Safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long‐acting glucagon analogue HM15136 in overweight and obese patients with co‐morbidities

Abstract

AbstractAimTo evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long‐acting glucagon analogue HM15136 in overweight/obese patients with co‐morbidities, with and without type 2 diabetes (T2D).Materials and MethodsThis was a phase 1, double‐blind, randomized, placebo‐controlled, two‐part trial with a 12‐week treatment period of once‐weekly subcutaneous HM15136 (0.02/0.04/0.06 mg/kg). Part 1 included patients with dyslipidaemia and/or hypertension and no T2D. Part 2 included patients with dyslipidaemia and/or hypertension plus T2D.ResultsIn part 1, 23/27 (85.2%) patients receiving HM15136 and all patients receiving placebo (9/9 [100%]) experienced a treatment‐emergent adverse event (TEAE). Five of 27 (18.5%) patients receiving HM15136 developed anti‐HM15136 antibodies. Dose‐dependent increases in mean HM15136 serum concentration and fasting plasma glucose (FPG) were observed, as were dose‐dependent weight reductions of 0.5%/2.3%/2.6% at doses of 0.02/0.04/0.06 mg/kg, respectively. In part 2, 8/12 (66.7%) patients receiving HM15136 and all patients receiving placebo (4/4 [100.0%]) reported a TEAE. Two (16.7%) patients developed anti‐HM15136 antibodies. Dose‐dependent increases in mean HM15136 serum concentration were observed. FPG of more than 200 mg/dL was reported in 4/9 (44.4%) and 2/3 (66.7%) patients receiving 0.02 and 0.06 mg/kg, respectively. The 0.06 mg/kg dose was not tolerated in part 2 because of hyperglycaemia. Patients receiving 0.02 mg/kg showed a 0.9% weight reduction. No serious TEAEs leading to discontinuation were reported in either study part.ConclusionsThis study of HM15136 provides a preliminary safety and tolerability profile with initial insights into its efficacy profile.