October 2012 Australian Public Assessment Report for Ivabradine Proprietary Product Name: Coralan Sponsor: Servier Laboratories
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Table 15. Continued
Analysis of treatment-related SAEs that occurred “on treatment” showed that overall 108 patients experienced at least 1 treatment-related SAE and that the incidence was higher in the ivabradine group compared to the placebo group (2.0% [66/3232], 1.2%PY versus1.3% [42/3260], 0.8%PY in the ivabradine and placebo groups, respectively). The most frequently reported treatment-related SAEs by SOC in both groups were Cardiac disorders (1.7%, 1.0%PY versus 0.6%, 0.4%PY, in the ivabradine and placebo groups, respectively) and Nervous system disorders (0.1%, < 0.1%PY versus 0.2%, 0.1%PY, respectively). Treatment-related SAEs in the other SOCs occurred at an incidence rate of 0.1% in either treatment group. Treatment-related SAEs (preferred term) that were reported by 5 patients in the ivabradine group (that is, an incidence rate of >0.1%) were cardiac failure (0.4% [12/3232], 0.2%PY versus 0.3% [8/3260], 0.2%PY in the ivabradine and placebo groups, respectively), symptomatic bradycardia (0.4% [12/3232], 0.2%PY versus<0.1% [1/3260], <0.1%PY, respectively), atrial fibrillation (0.2% [7/3232], 0.1%PY versus<0.1% [1/3260], <0.1%PY, respectively) and atrioventricular block complete (0.2% [5/3232], 0.1%PY versus 0% [0/3260], 0%PY, respectively). DeathsA total of 1074 deaths (16.5%, 9.1%PY) from any cause were reported “during the study”; 510 deaths (15.8%, 8.6%PY) and 564 deaths (17.3%, 9.5%PY) in the ivabradine and placebo groups, respectively. The main causes of deaths in both treatment groups in the “during the study” analysis were sudden death (4.0% [128/3232] versus 4.5% [146/3260] in the ivabradine and placebo groups, respectively), cardiac failure (3.1% [100/3232] versus 3.8% [124/3260], respectively) and sudden cardiac death (2.7% [86/3232] versus 2.7% [88/3260], respectively). The sponsor has provided a tabulation of deaths to account for the difference between the numbers of deaths from any cause during the study (as described above) and results of all-cause mortality in the efficacy analyses (503 deaths in the ivabradine group versus 552 in the placebo group). Overall, 3 deaths (2 in the ivabradine group and 1 in the placebo group) were included in the efficacy analysis but not in safety analysis as they had not taken any study drugs. Twenty-two deaths were excluded from the efficacy analysis but included in safety analysis. This included 1 patient who was not randomised but were given placebo and 21 patients (9 in the ivabradine group and 12 in the placebo group) for whom the death dates were after the last visit date. A total of 828 “on-treatment” TEAEs with a fatal outcome were reported, 400 (12.4%, 7.4%PY) and 428 (13.1%, 7.8%PY) in the ivabradine and placebo groups, respectively. The main causes in both treatment groups were sudden death (3.4% [111/3232] versus 3.7% [119/3260] in the ivabradine and placebo groups, respectively), sudden cardiac death (2.3% [73/3232] versus 2.1% [68/3260], respectively) and cardiac failure (2.1% [69/3232] versus 2.8% [91/3260], respectively).
Discontinuation due to adverse eventsPivotal studyIn the analysis of TEAEs that led to study drug discontinuation, the sponsor considered two categories of events; TEAEs leading to permanent study drug discontinuation and TEAEs leading to a temporary interruption of the study drug without subsequent restart (due to reasons such as consent withdrawal, death, or temporal proximity to the last study visit). A total of 578 patients had TEAEs leading to permanent study drug discontinuation, 315 patients (9.8%, 5.8%PY) in the ivabradine group versus 263 (8.1%, 4.8%PY) in the placebo group. A total of 305 patients had TEAEs leading to temporary interruption of study drug without subsequent restart, 152 patients (4.7%, 2.8%PY) in the ivabradine group versus 153 (4.7%, 2.8%PY) in the placebo group. The sponsor had combined these two categories of treatment withdrawal (permanent, and temporary without restart) in the analysis of TEAEs that led to study drug discontinuation. Results showed that the incidence rate of study drug discontinuation was higher in the ivadrabine group compared to the placebo group (14.5% [467/3232] versus 12.8% [416/3260], respectively). The most frequently reported TEAEs leading to study drug discontinuation in the ivabradine group (by SOC) were Cardiac disorders (9.4%, 5.6%PY versus 8.3%, 4.9%PY in the ivabradine and placebo groups, respectively) and Investigations (1.1%, 0.6%PY versus 0.3%, 0.2%PY, respectively). Within the SOC of Cardiac disorders, the commonest TEAEs (by preferred term) leading to study drug discontinuation in the ivabradine group were atrial fibrillation (4.2%, 2.5%PY versus 3.5%, 2.1%PY, respectively), cardiac failures (2.0%, 1.2%PY versus 2.4%, 1.4%PY, respectively) and symptomatic bradycardia (0.6%, 0.4%PY versus 0.2%, 0.1%PY, respectively). Within the SOC of investigations, the commonest TEAE (by preferred term) leading to study drug discontinuation in the ivabradine group was asymptomatic bradycardia (HR decreased) (0.9%, 0.5%PY versus 0.2%, 0.1%PY, respectively). Other studiesNot applicable. Directory: sites -> default -> files files -> Answer True False 2 points Question 2 files -> Northern England’s set-jetting locations files -> Nstructions for Acquiring Excess Equipment online, through the 1033 Program files -> Occupational health and safety files -> The Black Panther Party’s Ten Point Program files -> International programs roel profile files -> Fermi Questions a guide for Teachers, Students, and Event Supervisors Lloyd Abrams, Ph. D. DuPont Company, cr&D/ccas experimental Station Wilmington, de 19880 files -> Personal Information Name: Maha Al-Ammari Nationality: Saudi Relationship Status Download 3.74 Mb. Share with your friends:
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