AusPAR: Ivabradine - Therapeutic Goods Administration

More documents

Recommendations

Info

AusPAR Coralan Ivabradine Servier Laboratories (Australia) Pty Ltd PM-2010-03269-3-3 Final 31 October 2012 Therapeutic Goods Administration Table 18. TEAEs in the subgroup of patients aged ≥ 75 years, compared to the overall study safety dataset. Safety dataset Subgroup “age ≥ 75 years” IVB PLB IVB PLB Any TEAEs 74.7% 73.4% 78.8% 77.6% Commonest TEAEs by SOC, in ivabradine group Commonest TEAEs by preferred term, in ivabradine group Main TEAEs (by preferred term) that were more frequent in the ivabradine group than in the placebo group cardiac disorders infections and infestations investigations cardiac failure atrial fibrillation blood pressure inadequately controlled atrial fibrillation blood pressure inadequately controlled asymptomatic bradycardia (HR decreased) symptomatic bradycardia phosphenes IVB= ivabradine; PLB= placebo 41.2% 19.6% 14.0% 21.7% 8.3% 7.1% 8.3% 7.1% 5.6% 4.6% 2.8% 41.6% 22.4% 10.0% 26.0% 6.7% 6.1% 6.7% 6.1% 1.4% 0.9% 0.5% cardiac disorders infections and infestations vascular disorders cardiac failure atrial fibrillation symptomatic bradycardia blood pressure inadequately controlled symptomatic bradycardia blood pressure inadequately controlled asymptomatic bradycardia (HR decreased) respiratory tract infection dizziness arthralgia 50.1% 26.2% 13.9% 28.6% 11.7% 7.4% 7.4% 7.4% 7.4% 5.7% 3.5% 2.7% 1.6% 47.3% 26.1% 14.2% 32.3% 11.6% 1.1% 6.0% 1.1% 6.0% 2.3% 1.4% 1.7% 0% Page 48 of 101
Clinical summary and conclusions First round benefit-risk assessment Benefits AusPAR Coralan Ivabradine Servier Laboratories (Australia) Pty Ltd PM-2010-03269-3-3 Final 31 October 2012 Therapeutic Goods Administration The potential benefits of ivabradine in the proposed additional indication are a reduction in morbidity and/or mortality of CHF patients. Overall, the study results showed statistically significant relative risk reductions in cardiovascular morbidity (as measured by cardiovascular hospitalisations and hospitalisations for worsening heart failure) but failed to demonstrate efficacy for improving the outcome of cardiovascular mortality. While the results showed that there was no increased risk of the mortality endpoints with ivabradine compared to placebo, there was no statistically significant difference in favour of ivabradine over placebo in most of the mortality endpoints analysed in the study in the general study population (RS dataset), where only the endpoint of death from heart failure was statistically significant (RRR 26%; p=0.014). There was no statistically significant difference in favour of ivabradine over placebo in all the mortality endpoints analysed in the study in the sub-population of patients who were on at least 50% of the optimal beta blocker dose (RSBBdose dataset). In fact, in the RSBBdose dataset, there was no discernible difference between treatment groups in the endpoints of all-cause mortality and of cardiovascular death (relative risk reduction of 1% and 0%, respectively). 34 Although subgroup analysis in RS population of the mortality endpoints showed an effect in favour of ivabradine in the subgroup of patients with baseline HR ≥77 bpm and this effect was statistically significantly more than in the subgroup of patients with baseline HR 70 years) is unclear” was noted by the clinical evaluator. The sponsor did an analysis of the primary composite endpoint and the secondary endpoints in the subgroups of patients “aged ≥ 70 years” (N=1500 [n=776 ivabradine, n=724 placebo]), “aged ≥ 70 34 Paragraph corrected (underlined text added) as per typographical error noted in Second Round Benefit- Risk Assessment; Benefits: “While the results showed that there was no increased risk of the mortality endpoints with ivabradine compared to placebo, there was no statistically significant difference in favour of ivabradine over placebo in most of the mortality endpoints analysed in the study in the general study population (RS dataset), where only the endpoint of death from heart failure was statistically significant (RRR 26%; p=0.014). There was no statistically significant difference in favour of ivabradine over placebo in all the mortality endpoints analysed in the study in the sub-population of patients who were on at least 50% of the optimal beta blocker dose (RSBBdose dataset). In fact, in the RSBBdose dataset, there was no discernible difference between treatment groups in the endpoints of all-cause mortality and of cardiovascular death (relative risk reduction of 1% and 0%, respectively).” 35 Sponsor comment: The analysis for statistical significance in the subgroups of patients with baseline HR≥ 77BPM and
Page 1 and 2: Australian Public Assessment Report
Page 3 and 4: Contents AusPAR Coralan Ivabradine
Page 5 and 6: Product background AusPAR Coralan I
Page 7 and 8: AusPAR Coralan Ivabradine Servier L
Page 17 and 18: Table 1. Analysis Sets and Subsets
Page 25 and 26: Table 6. Causes of deaths by treatm
Page 27 and 28: Analyses performed across trials (p
Page 31 and 32: Table 10. (ii) Pre-specified subgro
Page 37 and 38: Patient exposure AusPAR Coralan Iva
Page 39 and 40: Treatment-related adverse events (a
Page 41 and 42: Table 15. Continued AusPAR Coralan
Page 47: AusPAR Coralan Ivabradine Servier L
Page 63 and 64: Table 25. Incidence of TEAEs by age
Page 65 and 66: Second round benefit-risk assessmen
Page 67 and 68: Safety specification AusPAR Coralan
Page 69 and 70: CL3-067 (Follow up Measure; Ophthal
Page 85 and 86: Risk management plan AusPAR Coralan
Page 95 and 96: Table 35 AusPAR Coralan Ivabradine
Page 99 and 100:
AusPAR Coralan Ivabradine Servier L
Page 101:
Therapeutic Goods Administration PO
show all

AusPAR: Ivabradine - Therapeutic Goods Administration

Create successful ePaper yourself

Delete template?

Save as template?