Patricia Walker1, Daniel Lee. 1. Private Practice, Carpinteria, CA, USA; Chief Medical Officer, Kythera Biopharmaceuticals, Inc., Calabasas, CA, USA.
Abstract
BACKGROUND: ATX-101 (deoxycholic acid injection, Kythera Biopharmaceuticals, Inc.) is a proprietary formulation of pure synthetic deoxycholic acid (DCA). It is undergoing clinical investigation as an injectable drug for contouring the submental area by reducing submental fat (SMF). When injected into subcutaneous fat, ATX-101 causes focal adipocytolysis, the targeted destruction of fat cells. OBJECTIVES: This phase 1 study evaluated the safety, pharmacokinetics (PK), and pharmacodynamic effects of ATX-101 (100-mg total dose). METHODS: Following PK evaluation of baseline endogenous DCA, lipids, and adipokines in the initial stage of the study (samples collected at hours 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, 15.5, and 24.5), 10 subjects received subcutaneous injections of ATX-101 into abdominal fat. PK evaluation of DCA, lipids, and adipokines was repeated in the second phase of the study. RESULTS: After ATX-101 injections, plasma concentration of DCA increased transiently, reached a maximum plasma concentration rapidly, and returned to endogenous concentrations within 12 h postdose. ATX-101 injection was not associated with any clinically meaningful changes in systemic concentrations of total cholesterol, total triglycerides, free fatty acids, C-reactive protein, or interleukin-6. Adverse events were mild in severity, transient, and showed a temporal relationship to dosing. CONCLUSIONS: This study demonstrated favorable safety and PK profiles, and no clinically meaningful changes in DCA, lipids, and proinflammatory cytokines following subcutaneous injection of ATX-101. Our results support continued clinical investigation of ATX-101 as an injectable drug to reduce SMF.
BACKGROUND:ATX-101 (deoxycholic acid injection, Kythera Biopharmaceuticals, Inc.) is a proprietary formulation of pure synthetic deoxycholic acid (DCA). It is undergoing clinical investigation as an injectable drug for contouring the submental area by reducing submental fat (SMF). When injected into subcutaneous fat, ATX-101 causes focal adipocytolysis, the targeted destruction of fat cells. OBJECTIVES: This phase 1 study evaluated the safety, pharmacokinetics (PK), and pharmacodynamic effects of ATX-101 (100-mg total dose). METHODS: Following PK evaluation of baseline endogenous DCA, lipids, and adipokines in the initial stage of the study (samples collected at hours 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, 15.5, and 24.5), 10 subjects received subcutaneous injections of ATX-101 into abdominal fat. PK evaluation of DCA, lipids, and adipokines was repeated in the second phase of the study. RESULTS: After ATX-101 injections, plasma concentration of DCA increased transiently, reached a maximum plasma concentration rapidly, and returned to endogenous concentrations within 12 h postdose. ATX-101 injection was not associated with any clinically meaningful changes in systemic concentrations of total cholesterol, total triglycerides, free fatty acids, C-reactive protein, or interleukin-6. Adverse events were mild in severity, transient, and showed a temporal relationship to dosing. CONCLUSIONS: This study demonstrated favorable safety and PK profiles, and no clinically meaningful changes in DCA, lipids, and proinflammatory cytokines following subcutaneous injection of ATX-101. Our results support continued clinical investigation of ATX-101 as an injectable drug to reduce SMF.