AusPAR: Ivabradine - Therapeutic Goods Administration

AusPAR Coralan Ivabradine Servier Laboratories (Australia) Pty Ltd PM-2010-03269-3-3
Final 31 October 2012
Therapeutic Goods Administration
“during the study” and more detailed analysis was presented only on the TEAEs that
occurred “on treatment”.
Analysis of TEAEs that occurred “during the study” showed that in total 20142 TEAEs
were reported in 4862 patients (74.9%, 41.0%PY 32) with similar frequencies in each
treatment group (75.5% [2439/ 3232] and 74.3% [2423/ 3260], in the ivabradine and
placebo groups, respectively). The most frequently reported TEAEs by System Organ
Classification (SOC) in the ivabradine group were Cardiac disorders (43.0%, 23.4%PY
versus 43.0%, 23.7%PY, in the ivabradine and placebo groups, respectively), Infections
and infestations (22.1%, 12.0%PY versus 24.6%, 13.6%PY, respectively), Metabolism and
nutrition disorders (15.5%, 8.5%PY versus 16.2%, 9.0%PY, respectively), Investigations
(14.9%, 8.1%PY versus 10.9%, 6.0%PY, respectively) and Vascular disorders (14.8%,
8.0%PY versus 14.3%, 7.9%PY, respectively). The principal SOCs reported at higher
incidence rates in the ivabradine group than in the placebo group where the difference
was > 1% were Investigations (14.9%, 8.1%PY versus 10.9%, 6.0%PY, respectively) and
Eye disorders (6.3%, 3.4%PY versus 3.4%, 1.9%PY, respectively).
Analysis of TEAEs that occurred “on treatment” showed that in total, 17496 TEAEs were
reported in 4806 patients (74.0%, 44.1%PY) with similar frequencies in each treatment
group (74.7% [2414/ 3232] and 73.4% [2392/ 3260], in the ivabradine and placebo
groups, respectively). The most frequently reported TEAEs by SOC in the ivabradine group
were similar to those in the “during study” analysis and were Cardiac disorders (41.2%,
24.7%PY versus 41.6%, 24.7%PY, in the ivabradine and placebo groups, respectively),
Infections and infestations (19.6%, 11.7%PY versus 22.4%, 13.3%PY, respectively),
Investigations (14.0%, 8.4%PY versus 10.0%, 5.9%PY, respectively), Metabolism and
nutrition disorders (13.9%, 8.3%PY versus 14.7%, 8.7%PY, respectively) and Vascular
disorders (13.5%, 8.1%PY versus 13.0%, 7.7%PY, respectively). The principal SOCs
reported at higher incidence rates in the ivabradine group than in the placebo group
where the difference was > 1% were Investigations (14.0%, 8.4%PY versus 10.0%,
5.9%PY, respectively), Eye disorders (6.1%, 3.7%PY versus 3.2%, 1.9%PY, respectively)
and General disorders and administration site conditions (9.7%, 5.8%PY versus 8.8%,
5.2%PY, respectively).
Analysis of TEAEs that occurred “on treatment” showed that the most frequently reported
TEAEs in both groups by preferred term were cardiac failure (21.7%, 13.0%PY versus
26.0%, 15.4%PY, in the ivabradine and placebo groups, respectively), atrial fibrillation
(8.3%, 4.9%PY versus 6.7%, 4.0%PY, respectively) and blood pressure inadequately
controlled (7.1%, 4.2%PY versus 6.1%, 3.6%PY, respectively). A plot of the 20 most
frequent on-treatment TEAEs by preferred term in the ivabradine and placebo groups
showedg that the principal TEAEs occurring more frequently in the ivabradine group than
in the placebo group were atrial fibrillation (8.3%, 4.9%PY versus 6.7%, 4.0%PY,
respectively), blood pressure inadequately controlled (7.1%, 4.2%PY versus 6.1%,
3.6%PY, respectively), asymptomatic bradycardia 33 (HR decreased) (5.6%, 3.4%PY versus
1.4%, 0.8%PY, respectively), symptomatic bradycardia (4.6%, 2.7%PY versus 0.9%,
0.5%PY, respectively) and phosphenes (2.8%, 1.7%PY versus 0.5%, 0.3%PY, respectively).
Other studies
Not applicable.
32 In the study, annual incidence was calculated as % patient-years (%PY). This was calculated as the ratio
between the number of patients having experienced the events and the number of patient-years,
expressed for 100 patient-years.
33 HR < 50 bpm
Page 38 of 101