The trial is a randomized, double-blind First in Human trial to evaluate the safety and tolerability of ZP4207 in healthy volunteers (HV) and in insulin-induced hypoglycemic T1D (type 1 diabetes) subjects as compared to native glucagon. The trial includes two parts. Part 1 includes dose escalation of ZP4207 in cohorts of 8 subjects. In each cohort, subjects will be randomized 3:1 to receive either a single ascending dose of ZP4207 (6 subjects) or a single fixed dose (SD) of native glucagon (2 subjects). The doses will be administered s.c. in 4-5 cohorts and i.m. in 3 cohorts. Part 2 includes two sequence groups of 10 hypoglycemic T1D subjects. The subjects will be treated with fixed single doses of ZP4207 and native glucagon s.c. in a sequential cross-over design in a randomized treatment order.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
111
Profil GmbH
Neuss, Germany
Safety and Tolerability: Number of participants with adverse events
Time frame: 28 days
Safety and Tolerability: Changes or findings from baseline in clinical safety laboratory assessments
Time frame: 28 days
Safety and Tolerability: Changes or findings from baseline in physical examination
Time frame: 28 days
Safety and Tolerability: Changes or findings from baseline in vital signs
Time frame: 28 days
Safety and Tolerability: Changes or findings from baseline in ECG
Time frame: 28 days
Safety and Tolerability: Findings in local tolerability
Time frame: 28 days
Pharmacokinetics (PK): Area under the curve (AUC) from time-point 0 until 300min
Time frame: 5 hours
Pharmacokinetics: maximum observed concentration of ZP4207 (Cmax)
Time frame: 5 hours
Pharmacokinetics: time to maximum observed concentration of ZP4207 (tmax)
Time frame: 5 hours
Pharmacokinetics: terminal elimination rate constant estimated during the terminal phase of ZP4207 (λz)
Time frame: 5 hours
Pharmacokinetics: the terminal plasma elimination half-life of ZP4207 (t½),
Time frame: 5 hours
Pharmacokinetics: apparent volume of distribution of ZP4207 based on plasma concentration values (Vz), estimated during the terminal Phase (f): (Vz/f)
Time frame: 5 hours
Pharmacokinetics: apparent plasma clearance rate of ZP4207(CL) estimated during the terminal Phase (f)
Time frame: 5 hours
Pharmacokinetics: mean residence time for plasma ZP4207 (MRT)
Time frame: 5 hours
Pharmacodynamics (PD): Area under the Plasma glucose curve from time-point 0 until 300 min (AUCgluc 0-300)
Time frame: 5 hours
Pharmacodynamics: maximum observed concentration (Cmax)
Time frame: 5 hours
Pharmacodynamics: time to maximum observed concentration (tmax)TPG≥70mg/dL
Time frame: 5 hours
Pharmacodynamics: Time to plasma glucose equal or above (70 mg/dL)
Time frame: 5 hours
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