Cardiovascular and Renal Drugs Advisory
Committee Meeting
Safety:
1.
What is your level of concern (none, low, moderate, high) for the risk
of liver toxicity with use of ximelagatran:
a) For prevention of stroke and
systemic embolic events in patients with atrial fibrillation?
b) For secondary prevention of
venous thromboembolism (VTE) after 6 months standard treatment for an episode
of acute VTE?
c) For prevention of VTE in
patients undergoing elective total knee replacement surgery (TKR)?
For each response please explain.
2.
Based on currently available data, is it possible to identify patients
who are at risk for developing severe liver toxicity after exposure to ximelagatran?
3.
Did the sponsor’s study procedures for monitoring and managing patients
with regard to liver function adequately minimize the risk of severe liver
injury and liver failure in the clinical studies?
4.
Do you have other safety concerns regarding the long-term use of
ximelagatran (e.g. cardiac)? Regarding
the short-term use of ximelagatran?
5.
Do you recommend additional safety studies with
longer follow-up to address the possibility of delayed occurrence of liver
toxicity following short-term use?
6.
Regarding the potential risk of myocardial infarction/coronary artery
disease (MI/CAD) with short-term exposure to ximelagatran (mean 8 days) in
patients undergoing TKR, do you recommend further studies to assess the risk of
acute MI/CAD? If yes, what type of study(ies) do you recommend?
7.
Based on the currently available data, do you conclude that the
benefits of ximelagatran for short-term use for prevention of VTE in patients
undergoing elective total knee replacement surgery outweigh its risk?
Cardiovascular
and Renal Drugs Advisory Committee Meeting
Questions to the Committee
Cont.
Long-term Use: secondary prevention of VTE after 6 months standard treatment for an episode of
acute VTE
8. Based on the currently available data, do benefits of ximelagatran for secondary prevention of VTE (18 months) after 6 months standard treatment for an episode of acute VTE outweigh the risks for this indication?
9.
Is the non-inferiority margin of 2% compared to warfarin adequate to
ensure that ximelagatran is non-inferior to warfarin with respect to efficacy? If no, what should the non-inferiority margin be for the indication of prevention of stroke and
systemic embolic events in patients with atrial fibrillation?
10.
Based on the currently available data, do you conclude that the
benefits of ximelagatran for long-term use for prevention of stroke and
systemic embolic events in patients with atrial fibrillation outweigh its risk?