This study in healthy volunteers aimed to demonstrate similar PK and PD properties of the new short-acting human soluble insulin, Julphar Insulin R, and the already approved reference insulin, Huminsulin® Normal. The trial participants received both study treatments on two separate dosing days.
The daily injection of insulin is a necessity for many patients with diabetes mellitus in order to treat hyperglycemia. Julphar Insulin R and Huminsulin® Normal are both soluble insulins intended for subcutaneous administration and consist of a neutral solution containing recombinant human insulin as the active ingredient. The new insulin, Julphar Insulin R is biosimilar to Huminsulin® Normal. Demonstration of bioequivalence from a PK and PD perspective of the two insulins are necessary to achieve market approval for Julphar Insulin R.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
26
investigational insulin, Julphar Insulin R (soluble human insulin)
marketed product, Huminsulin® Normal (soluble human insulin
Profil Institut für Stoffwechselforschung GmbH
Neuss, Germany
PK: AUCins.0-12h, area under the serum insulin concentration time curve from 0 to 12 hours
primary endpoint according EMA guideline
Time frame: 12 hours
PK: Cins.max, maximum serum insulin concentration
primary endpoint according EMA guideline
Time frame: 12 hours
PD: AUCGIR.0-last, area under the glucose infusion rate curve from 0 hours until the end of the glucose clamp
primary endpoint according EMA guideline
Time frame: 12 hours
PD: GIRmax, maximum glucose infusion rate
primary endpoint according EMA guideline
Time frame: 12 hours
PK: AUCins.0-4h,area under the serum insulin concentration time curve from 0 to 4 hours
Time frame: 4 hours
PK: AUCins.0-6h,area under the serum insulin concentration time curve from 0 to 6 hours
Time frame: 6 hours
PK: AUCins.6-12h, area under the serum insulin concentration time curve from 6 to 12 hours
Time frame: 12 hours
PK: AUCins.0-infinity, area under the serum insulin concentration time curve from 0 (dosing) to infinity
Time frame: 12 hours
PK: tmax, time to maximum serum insulin concentration
Time frame: 12 hours
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PK: t50%-early, time to serum insulin increased to 50%, respectively of maximum serum insulin concentration
Time frame: 12 hours
PK: t50%-late, time to serum insulin decreased to 50%, respectively of maximum serum insulin concentration
Time frame: 12 hours
PK: t½, terminal serum elimination half-life calculated as t½=ln2/λz
Time frame: 12 hours
PK: λz, terminal elimination rate constant of insulin
Time frame: 12 hours
PK: MRT, mean residence time
Time frame: 12 hours
PK: CL/F, total body clearance
Time frame: 12 hours
PK: V/F, volume of distribution
Time frame: 12 hours
PD: AUCGIR0-4h, AUCGIR0-6h, AUCGIR6-last, areas under the glucose infusion rate curve in the indicated time-intervals
Time frame: 12 hours
PD: tGIRmax, time to maximum glucose infusion rate curve
Time frame: 12 hours
PD: tGIR50%-early, time to GIR increased to 50%, respectively of maximum GIR value
Time frame: 12 hours
PD: tGIR50%-late, time to GIR decreased to 50%, respectively of maximum GIR value
Time frame: 12 hours
PD: onset of action - time from trial product administration until blood glucose concentration has decreased at least 0.3 mmol/L (5 mg/dL) from baseline
baseline is defined as the mean of blood glucose levels measured with Super GL analyser at -6, -4,and -2 minutes before trial product administration
Time frame: 12 hours
Adverse events
Time frame: from first trial drug administration until final examination (up to 30 days for each patient)
Hypoglycaemic events
Time frame: from first trial drug administration until the final examination (up to 30 days for each patient)
Physical examination findings
Time frame: from screening until the final examination (up to 58 days for each patient)
Vital signs recordings
Time frame: from screening until the final examination (up to 58 days for each patient)
Electrocardiograms
Time frame: from screening until the final examination(up to 58 days for each patient)
Laboratory safety variables (haematology, biochemistry, and urinalysis)
Time frame: from screening until the final examination (up to 58 days for each patient)
Assessment of local tolerability at the injection site
The local tolerability at the injection site will be evaluated by means of the following assessments: * Spontaneous pain * Pain on palpation * Itching * Erythema * Oedema * Induration Each of these assessments will be reported on a scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe).
Time frame: from first trial drug administration until the final examination (up to 58 days for each patient)