Mallinckrodt Hospital Products IP Limited: Terlivaz

Federal Food, Drug, and Cosmetic Act for Terlivaz (terlipressin) 1 mg injection.

We acknowledge receipt of your resubmission dated March 12, 2020, which constituted a complete response to our November 4, 2009, action letter.

To address this requirement and support a claim for the treatment of adults with hepatorenal syndrome (HRS) type 1, you submitted the results of a randomized, double-blind, placebo-controlled trial comparing intravenous (IV) terlipressin to placebo in adult patients with HRS type | (CONFIRM).

In order to be counted in the primary endpoint, patients also needed to be alive without renal replacement therapy for at least 10 days after achieving verified HRS reversal.

We acknowledge your proposed risk mitigation strategy; however, the strategy has not been prospectively tested, and it is unclear whether its implementation would adversely impact terlipressin's efficacy for its proposed use.

To address this issue, you will need to conduct an adequate and well-controlled study that demonstrates an acceptable risk-benefit profile, perhaps utilizing the proposed risk mitigation strategy.

The primary endpoint and analytic plan should be discussed with and agreed upon by the FDA prior to initiation.

(8) Provide English translations of current approved foreign labeling not previously submitted.