Long-Term Efficacy and Tolerability of an Emollient Containing Glycerol and Paraffin for Moderate-to-Severe Uremic Xerosis: A Randomized Phase 3 Study.

Abstract

Introduction: There is an unmet need for effective topical therapies for patients with uremic xerosis and chronic kidney disease-associated pruritus (CKD-aP). The long-term efficacy and tolerability of an emollient containing glycerol 15% and paraffin 10% (V0034CR) was evaluated in a phase 3 study.

Methods: In this randomized, double-blind, two-parallel group, vehicle-controlled study, patients with moderate-to-severe uremic xerosis were randomized to once-daily application of V0034CR or vehicle control for 28 days (period I). This was followed by a treatment-free period of ≤ 21 days (period II), then all patients received open-label treatment with V0034CR for ≥ 84 days (period III). Outcomes included treatment response at the end of period I (El Gammal's xerosis severity score), instrumental measures of scaling (D-Squame technique), time to relapse during period II, rate of recurrence during period III, pruritus severity over time, patient acceptability, and adverse events (AEs).

Results: The intent-to-treat population comprised 235 patients randomized to V0034CR (n = 118) or vehicle control (n = 117) during period I. Treatment response at the end of period I was achieved by 71 patients (60.2%) in the V0034CR group versus 48 (41.0%) with vehicle control (p = 0.0041). This coincided with greater reductions in the total surface area of squames (p = 0.001 vs vehicle control). Xerosis relapsed progressively without treatment in period II; however, remission was durable under maintenance therapy in period III. Improvements in pruritus severity were comparable between V0034CR and vehicle control, suggesting that the antipruritic effect of V0034CR was mainly exerted by its oil-in-water emulsion base. V0034CR had high patient acceptability and was well tolerated; the most common treatment-related AEs were irritation or erythema (2.1%), exacerbated pruritus (1.3%), and vesicles at the application site (0.9%).

Conclusion: These data support the use of V0034CR, with its hydrating and occlusive properties, for the long-term management of patients with moderate-to-severe uremic xerosis and CKD-aP.

Trial registration: ClinicalTrials.gov identifier NCT01084148; EudraCT number 2006-002201-31.