PK/PD Biosimilarity Study of Gan & Lee Insulin Glargine Injection vs.US & EU Lantus® in Type 1 Diabetes Mellitus Patients

Gan and Lee Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: Gan & Lee Insulin Glargine Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT04236895

GL-GLA-CT1002

Details and patient eligibility

About

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)

Enrollment: 114 patients

Sex: Male

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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114 participants in 3 patient groups

Lantus ® US

Active Comparator group

Description:

Insulin glargine (Lantus®, product approved and marketed in the USA (US RLD)), 100 U/mL in 3 mL pre-filled pens

Treatment:

Drug: Gan & Lee Insulin Glargine Injection

Lantus ® EU

Active Comparator group

Description:

Insulin glargine (Lantus®, product marketed in Germany (EU RP)), 100 U/mL in 3 ml pre-filled pens

Treatment:

Drug: Gan & Lee Insulin Glargine Injection

Gan & Lee Insulin Glargine

Experimental group

Description:

Insulin glargine 100 U/mL in 3 mL pre-filled pens

Treatment:

Drug: Gan & Lee Insulin Glargine Injection