Safety, Tolerability, and Clinical Effects of ZP8396, a Novel Long-Acting Amylin Analog-A Single Ascending Dose Trial

ZP8396 is an amylin analog designed for once weekly dosing that has demonstrated the potential to reduce body weight and improve glycemia in animal models of obesity and diabetes. We performed a randomized, double-blind, placebo-controlled trial to assess safety, pharmacokinetics, and pharmacodynamics of a single subcutaneous injection of ZP8396 in healthy lean and overweight male subjects. A total of 56 subjects (mean age was 38.1 years; mean BMI of 25.6 kg/m2) were randomized to ZP8396 or placebo (6:2) within seven dose cohorts ranging from 0.04 mg to 2.4 mg. The mean half-life of ZP8396 was approximately 10 days. After 1 week of observation, mean body weight decreased by -0.6%, 2.6%, 3.6%, and 4.2% from baseline following a single dose of placebo, 0.7 mg, 1.4 mg and 2.4 mg, respectively (Figure 1). ZP8396 was well tolerated, with no serious or severe adverse events (AEs) and no withdrawals. The most frequent related AEs were decreased appetite, nausea and vomiting, most events were mild and transient. No anti-drug antibodies were detected. In conclusion, administration of a single dose of ZP8396 resulted in dose-dependent and consistent reductions in body weight supporting the potential of ZP8396 as a treatment for obesity. Additional clinical studies of longer duration will be necessary to fully assess the clinical potential of ZP8396. Disclosure M. B. Olsen: Stock/Shareholder; Novo Nordisk A/S, Zealand Pharma A/S. U. Hövelmann: None. J. Griffin: Employee; Zealand Pharma A/S. K. M. Knudsen: Employee; Zealand Pharma A/S. T. Johansen: Employee; Zealand Pharma A/S. D. Kendall: Employee; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S, MannKind Corporation. T. Heise: Research Support; Adocia, AstraZeneca, Biocon, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Consultant; Gan & Lee Pharmaceuticals. Research Support; Genova. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Sanofi, Zealand Pharma A/S.