Clinical trial NCT04236895: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 1
Keywords: Diabetes
Diabetes Type 1
Type 1
Basal
Insulin
Glargine
T1DM
Diabetes Mellitus
Insulin Dependent Diabetes
Lead sponsor: Gan and Lee Pharmaceuticals, USA
Sponsor class: INDUSTRY
First posted: 2020-01-22
Enrollment: 114
Sex: MALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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 mellitus
Primary purpose: TREATMENT

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)


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

Primary outcomes:
measure: PK endpoint
timeFrame: Up to 24 hours
measure: PK endpoint
timeFrame: Up to 30 hrs
measure: PD endpoint
timeFrame: Up to 24 hours
measure: PD endpoint
timeFrame: Up to 30 hrs
Secondary outcomes:
measure: Secondary PK endpoint
timeFrame: Up to 24 hrs
measure: Secondary PK endpoint
timeFrame: Up to 30 hrs
measure: Exploratory PK endpoint
timeFrame: Up to 30 hrs
measure: Exploratory PK endpoint
timeFrame: Up to 30 hrs
measure: Secondary PD endpoint
timeFrame: Up to 24 hrs
measure: Secondary PD endpoint
timeFrame: Up to 30 hrs
measure: Secondary PD endpoint
timeFrame: Up to 30 hrs
measure: Exploratory PD endpoint
timeFrame: Up to 30 hrs
measure: Exploratory PD endpoint
timeFrame: Up to 30 hrs
measure: Safety endpoints
timeFrame: Up to 12 Weeks
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: Profil Mainz GmbH & Co. KG
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
Study officials:
affiliation: Gan & Lee Pharmaceuticals, USA
name: Jia Lu, PhD
role: STUDY_DIRECTOR
affiliation: Profil Mainz GmbH & Co KG
name: Leona Plum - Mörschel, MD, PD
role: PRINCIPAL_INVESTIGATOR
References: