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

Diabetes Mellitus, Type 1 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04236895
• Other study ID #: GL-GLA-CT1002
• Status: Completed
• Phase: Phase 1
• Start date: July 10, 2018
• Est. completion date: November 28, 2018

Study information

• Verified date: January 2020
• Source: Gan and Lee Pharmaceuticals, USA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: November 28, 2018
• Est. primary completion date: November 28, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

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.

Locations

Country	Name	City	State
Germany	Profil Mainz GmbH & Co. KG	Mainz
Germany	Profil Institut für Stoffwechselforschung GmbH	Neuss

Sponsors (1)

Lead Sponsor	Collaborator
Gan and Lee Pharmaceuticals, USA

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK endpoint	AUCins. 0 - 24h, area under the serum insulin concentration curve from 0 to 24. hours	Up to 24 hours
Primary	PK endpoint	Cins.max, maximum observed insulin concentration.	Up to 30 hrs
Primary	PD endpoint	AUC GIR.0-24h, area under the glucose infusion rate curve from 0 to 24 hours.	Up to 24 hours
Primary	PD endpoint	GIR max, maximum observed glucose infusion rate	Up to 30 hrs
Secondary	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	Up to 24 hrs
Secondary	Secondary PK endpoint	tmax.ins, time to maximum observed serum insulin concentration	Up to 30 hrs
Secondary	Exploratory PK endpoint	t½, terminal serum elimination half-life calculated as t½=ln2/?z and	Up to 30 hrs
Secondary	Exploratory PK endpoint	?z, terminal elimination rate constant	Up to 30 hrs
Secondary	Secondary PD endpoint	AUC GIR.0 - 12h, AUC GIR.12 - 24h, areas under the glucose infusion rate curve in the indicated time-intervals	Up to 24 hrs
Secondary	Secondary PD endpoint	AUC GIR.0 - last, area under the glucose infusion rate curve from 0 hours until the end of clamp	Up to 30 hrs
Secondary	Secondary PD endpoint	t max.GIR, time to maximum glucose infusion rate	Up to 30 hrs
Secondary	Exploratory PD endpoint	Duration of action, time until blood glucose levels is consistently above 150 mg/dL	Up to 30 hrs
Secondary	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.	Up to 30 hrs
Secondary	Safety endpoints	As measured by treatment-emergent adverse events	Up to 12 Weeks