This study in healthy volunteers aims to demonstrate similar PK and PD properties of the new human isophane Insulin, Julphar Insulin N, and the already approved reference Insulin, Huminsulin® Basal. All participants will receive both study treatments on two separate dosing days.
Daily injections of insulin are a necessity for many patients with diabetes mellitus in order to treat hyperglycemia. Julphar Insulin N and Huminsulin® Basal are both intermediate-acting human isophane insulins, i.e. consist of a suspension containing a crystalline precipitate of isophane human insulin (NPH) complexed with protamine sulphate and zinc. The new insulin, Julphar Insulin N, is biosimilar to Huminsulin® Basal. Demonstration of similar absorption (PK) and effects (PD) are necessary to achieve market approval of Julphar Insulin N.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
85
investigational insulin: Julphar N (human isophane insulin), biosimilar
marketed reference product: Huminsulin® Basal (NPH, human isophane insulin)
Profil Neuss GmbH
Neuss, Germany
PK: AUCins.0-24h, area under the serum insulin concentration curve from 0 to 24 hours
Primary endpoints according EMA guidelines
Time frame: 24 hours
PK: Cins.max, maximum observed insulin concentration
Primary endpoints according EMA guidelines
Time frame: 24 hours
PK: AUCins.0-6h, AUCins.0-12, areas under the serum insulin concentration curve in the indicated time intervals
Time frame: 12 hours
PK: AUCins.0-∞, area under the serum insulin concentration-time curve from 0 hours to infinity
Time frame: 24 hours
PK: tmax, time to maximum observed serum insulin concentration
Time frame: 24 hours
PK: t½, terminal serum elimination half-life calculated as t½=ln2/λz
Time frame: 24 hours
PK: λz, terminal elimination rate constant of insulin
Time frame: 24 hours
PD: AUCGIR.0h-last, area under the glucose infusion rate curve from 0 hours until the end of clamp
Time frame: 24 hours
PD: GIRmax, maximum observed glucose infusion rate
Time frame: 24 hours
PD: AUCGIR.0-6h, AUCGIR.0-12h, areas under the glucose infusion rate curve in the indicated time-intervals
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Time frame: 12 hours
PD: tGIR.max, time to maximum glucose infusion rate
Time frame: 24 hours
PD: Onset of action, time from trial product administration until blood glucose concentration has decreased at least 5 mg/dL from baseline
baseline is defined as the mean of blood glucose levels from -6, -4, and -2 minutes before trial product administration as measured by the glucose clamp device
Time frame: 24 hours
Adverse events
Time frame: from first dosing until final examination (up to 39 days for each patient)
Local tolerability findings
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/infiltration * other Each of these assessments will be reported on a scale of 0 (none), 1 (mild), 2 (moderate) and 3 (severe). The evaluation and the actual time of the assessment will be recorded
Time frame: dosing period (up to 25 days for each patient)
Laboratory safety parameters
Time frame: from screening to final examination (up to 61 days for each patient)
Physical examination findings
Time frame: from screening to final examination (up to 61 days for each patient)
Changes in vital signs
Time frame: from screening to final examination (up to 61 days for each patient)
Changes in Electrocardiogram recordings
Time frame: from screening to final examination (up to 61 days for each patient)