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

Sponsor

Gan and Lee Pharmaceuticals, USA (Industry)

Overall Status

Completed

CT.gov ID

NCT04236895

Collaborator

(none)

114

Enrollment

Locations

Arms

4.6

Actual Duration (Months)

Patients Per Site

12.3

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Gan & Lee Insulin Glargine Injection	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

114 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

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 mellitusThe 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

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Glucose Clamp Trial Investigating the Biosimilarity of Gan & Lee Insulin Glargine Injection (Insulin Glargine 100 U/mL) With US and EU Lantus® Comparator Products in Patients With Type 1 Diabetes Mellitus

Actual Study Start Date :

Jul 10, 2018

Actual Primary Completion Date :

Nov 28, 2018

Actual Study Completion Date :

Nov 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lantus ® US Insulin glargine (Lantus®, product approved and marketed in the USA (US RLD)), 100 U/mL in 3 mL pre-filled pens	Drug: Gan & Lee Insulin Glargine Injection All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.
Active Comparator: Lantus ® EU Insulin glargine (Lantus®, product marketed in Germany (EU RP)), 100 U/mL in 3 ml pre-filled pens	Drug: Gan & Lee Insulin Glargine Injection All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.
Experimental: Gan & Lee Insulin Glargine Insulin glargine 100 U/mL in 3 mL pre-filled pens	Drug: Gan & Lee Insulin Glargine Injection All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.

Arm

Intervention/Treatment

Active Comparator: Lantus ® US

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

Drug: Gan & Lee Insulin Glargine Injection

All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.

Active Comparator: Lantus ® EU

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

Drug: Gan & Lee Insulin Glargine Injection

All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.

Experimental: Gan & Lee Insulin Glargine

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

Drug: Gan & Lee Insulin Glargine Injection

All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.

Outcome Measures

Primary Outcome Measures

PK endpoint [Up to 24 hours]
AUCins. 0 - 24h, area under the serum insulin concentration curve from 0 to 24. hours
PK endpoint [Up to 30 hrs]
Cins.max, maximum observed insulin concentration.
PD endpoint [Up to 24 hours]
AUC GIR.0-24h, area under the glucose infusion rate curve from 0 to 24 hours.
PD endpoint [Up to 30 hrs]
GIR max, maximum observed glucose infusion rate

Secondary Outcome Measures

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
Secondary PK endpoint [Up to 30 hrs]
tmax.ins, time to maximum observed serum insulin concentration
Exploratory PK endpoint [Up to 30 hrs]
t½, terminal serum elimination half-life calculated as t½=ln2/λz and
Exploratory PK endpoint [Up to 30 hrs]
λz, terminal elimination rate constant
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 PD endpoint [Up to 30 hrs]
AUC GIR.0 - last, area under the glucose infusion rate curve from 0 hours until the end of clamp
Secondary PD endpoint [Up to 30 hrs]
t max.GIR, time to maximum glucose infusion rate
Exploratory PD endpoint [Up to 30 hrs]
Duration of action, time until blood glucose levels is consistently above 150 mg/dL
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.
Safety endpoints [Up to 12 Weeks]
As measured by treatment-emergent adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

Male

Accepts 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