RESUMO
BACKGROUND: Tapencarium (RZL-012) (5-(3.6-dibromo-9H-carbazol-9-yl)-N, N, N-trimethylpentan-1-aminium chloride) is a novel injectable synthetic molecule with cytolytic properties, capable of reducing subcutaneous fat volume. OBJECTIVES: The goal of this 3-armed, randomized, double-blind, placebo-controlled phase 2b study was to determine the safety and efficacy of low- and high-dose RZL-012 vs placebo on submental fat (SMF) reduction. METHODS: Patients (n = 151, age 18-65 years) with excess SMF received a single treatment session of RZL-012 or placebo in the submental area, after which they were monitored for 84 days. SMF was assessed at baseline and after dosing with newly developed scales, namely the Clinician Chin Assessment Tool (C-CAT) and Subject Chin Assessment Tool (S-CAT). SMF was also assessed by magnetic resonance imaging (MRI) at screening and on Day 84 after treatment. RESULTS: The proportion of patients who had a 1-grade or 2-grade improvement in C-CAT and/or S-CAT on Day 84 vs baseline was significantly higher in the high-dose RZL-012 group vs the placebo group (P < .002). The relative percentage reduction in MRI-measured SMF volume (Day 84 vs screening) was significantly greater in the high-dose RZL-012 group vs the low-dose RZL-012 or the placebo group (P < .0001). Local injection site reactions were the most common adverse events (AEs). CONCLUSIONS: A single administration of RZL-012 into SMF resulted in significant improvement in submental appearance as assessed by clinicians, patients, and MRI. From a safety perspective, there were no serious AEs and no clinically significant changes in vital signs or laboratory tests over the course of the study.