PK/PD Biosimilarity Study of Gan & Lee Insulin Glargine Injection vs.US & EU Lantus® in Type 1 Diabetes Mellitus Patients
- Conditions
- Diabetes Mellitus, Type 1
- Interventions
- Drug: Gan & Lee Insulin Glargine Injection
- Registration Number
- NCT04236895
- Lead Sponsor
- Gan and Lee Pharmaceuticals, USA
- 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 114
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Lantus ® US Gan & Lee Insulin Glargine Injection Insulin glargine (Lantus®, product approved and marketed in the USA (US RLD)), 100 U/mL in 3 mL pre-filled pens Gan & Lee Insulin Glargine Gan & Lee Insulin Glargine Injection Insulin glargine 100 U/mL in 3 mL pre-filled pens Lantus ® EU Gan & Lee Insulin Glargine Injection Insulin glargine (Lantus®, product marketed in Germany (EU RP)), 100 U/mL in 3 ml pre-filled pens
- Primary Outcome Measures
Name Time Method PD endpoint Up to 30 hrs GIR max, maximum observed glucose infusion rate
PK endpoint Up to 30 hrs Cins.max, maximum observed insulin concentration.
- Secondary Outcome Measures
Name Time Method Secondary PK endpoint Up to 30 hrs tmax.ins, time to maximum observed serum insulin concentration
Exploratory PK endpoint Up to 30 hrs λz, terminal elimination rate constant
Secondary PD endpoint Up to 30 hrs t max.GIR, time to maximum glucose infusion rate
Safety endpoints Up to 12 Weeks As measured by treatment-emergent adverse events
Exploratory PD endpoint Up to 30 hrs Time to onset of action, time from trial product administration until blood glucose concentration has decreased at least 5 mg/dL from baseline, where baseline is defined as the mean of blood glucose levels from - 6 to - 2 minutes before trial product administration as measured by ClampArt.
Trial Locations
- Locations (2)
Profil Mainz GmbH & Co. KG
🇩🇪Mainz, Germany
Profil Institut für Stoffwechselforschung GmbH
🇩🇪Neuss, Germany