India

Asthma Allergy Centre; 🇮🇳 Mumbai, MAHARASHTRA, India

Chennai Thoracic Research Institute; 🇮🇳 Chennai, TAMIL NADU, India

Christian Medical College; 🇮🇳 Vellore, TAMIL NADU, India

Kerala Institute Of Medical Sciences; 🇮🇳 Anayara., P.O., India

KMC Hospital; 🇮🇳 Bangalore, KARNATAKA, India

Osmania Hospital; 🇮🇳 Hyderabad, ANDHRA PRADESH, India

PSG Hospital; 🇮🇳 Coimbatore, TAMIL NADU, India

Sri Ramkrishna Hospital; 🇮🇳 Coimbatore, TAMIL NADU, India

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Apollo Hospital

🇮🇳Hyderabad, ANDHRA PRADESH, India

Dr. Pradyut Waghray

Principal investigator

09246531036

pradyut_waghray@rediffmail.com