PK/PD Biosimilarity Study of Gan & Lee Insulin Glargine Injection vs.US & EU Lantus® in Type 1 Diabetes Mellitus Patients
Primary Purpose
Diabetes Mellitus, Type 1
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Gan & Lee Insulin Glargine Injection
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Diabetes, Diabetes Type 1, Type 1, Basal, Insulin, Glargine, T1DM, Diabetes Mellitus, Insulin Dependent Diabetes
Eligibility Criteria
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
Sites / Locations
- Profil Mainz GmbH & Co. KG
- Profil Institut für Stoffwechselforschung GmbH
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Experimental
Arm Label
Lantus ® US
Lantus ® EU
Gan & Lee Insulin Glargine
Arm Description
Insulin glargine (Lantus®, product approved and marketed in the USA (US RLD)), 100 U/mL in 3 mL pre-filled pens
Insulin glargine (Lantus®, product marketed in Germany (EU RP)), 100 U/mL in 3 ml pre-filled pens
Insulin glargine 100 U/mL in 3 mL pre-filled pens
Outcomes
Primary Outcome Measures
PK endpoint
AUCins. 0 - 24h, area under the serum insulin concentration curve from 0 to 24. hours
PK endpoint
Cins.max, maximum observed insulin concentration.
PD endpoint
AUC GIR.0-24h, area under the glucose infusion rate curve from 0 to 24 hours.
PD endpoint
GIR max, maximum observed glucose infusion rate
Secondary Outcome Measures
Secondary PK endpoint
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
tmax.ins, time to maximum observed serum insulin concentration
Exploratory PK endpoint
t½, terminal serum elimination half-life calculated as t½=ln2/λz and
Exploratory PK endpoint
λz, terminal elimination rate constant
Secondary PD endpoint
AUC GIR.0 - 12h, AUC GIR.12 - 24h, areas under the glucose infusion rate curve in the indicated time-intervals
Secondary PD endpoint
AUC GIR.0 - last, area under the glucose infusion rate curve from 0 hours until the end of clamp
Secondary PD endpoint
t max.GIR, time to maximum glucose infusion rate
Exploratory PD endpoint
Duration of action, time until blood glucose levels is consistently above 150 mg/dL
Exploratory PD endpoint
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
As measured by treatment-emergent adverse events
Full Information
NCT ID
NCT04236895
First Posted
January 15, 2020
Last Updated
January 17, 2020
Sponsor
Gan and Lee Pharmaceuticals, USA
1. Study Identification
Unique Protocol Identification Number
NCT04236895
Brief Title
PK/PD Biosimilarity Study of Gan & Lee Insulin Glargine Injection vs.US & EU Lantus® in Type 1 Diabetes Mellitus Patients
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
July 10, 2018 (Actual)
Primary Completion Date
November 28, 2018 (Actual)
Study Completion Date
November 28, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gan and Lee Pharmaceuticals, USA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
Keywords
Diabetes, Diabetes Type 1, Type 1, Basal, Insulin, Glargine, T1DM, Diabetes Mellitus, Insulin Dependent Diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
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
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
114 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lantus ® US
Arm Type
Active Comparator
Arm Description
Insulin glargine (Lantus®, product approved and marketed in the USA (US RLD)), 100 U/mL in 3 mL pre-filled pens
Arm Title
Lantus ® EU
Arm Type
Active Comparator
Arm Description
Insulin glargine (Lantus®, product marketed in Germany (EU RP)), 100 U/mL in 3 ml pre-filled pens
Arm Title
Gan & Lee Insulin Glargine
Arm Type
Experimental
Arm Description
Insulin glargine 100 U/mL in 3 mL pre-filled pens
Intervention Type
Drug
Intervention Name(s)
Gan & Lee Insulin Glargine Injection
Intervention Description
All IMPs will be administered as a 0.5 U/kg single subcutaneous dose by a pre-filled pen.
Primary Outcome Measure Information:
Title
PK endpoint
Description
AUCins. 0 - 24h, area under the serum insulin concentration curve from 0 to 24. hours
Time Frame
Up to 24 hours
Title
PK endpoint
Description
Cins.max, maximum observed insulin concentration.
Time Frame
Up to 30 hrs
Title
PD endpoint
Description
AUC GIR.0-24h, area under the glucose infusion rate curve from 0 to 24 hours.
Time Frame
Up to 24 hours
Title
PD endpoint
Description
GIR max, maximum observed glucose infusion rate
Time Frame
Up to 30 hrs
Secondary Outcome Measure Information:
Title
Secondary PK endpoint
Description
AUC ins.0-12h, AUC ins.12 - 24h, AUC ins.0 -inf., areas under the serum insulin concentration curve in the indicated time intervals
Time Frame
Up to 24 hrs
Title
Secondary PK endpoint
Description
tmax.ins, time to maximum observed serum insulin concentration
Time Frame
Up to 30 hrs
Title
Exploratory PK endpoint
Description
t½, terminal serum elimination half-life calculated as t½=ln2/λz and
Time Frame
Up to 30 hrs
Title
Exploratory PK endpoint
Description
λz, terminal elimination rate constant
Time Frame
Up to 30 hrs
Title
Secondary PD endpoint
Description
AUC GIR.0 - 12h, AUC GIR.12 - 24h, areas under the glucose infusion rate curve in the indicated time-intervals
Time Frame
Up to 24 hrs
Title
Secondary PD endpoint
Description
AUC GIR.0 - last, area under the glucose infusion rate curve from 0 hours until the end of clamp
Time Frame
Up to 30 hrs
Title
Secondary PD endpoint
Description
t max.GIR, time to maximum glucose infusion rate
Time Frame
Up to 30 hrs
Title
Exploratory PD endpoint
Description
Duration of action, time until blood glucose levels is consistently above 150 mg/dL
Time Frame
Up to 30 hrs
Title
Exploratory PD endpoint
Description
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.
Time Frame
Up to 30 hrs
Title
Safety endpoints
Description
As measured by treatment-emergent adverse events
Time Frame
Up to 12 Weeks
10. Eligibility
Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jia Lu, PhD
Organizational Affiliation
Gan & Lee Pharmaceuticals, USA
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Leona Plum - Mörschel, MD, PD
Organizational Affiliation
Profil Mainz GmbH & Co KG
Official's Role
Principal Investigator
Facility Information:
Facility Name
Profil Mainz GmbH & Co. KG
City
Mainz
ZIP/Postal Code
55116
Country
Germany
Facility Name
Profil Institut für Stoffwechselforschung GmbH
City
Neuss
ZIP/Postal Code
41460
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
PK/PD Biosimilarity Study of Gan & Lee Insulin Glargine Injection vs.US & EU Lantus® in Type 1 Diabetes Mellitus Patients
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