Sponsor Novartis Pharmaceuticals

Transcription

1 Clinical Trial Results Database Page 1 Sponsor Novartis Pharmaceuticals Generic Drug Name Indacaterol Therapeutic Area of Trial Chronic Obstructive Pulmonary Disease (COPD) Indication studied: COPD Study Number CQAB149B2335S Title A 26-week treatment, multicenter, randomized, double blind, double dummy, placebo-controlled, adaptive, seamless, parallel-group study to assess the efficacy, safety and tolerability of two doses of indacaterol (selected from 75, 150, 300 & 600 μg o.d.) in patients with chronic obstructive pulmonary disease using blinded formoterol (12 μg b.i.d) and open label tiotropium (18 μg o.d.) as active controls Phase of Development Phase II/III Study Start/End Dates 23 Apr 2007 to 23 Aug 2008 Study Design/Methodology This study was a multicenter, double-blind, randomized, placebo and active controlled, adaptive and seamless, parallel-group study design consisting of 2 stages: a dose selection stage from which 2 out of 4 indacaterol doses were selected (150 and 300 µg once daily [o.d.] were selected) following interim analysis to continue into a second stage for comparisons of efficacy, safety and tolerability for up to 26 weeks total treatment. Centres 334 centers in 11 countries: Argentina (6), Canada (24), Germany (35), India (13), Italy (16), Korea (13), Spain (21), Sweden (6), Turkey (8), Taiwan (7), United States (185) Publication Ongoing

2 Clinical Trial Results Database Page 2 Objectives Primary objective(s) To demonstrate superiority of at least one of the selected doses of indacaterol (150 and 300 μg o.d.) to placebo with respect to 24 h post dose (trough) forced expiratory volume in 1 second (FEV 1 ) after 12 weeks of treatment in patients with COPD. Secondary objective(s) To demonstrate non-inferiority of at least one of the selected doses of indacaterol (150 and 300 μg o.d.) to open label tiotropium (18 μg o.d.) with respect to 24 h post dose (trough) FEV 1 following 12 weeks of treatment. To evaluate the effect of indacaterol (150 or 300 μg o.d.) to placebo on percentage of days of poor control reported over the 26 week randomized treatment period Safety objective(s): Included: To assess the safety and tolerability of indacaterol (150 or 300 μg o.d.) in terms of adverse events Test Product (s), Dose(s), and Mode(s) of Administration Indacaterol 75, 150, 300 and 600 μg o.d., administered once daily by the orally inhaled route via single dose dry powder inhaler (SDDPI) Reference Product(s), Dose(s), and Mode(s) of Administration Formoterol delivered via Aerolizer (Stage 1 only) Tiotropium (18 μg) dry powder capsules delivered via manufacturer s proprietary inhalation device (Handihaler ) Placebo to indacaterol delivered via SDDPI Placebo to formoterol delivered via Aerolizer Criteria for Evaluation Primary variables Trough FEV1 after 12 weeks of treatment Secondary variables Percentage of COPD 'days of poor control' over 26 weeks Safety and tolerability Included monitoring and recording all adverse events (AEs) and serious adverse events (SAEs) Statistical Methods Trough FEV 1 was analyzed using a mixed model containing treatment as a fixed effect with the baseline FEV 1 measurement, FEV 1 prior to inhalation and FEV 1 30 min post inhalation of salbutamol/albuterol (components of SABA reversibility at Day -14), FEV 1 prior to inhalation and

3 Clinical Trial Results Database Page 3 FEV 1 one hour post inhalation of ipratropium (components of anti-cholinergic reversibility at Day -13) as covariates. To reflect the randomization scheme the model included also the smoking status (current/ex-smoker) and country as fixed effects with center nested within country as a random effect. Estimates of adjusted treatment effects and of treatment contrasts were displayed along with the associated confidence intervals. The percentage of days of poor control was summarized by treatment and analyzed using the same mixed model as specified for the primary analysis, with baseline percentage of days of poor control used instead of baseline FEV 1. Study Population: Inclusion/Exclusion Criteria and Demographics Inclusion criteria: Male and female adults aged 40 years, with a diagnosis of COPD according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2005 and: Smoking history of at least 20 pack-years Post-bronchodilator FEV 1 <80% and 30% of the predicted normal value Post-bronchodilator FEV 1 /FVC (forced vital capacity) <70% (Post refers to within 30 min after inhalation of 400 μg of salbutamol) Key exclusion criteria: Patients who were hospitalized for a COPD exacerbation in the 6 weeks prior to screening Patients who had a respiratory tract infection within 6 weeks prior to screening Patients with concomitant pulmonary disease Patients with a history of asthma Patients with diabetes Type I or uncontrolled diabetes Type II Any patient with lung cancer or a history of lung cancer Patients with a history of certain cardiovascular co-morbid conditions

4 Clinical Trial Results Database Page 4 Number of Subjects Patient disposition

5 Clinical Trial Results Database Page 5 Demographic and Background Characteristics (treatments continued into Stage 2)

6 Clinical Trial Results Database Page 6 Primary Objective Results Trough FEV 1 (L) at Week 12 (imputed with LOCF): treatment comparisons (ITT population)

7 Clinical Trial Results Database Page 7 Secondary Objective Results Trough FEV 1 (L) at Week 12 (imputed with LOCF): treatment comparisons (ITT population) See the primary objective results table for indacaterol tiotropium comparisons Percentage of COPD days of poor control over 26 weeks: treatment comparisons (ITT population)

8 Clinical Trial Results Database Page 8 Safety Results Adverse events (including COPD exacerbations) overall and by primary system organ class - n (%) of patients (Safety population, treatments continued into Stage 2)

9 Clinical Trial Results Database Page 9 Serious Adverse Events and Deaths Deaths, other serious adverse events (including COPD exacerbations) and adverse events leading to permanent discontinuation of study drug n (%) of patients (Safety population, treatments continued into Stage 2) Date of Clinical Trial Report 03 Nov 2008 Date Inclusion on Novartis Clinical Trial Results Database 14 Aug 2009 Date of Latest Update 16 Dec 2009