Dasiglucagon is a stable glucagon analog being developed in the HypoPal® auto-injector to address the need for easy-to-use, fast and effective treatment of severe hypoglycemia in individuals with diabetes. In this pediatric Phase 3 trial, ZP4207-17086, the clinical efficacy and safety of 0.6 mg dasiglucagon administered subcutaneously (SC) (same dose as adults) was compared to placebo and with reference to GlucaGen®. In total, 42 eligible children with T1D between 6 and 17 years (6-11 years: 16 children and 12-17 years: 25 children) were randomized (2:1:1) to dasiglucagon, placebo or GlucaGen® and dosed following induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery, defined as first PG increase ≥20 mg/dL after treatment initiation without rescue glucose. The results showed that dasiglucagon 0.6 mg SC induced a fast and effective PG increase. The median time (95% CI) to recovery based on sampling time was 10 (8, 12) min for dasiglucagon vs. 30 (20, -) min for placebo (p<0.001); and 10 (8, 12) min for GlucaGen®. The estimated true time to recovery (interpolated between sampling times) showed that the median (95% CI) time was 8.7 (6.9, 10.6) min for dasiglucagon, 29.3 (18.5, -) min for placebo and 9.8 (7.4, 10.6) min for GlucaGen®. Nausea and vomiting are known side effects following administration of glucagon products and were reported for active treatments only: with dasiglucagon (6-11 years; nausea: 25% and vomiting: 25%; 12-17 years; nausea: 92% and vomiting: 67%) and with GlucaGen® (6-11 years; nausea: 50% and vomiting: 25%; 12-17 years; nausea: 17% and vomiting: 0%). No relationship between exposure (AUC0-5 hr or Cmax) to dasiglucagon and nausea and vomiting was found. No safety concerns were raised for dasiglucagon within the trial. In conclusion, consistent with adult phase 3 trials this study demonstrated a fast, effective treatment response with a median time to recovery of 10 min in children ≥ 6 years, and an overall safety profile similar to glucagon.
T. Battelino: Advisory Panel; Self; Medtronic, Sanofi. Consultant; Self; Indigo Diabetes. Research Support; Self; Medtronic, Novo Nordisk A/S, Zealand Pharma A/S. Speaker’s Bureau; Self; Abbott, AstraZeneca, Dexcom, Inc., Lilly Diabetes, Medtronic. Stock/Shareholder; Self; DreaMed Diabetes. R. Tehranchi: Employee; Self; Zealand Pharma A/S. A.E. Melgaard: Employee; Self; Zealand Pharma A/S. D. Skydsgaard: Employee; Self; Zealand Pharma A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S, Roche Diabetes Care. T.S. Bailey: Consultant; Self; Abbott, LifeScan, Inc., Novo Nordisk A/S, Sanofi US. Research Support; Self; Abbott, Ascensia Diabetes Care, Capillary Biomedical, Inc., Dance Biopharm Holdings, Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Kowa Pharmaceuticals America, Inc., Lexicon Pharmaceuticals, Inc., Medtronic, Medtrum, Novo Nordisk A/S, REMD Biotherapeutics, Sanofi-Aventis, Senseonics, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S. Speaker’s Bureau; Self; Medtronic, Sanofi US. L. DiMeglio: None. T. Danne: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Sanofi.