Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes, Diabetes Type 1, Type 1, Basal, Insulin, Glargine, T1DM, Diabetes Mellitus, Insulin Dependent Diabetes
Brief summary
Primary objectives: To demonstrate biosimilarity with regard to the total and maximum pharmacokinetic exposure during one dosing interval (AUC ins. 0-24h, Cins. max) of Gan & Lee Insulin Glargine with Lantus® (US RLD / EU RP) in subjects with type 1 diabetes To demonstrate biosimilarity with regard to the total and maximum pharmacodynamic response during one dosing interval (AUC GIR.0-24h, GIR max) of Gan & Lee Insulin Glargine with Lantus® (US RLD / EU RP) in subjects with type 1 diabetes Secondary objectives: To compare the pharmacokinetic and pharmacodynamic properties of Gan & Lee Insulin Glargine and of Lantus® (US RLD / EU RP) To assess the safety and tolerability of Gan & Lee Insulin Glargine and of Lantus® (US RLD / EU RP)
Interventions
All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.
Sponsors
Gan and Lee Pharmaceuticals, USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
The trial will be a randomized, double-blind, multicenter, single-dose, 3-way crossover, 3-treatment, euglycemic glucose clamp trial in male subjects with type 1 diabetes mellitus
Eligibility
Sex/Gender
MALE
Age
18 Years to 64 Years
Healthy volunteers
No
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). * Male subjects with type 1 diabetes mellitus for at least 12 months prior to screening as diagnosed clinically. * Age between 18 and 64 years, both inclusive. * Body Mass Index (BMI) between 18.5 and 29.0 kg/m\^2, both inclusive. * HbA1c \<= 9.0%. * Fasting negative C-peptide (\<= 0.30 nmol/L). * Total insulin dose of \< 1.2 (I)U/kg/day. * Stable insulin regimen for at least 2 months prior to screening (with respect to safety of the subject and scientific integrity of the trial). * Considered generally healthy (apart from type 1 diabetes mellitus) upon completion of medical history, physical examination, vital signs, ECG and analysis of laboratory safety variables, as judged by the Investigator
Exclusion criteria
* Known or suspected hypersensitivity to IMPs or related products * Previous participation in this trial. Participation is defined as randomized * Receipt of any medicinal product in clinical development within 30 days or 5 half-lives (whichever is longer) before randomization in this trial * History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction * 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 comorbidity (with the exception of conditions associated with diabetes mellitus), or signs of acute illness, as judged by the Investigator * Proliferative retinopathy or maculopathy (based on a recent (\<1.5 years) ophthalmologic examination) and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator * Recurrent severe hypoglycemia (more than 1 severe hypoglycemic event during the past 6 months) or hypoglycemic unawareness as judged by the Investigator * 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 * Significant history of alcoholism or drug abuse as judged by the Investigator or consuming more than 24 grams alcohol/day * Symptomatic hypotension or supine blood pressure at screening (after resting for at least 5 min in supine position) outside the range of 90-140 mmHg for systolic or greater than 90 mmHg for diastolic pressure * Heart rate at rest outside the range of 50-90 beats per minute * Clinically significant abnormal standard 12-lead ECG after 5 minutes resting in supine position at screening, as judged by the Investigator * A positive result in the alcohol and/or urine drug screen at the screening visit * Not able or willing to refrain from smoking and use of nicotine substitute products one day before and during the inpatient period * 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 * Any medication (prescription and non-prescription drugs) within 14 days before IMP administration, with the exception of occasional use of Paracetamol or NSAIDs * Blood donation or blood loss of more than 500 mL within the last 3 months * Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation * Fertile male with female partner(s) without using a highly effective contraceptive method in combination with spermicide-coated condoms from the first dosing until 1 month after dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK endpoint | Up to 24 hours | AUCins. 0 - 24h, area under the serum insulin concentration curve from 0 to 24. hours |
| PD endpoint | Up to 24 hours | AUC GIR.0-24h, area under the glucose infusion rate curve from 0 to 24 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary PD endpoint | Up to 24 hrs | AUC GIR.0 - 12h, AUC GIR.12 - 24h, areas under the glucose infusion rate curve in the indicated time-intervals |
| Secondary PK endpoint | Up to 24 hrs | AUC ins.0-12h, AUC ins.12 - 24h, AUC ins.0 -inf., areas under the serum insulin concentration curve in the indicated time intervals |
| Safety endpoints | Up to 12 Weeks | As measured by treatment-emergent adverse events |
| Exploratory PD endpoint | Up to 30 hrs | Duration of action, time until blood glucose levels is consistently above 150 mg/dL |
| Exploratory PK endpoint | Up to 30 hrs | t½, terminal serum elimination half-life calculated as t½=ln2/λz and |
Countries
Germany
Outcome results
None listed