Pharmacokinetic (PK) Bioequivalence and Pharmacodynamics (PD) of Julphar Insulin N and Huminsulin® Basal

Phase 1

Completed

• Conditions: Diabetes Mellitus
• Interventions: Drug: Julphar Insulin N (human isophane insulin); Drug: Huminsulin® Basal (NPH, human isophane insulin)

• Registration Number: NCT02634528
• Lead Sponsor: Julphar Gulf Pharmaceutical Industries

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2015-12-11
• Study First Submitted QC: 2015-12-17
• Study First Posted: 2015-12-18
• Study Start: 2016-11-16
• Primary Completion: 2017-01-20
• Study Completion: 2017-01-20
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-01
• Last Update Posted: 2020-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 85

Inclusion Criteria

• Signed and dated informed consent obtained before any trial-related activities. (Trial-related activities are any procedures that would not have been performed during normal management of the subject).
• Healthy male subject.
• Age between 18 and 55 years, both inclusive.
• Body Mass Index (BMI) between 18.5 and 28.0 kg/m^2, both inclusive.
• Fasting plasma glucose concentration ≤100 mg/dL.

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Exclusion Criteria

• Known or suspected hypersensitivity to IMPs or related products.
• Previous participation in this trial. Participation is defined as randomised.
• Receipt of any medicinal product in clinical development within 3 months before screening.
• Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the Investigator.
• Any history or presence of clinically relevant cardiovascular, pulmonary, respiratory, gastrointestinal, hepatic, renal, metabolic, endocrinological haematological, dermatological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness as judged by the Investigator.
• Surgery within 12 weeks before the start of the study or blood donation of more than 500 mL (or considerable blood loss) or plasma donation within the last 3 months.
• Increased risk of thrombosis, e.g., subjects with a history of deep leg vein thrombosis or family history of deep leg vein thrombosis, as judged by the Investigator.
• Clinically significant abnormal values for haematology, biochemistry, coagulation, or urinalysis as judged by the Investigator.
• Supine blood pressure (BP) at screening (after resting for 5 minutes in a supine position) outside the range of 90 to 140 mmHg for systolic BP or 50 to 90 mmHg for diastolic BP (excluding white-coat hypertension; therefore, if a repeated measurement shows values within the range, the subject can be included in the trial) and/or resting supine pulse < 50 beats per minute.
• Clinically significant abnormal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position at screening, as judged by the Investigator.
• Any disease or condition that, in the opinion of the Investigator, would represent an unacceptable risk for the subject's safety.
• Positive to the screening test for Hepatitis Bs antigen or Hepatitis C antibodies and/or a positive result to the test for HIV-1/2 antibodies or HIV-1 antigen.
• History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
• Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol.
• Any medication (prescription and non-prescription drugs) within 14 days before first trial drug administration and/or anticoagulant therapy, with the exception of stable treatment with thyroid hormones, paracetamol and ibuprofen for occasional use to treat pain.
• Significant history of alcoholism or drug abuse as judged by the Investigator or consuming more than 21 units of alcohol per week (one unit of alcohol equals about 330 mL of beer, one glass of wine of 120 mL, or 40 mL spirits).
• A positive result in the alcohol and/or urine drug screen at the screening visit.
• Smoker (defined as a subject who is smoking more than 5 cigarettes or the equivalent per day) who is not able or willing to refrain from smoking and use of nicotine substitute products 1 day before and during the inpatient period.
• Subject with mental incapacity or language barriers precluding adequate understanding or cooperation or who, in the opinion of the Investigator, should not participate in the trial.
• Potentially noncompliant or uncooperative during the trial, as judged by the Investigator.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Julphar Insulin N	Julphar Insulin N (human isophane insulin)	Julphar Insulin N, human isophane insulin, 100 IU/mL, single subcutaneous injection of 0.6 IU/kg body weight
Huminsulin® Basal	Huminsulin® Basal (NPH, human isophane insulin)	Huminsulin® Basal, neutral protamine hagedorn (NPH), human isophane insulin, 100 IU/mL, single subcutaneous injection of 0.6 IU/kg body weight

Primary Outcome Measures

Name	Time	Method
PK: AUCins.0-24h, area under the serum insulin concentration curve from 0 to 24 hours	24 hours	Primary endpoints according EMA guidelines
PK: Cins.max, maximum observed insulin concentration	24 hours	Primary endpoints according EMA guidelines

Secondary Outcome Measures

Name	Time	Method
PK: t½, terminal serum elimination half-life calculated as t½=ln2/λz	24 hours
PD: AUCGIR.0-6h, AUCGIR.0-12h, areas under the glucose infusion rate curve in the indicated time-intervals	12 hours
Changes in Electrocardiogram recordings	from screening to final examination (up to 61 days for each patient)
PK: AUCins.0-∞, area under the serum insulin concentration-time curve from 0 hours to infinity	24 hours
PD: tGIR.max, time to maximum glucose infusion rate	24 hours
Physical examination findings	from screening to final examination (up to 61 days for each patient)
PK: λz, terminal elimination rate constant of insulin	24 hours
PD: AUCGIR.0h-last, area under the glucose infusion rate curve from 0 hours until the end of clamp	24 hours
PD: GIRmax, maximum observed glucose infusion rate	24 hours
Adverse events	from first dosing until final examination (up to 39 days for each patient)
PK: AUCins.0-6h, AUCins.0-12, areas under the serum insulin concentration curve in the indicated time intervals	12 hours
PK: tmax, time to maximum observed serum insulin concentration	24 hours
PD: Onset of action, time from trial product administration until blood glucose concentration has decreased at least 5 mg/dL from baseline	24 hours	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
Local tolerability findings	dosing period (up to 25 days for each patient)	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
Laboratory safety parameters	from screening to final examination (up to 61 days for each patient)
Changes in vital signs	from screening to final examination (up to 61 days for each patient)

Trial Locations

Locations (1)

Profil Neuss GmbH; 🇩🇪 Neuss, Germany