Switching STudy of Kidney TRansplant PAtients with Tremor to LCP-TacrO (STRATO): An open-label, multicenter, prospective phase 3b study

Abstract

Tremor is a common side effect of tacrolimus correlated with peak-dose drug concentration. LCPT, a novel, once-daily, extended-release formulation of tacrolimus, has a reduced Cmax with comparable AUC exposure, requiring a ~30% dose reduction vs. immediate-release tacrolimus. In this phase 3b study, kidney transplant recipients (KTR) on a stable dose of tacrolimus and with a reported clinically significant tremor were offered a switch to LCPT. Tremor pre- and seven d post-conversion was evaluated by independent, blinded movement disorder neurologists using the Fahn-Tolosa-Marin (FTM) scale and by an accelerometry device; patients completed the QUEST (quality of life in essential tremor) and the Patient Global Impression of Change. There were 38 patients in the mITT population. A statistically and clinically significant improvement in tremor (FTM score, amplitude as measured by the accelerometry device and QOL [p-values < 0.05]) resulted post-conversion. Change in QUEST was significantly (p = 0.006) correlated (R = 0.44) with change in FTM; 78.9% of patients reported an improvement after switching to LCPT (p < 0.0005). To our knowledge this is the first trial in KTR that utilizes a sophisticated and reproducible measurement of tremor. Results suggest LCPT is associated with clinically meaningful improvement of hand tremor and may be an alternative management approach in lieu of further dose reduction of immediate-release tacrolimus for patients experiencing tremor.