Saol International Development Limited: sodium dichloroacetate

The data presented in NDA 218679 failed to demonstrate substantial evidence of effectiveness for sodium dichloroacetate (DCA) for the treatment of pyruvate dehydrogenase complex deficiency (PDCD).

You proposed to establish substantial evidence of effectiveness using two adequate and well-controlled trials: SL1009-01 and SL1009-02.

The proposed post hoc analyses for the subgroup of subjects with Period 1 baseline ObsRO motor score = 8 were deemed inappropriate to determine the presence of a DCA treatment effect.

DCA with a nominal two-sided p-value < 0.05. However, the changes in the baseline plasma lactate were minimal and additional clinical and nonclinical data provided did not support the observed reduction in plasma lactate as a surrogate endpoint that predicts clinical benefit in PDCD.

To address this deficiency, submit the results of at least one new adequate and wellcontrolled trial demonstrating the effect of DCA on clinically meaningful endpoint(s) in the intended population.

If you intend to demonstrate substantial evidence of effectiveness based on a single adequate and well controlled trial, you will also need to provide adequate confirmatory evidence substantiating the results of your adequate and well controlled trial.

As substantial evidence of effectiveness of DCA for the treatment of PDCD was not established in this application, we cannot conclude that the known and potential risks with DCA in your application are outweighed by its benefit(s).

Therefore, for the potential benefits and risks to be adequately evaluated, the following issues, including those for premarketing risk assessment, and our recommendations for resolving those issues, must be addressed, in some manner, in the resubmission of your application.

2. You have not conducted a thorough QT/QTc study to evaluate the effect of DCA on QT interval prolongation and the currently available clinical safety database in the NDA is insufficient to assess the potential effect of DCA on the QT interval.

If you do not have a conditionally acceptable proprietary name, you may submit a Request for Proprietary Name Review to your IND.