Neurotoxicity occurs in up to 50% of kidney transplant recipients (KTR). Tremor is the most common manifestation of neurotoxicity. It is believed that Tacrolimus (TAC) is most often associated with tremor in a 2-hour timeframe around peak serum concentrations (C_max). Reduction or cessation of TAC may possibly reduce tremor symptoms but may increase the risk for rejection. Once-daily TAC tablets (LCP-Tacro; Veloxis Pharmaceuticals) is a novel extended release MeltDose formulation of tacrolimus that has a reduced peak concentration with comparable AUC exposure, and administered at a reduced dose of ∼30% vs. standard TAC. We examined if converting stable TAC patients who have complaint of tremor with a standard TAC formulation to LCP-Tacro results in improvement in hand tremor. Tremor pre- and 7 days post-conversion was evaluated by independent, blinded neurologists using the Fahn-Tolosa-Marin (FTM) tremor rating scale and by the Tremorometer™, an accelerometry device that measures frequency and amplitude of tremor. Patients completed the PGI (Patient Global Impression of Change), a 7-point scale assessing tremor change. A preliminary analysis on the data currently available on the first 16 subjects was performed (mean age 47.2±14.08; 68.8% male; 87.5% white). Mean percent change from baseline in FTM Total Tremor Score (TRS) was -16.23% ± 23.34. TAC-induced tremor amplitude (milli-g) was reduced by 31 with movement (finger-to-nose) and 12 with posture-holding. Tremor frequency was in the typical drug-induced range of 8 Hz. Mean TAC trough levels (ng/mL) were: pre-conversion: 7.18±2.27 and post-conversion: 6.78±2.9. PGI ratings showed ‘much improvement’ in 19%; ‘a little better’ in 63%; and ‘no change’ in 19%. To our knowledge this is the first trial in KTR that utilizes a sophisticated and reproducible measurement of tremor. These preliminary results suggest LCP-Tacro may be associated with clinically meaningful improvement of hand tremor and may be an alternative for patients experiencing tremor due to immediate-release tacrolimus. Enrollment in this study is on-going; results on the planned full cohort are anticipated to be available for presentation.

Langone, A.: Grant/Research Support, Veloxis Pharmaceuticals. Gedaly, R.: Grant/Research Support, Veloxis Pharmaceuticals. Steinberg, S.: Grant/Research Support, Veloxis Pharmaceuticals. Shah, T.: Grant/Research Support, Veloxis Pharmaceuticals. Nigro, V.: Employee, Veloxis Pharmaceuticals.

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