The purpose of the trial is to characterize the safety and tolerability of dasiglucagon 4 mg/mL following IV administration at increasing doses in healthy volunteers. One cohort of subjects will receive a SC dose of dasiglucagon to characterize the bioavailability of dasiglucagon following SC administration compared to IV administration. Furthermore, the trial aims to assess the potential effect of dasiglucagon on corrected QT interval (QTc) prolongation via a concentrationresponse analysis.
Hypoglycemia in patients with diabetes is defined as episodes of an abnormally low plasma glucose concentration. Hypoglycemia is a common, unpredictable, and potentially dangerous side effect of treatment of diabetes mellitus, especially with insulin or sulfonylureas. Dasiglucagon (ZP4207) is a stable peptide analog of human glucagon, available in a ready-to-use liquid formulation. Dasiglucagon is in development for the treatment of severe hypoglycemia in patients with diabetes mellitus. Dasiglucagon is a specific and full glucagon receptor agonist designed to mimic the effects of glucagon, having a fast absorption and elimination (minutes).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
60
Dasiglucagon injection
Placebo for Dasiglucagon injection
CRS Clinical Research Services Mannheim GmbH
Mannheim, Germany
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Change measures from baseline considering nausea, vomiting and diarrhea
Time frame: day 1, day 2, day 28
Clinical assessment of local tolerability at injection site by physical examination
Change measures from baseline in pain, redness, itching, edema, induration/infiltration of skin
Time frame: day-1, day 1, day 2, day 28
Occurrence of anti-drug antibodies (ADA)
Change measures from baseline
Time frame: day 1 and day 28
Plasma dasiglucagon profiles following IV administration, Area Under the Curve (AUC)
Change measures from baseline
Time frame: Pre-dose, 5, 15, 25, 40, 60, 80, 100, 120, 140, 180 and 240 min.
Plasma dasiglucagon profiles following SC administration, Area Under the Curve (AUC)
Change measures from baseline
Time frame: Pre-dose, 5, 15, 25, 35, 45, 60, 90, 130, 210 and 300 min.
Change-from-baseline in ECG for QTcF
Change measures from baseline
Time frame: From day -1 to day 2 and day 28
Change-from-baseline in ECG for heart rate (HR)
Change measures from baseline
Time frame: From day -1 to day 2 and day 28
Change-from-baseline in ECG for pulse rate (PR)
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Change measures from baseline
Time frame: From day -1 to day 2 and day 28
Change-from-baseline in ECG for QRS
Change measures from baseline
Time frame: From day -1 to day 2 and day 28
Frequency of treatment-emergent T-wave morphology changes and U-waves by Holter monitoring
Change measures from baseline
Time frame: From day -1 to day 2