Diabetes Mellitus
Conditions
Keywords
Diabetes, Insulin, Lispro, Diabetes Mellitus, Basal, Bolus
Brief summary
Primary objective: To demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of Gan & Lee Insulin Lispro Injection with both EU - approved Humalog® and US - licensed Humalog® (Reference Products) in healthy male subjects Secondary objectives: To compare the PK and PD parameters of the three insulin lispro preparations To evaluate the single dose safety and local tolerability of the three insulin lispro preparations
Interventions
All three IMPs will be administered as a 0.2 U/kg single dose subcutaneously in the periumbilical area by use of a disposable prefilled pen.
Sponsors
Gan and Lee Pharmaceuticals, USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This is a phase 1 trial. The trial is a single center, randomized, doubleblind, single dose, there treatment, three period crossover, 12 - hour euglycaemic glucose clamp trial in healthy male subjects.
Eligibility
Sex/Gender
MALE
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
1. Signed and dated informed consent obtained before any trial related activities. Trial related activities are any procedures that would not have been done during normal management of the subject 2. Healthy male subjects 3. Age between 18 and 64 years, both inclusive 4. Body Mass Index (BMI) between 18.5 and 29.0 kg/m\^2, both inclusive 5. Fasting plasma glucose concentration \<= 5.5 mmol/L (100 mg/dL) at screening 6. Considered generally healthy upon completion of medical history and screening safety assessments, as judged by the Investigator
Exclusion criteria
1. Known or suspected hypersensitivity to IMP(s) or related product 2. Previous participation in this trial. Participation is defined as randomized 3. Receipt of any medicinal product in clinical development within 30 days before randomization in this trial 4. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction 5. Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the Investigator 6. Any history or presence of clinically relevant comorbidity, as judged by the Investigator 7. Signs of acute illness as judged by the Investigator 8. Any serious systemic infectious disease during four weeks prior to first dosing of the trial drug, as judged by the Investigator 9. Clinically significant abnormal screening laboratory tests, as judged by the Investigator 10. Elevation of serum ALT\> 10% above the ULN, or elevation of serum AST or serum bilirubin \>20% above the ULN. (Note: Elevation of bilirubin is considered acceptable in case of Gilbert's disease and should be evaluated in clinical context) 11. Elevation of serum creatinine \> ULN, or elevation of serum urea \> 10% above ULN 12. Systolic blood pressure \< 90 mmHg or \>139 mmHg and/or diastolic blood pressure \< 50 mmHg or \> 89 mmHg (one repeat test will be acceptable in case of suspected white-coat hypertension) 13. Symptoms of arterial hypotension 14. Heart rate at rest outside the range of 50-90 beats per minute 15. Clinically significant abnormal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position at screening, as judged by the Investigator 16. 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 17. Significant history of alcoholism or drug abuse as judged by the Investigator or consuming more than 24 grams alcohol/day (on average) 18. A positive result in the alcohol and/or urine drug screen at the screening visit 19. Smoking more than 5 cigarettes or the equivalent per day 20. Inability or unwillingness to refrain from smoking and use of nicotine substitute products one day before and during the inpatient period 21. Positive test for Hepatitis Bs antigen 22. Positive test for Hepatitis C antibodies. (Presence of Hepatitis C antibodies will not lead to exclusion if liver function tests are normal and a hepatitis C polymerase chain reaction is negative) 23. Positive result to the test for HIV-1/2 antibodies or HIV-1 antigen 24. Any medication (prescription and non-prescription drugs) within 7 days before IMP administration and/or anticoagulant therapy 25. Blood donation or blood loss of more than 500mL within the last 3 months 26. Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation Explanatory note on Exclusion Criterion 24: With the exception of paracetamol or NSAIDs for occasional use to treat acute pain, as judged by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUCins.0-12h | 0 to 12 hours | PK Endpoint: The area under the insulin concentration curve from 0 to 12 hours. |
| Cins.max | 0 to 12 hours | PK Endpoint: The maximum observed insulin concentration. |
| AUCGIR.0-12h | 0 to 12 hours | PD endpoint: The area under the glucose infusion rate curve from 0 to 12 hours. |
| GIRmax | 0 to 12 hours | PD endpoint: The maximum glucose infusion rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUCins.0-∞ | 0 to 12 hours | PK endpoint: The area under the insulin concentration-time curve from 0 hours to infinity |
| tins.max | 0 to 12 hours | PK endpoint: The time to maximum observed insulin concentration t½, terminal serum elimination half-life calculated as t½=ln2/λz |
| t50%-ins(early) | 0 to 12 hours | PK endpoint: The time to half-maximum insulin concentration before Cins.max |
| t50%-ins(late) | 0 to 12 hours | PK endpoint: The time to half-maximum insulin concentration after Cins.max |
| t½ | 0 to 12 hours | PK endpoint: The terminal serum elimination half-life calculated as t½=ln2/λz |
| λz | 0 to 12 hours | PK endpoint: The terminal elimination rate constant of insulin |
| AUCGIR.0-2h | 0 to 2 hours | PD endpoint: The area under the glucose infusion rate curve from 0 to 2 hours |
| AUCins.0-2h | 0 to 2 hours | PK endpoint: The area under the insulin concentration curve from 0 to 2 hours |
| AUCGIR.0-6h | 0 to 6 hours | PD endpoint: The area under the glucose infusion rate curve from 0 to 6 hours |
| AUCGIR.6-12h | 6 to 12 hours | PD endpoint: The area under the glucose infusion rate curve from 6 to 12 hours |
| tGIR.max | 0 to 12 hours | PD endpoint: The time to maximum glucose infusion rate |
| tGIR.50%-early | 0 to 12 hours | PD endpoint: The time to half-maximum glucose infusion rate before GIRmax |
| tGIR.50%-late | 0 to 12 hours | PD endpoint: The time to half-maximum glucose infusion rate after GIRmax |
| PD endpoint | 0 to 12 hours | time to onset of action |
| Safety and Local Tolerability | 0 to 12 hours | Number of participants experiencing treatment-emergent adverse events |
| AUCGIR.0-4h | 0 to 4 hours | PD endpoint: The area under the glucose infusion rate curve from 0 to 4 hours |
| AUCins.0-4h | 0 to 4 hours | PK endpoint: The area under the insulin concentration curve from 0 to 4 hours |
| AUCins.0-6h | 0 to 6 hours | PK endpoint: The area under the insulin concentration curve from 0 to 6 hours |
| AUCins.6-12h | 6 to 12 hours | PK endpoint: The area under the insulin concentration curve from 0 to 12 hours |
Countries
Germany
Outcome results
None listed