Tremor is a common side effect of tacrolimus (tac) correlated with peak-dose drug concentration. Envarsus XR®, a novel, once-daily, extended-release formulation of tac, has a reduced C_max with comparable AUC exposure, requiring a ~30% dose reduction vs. immediate-release tac. In this Phase 3b study, kidney transplant recipients (KTR) on a stable dose of tac, at targeted exposure levels and with a reported clinically significant tremor were offered a switch to Envarsus XR as an alternative management approach in lieu of further dose reduction with immediate-release tac. Tremor pre- and 7 days 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 [QoL] in essential tremor) and the Patient Global Impression of Change. Previously reported results showed a statistically and clinically significant improvement in tremor, and improvement in QoL for 80% of patients switched from traditional twice-daily tac capsule to Envarsus XR. Here we report safety, trough levels, and dose adjustments from the two years' follow-up of the study among the 40 Envarsus XR-treated patients who entered the extended-use phase. Mean duration of treatment was 21.3±6.7 months; at least one dose adjustment (DA) was made in n=35 (87.5%) patients, mainly based on trough results; 32.5% had 1-2 DA, and 55% had ≥3 DAs. Mean trough levels were similar across the two years (range: 5.5-6.6 ng/mL at months 3, 6, 9, 12, 15, 18, 24). Most patients (95%) experienced ≥1 adverse event (AE); 83% were mild or moderate and only 2 patients discontinued Envarsus XR due to an AE; of the 13 serious AEs, none were considered study drug-related. These results show that Envarsus XR is not associated with any unexpected safety concerns. Once-daily Envarsus XR showed consistent trough levels across the extended follow-up.

CITATION INFORMATION: Steinberg S, Gedaly R, Chan L, Langone A. Two-Year Safety Results from the Phase 3b Switching Study of Kidney Transplant Patients with Tremor to LCP-Tacro (STRATO) Study. Am J Transplant. 2016;16 (suppl 3).

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