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

NCT04236895 | Completed Phase 1 FDA Drug

• 1 other identifier: GL-GLA-CT1002
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 2

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)

Conditions

Diabetes Mellitus, Type 1

Keywords

Diabetes; Diabetes Type 1; Type 1; Basal; Insulin; Glargine; T1DM; Diabetes Mellitus; Insulin Dependent Diabetes

Outcome Measures

Primary Outcomes (4)

• PK endpoint

  AUCins. 0 - 24h, area under the serum insulin concentration curve from 0 to 24. hours

  Up to 24 hours

• PK endpoint

  Cins.max, maximum observed insulin concentration.

  Up to 30 hrs

• PD endpoint

  AUC GIR.0-24h, area under the glucose infusion rate curve from 0 to 24 hours.

  Up to 24 hours

• PD endpoint

  GIR max, maximum observed glucose infusion rate

  Up to 30 hrs

Secondary Outcomes (10)

• Secondary PK endpoint

  Up to 24 hrs

• Secondary PK endpoint

  Up to 30 hrs

• Exploratory PK endpoint

  Up to 30 hrs

• Exploratory PK endpoint

  Up to 30 hrs

• Secondary PD endpoint

  Up to 24 hrs

Study Arms (3)

Lantus ® US

ACTIVE COMPARATOR

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

Lantus ® EU

ACTIVE COMPARATOR

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

Drug: Gan & Lee Insulin Glargine Injection

Gan & Lee Insulin Glargine

EXPERIMENTAL

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

Drug: Gan & Lee Insulin Glargine Injection

Interventions

Gan & Lee Insulin Glargine Injection DRUG

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

Gan & Lee Insulin Glargine; Lantus ® EU; Lantus ® US

Eligibility Criteria

• Age: 18 Years - 64 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gan and Lee Pharmaceuticals, USA: lead

Study Sites (2)

Profil Mainz GmbH & Co. KG

Mainz, 55116, Germany

Location

Profil Institut für Stoffwechselforschung GmbH

Neuss, 41460, Germany

Location

Related Publications (1)

• Chen W, Lu J, Plum-Morschel L, Andersen G, Zijlstra E, He A, Xie T, Li L, Hao C, Gan Z, Heise T. Pharmacokinetic and pharmacodynamic bioequivalence of Gan & Lee insulin analogues aspart (rapilin(R)), lispro (prandilin(R)) and glargine (basalin(R)) with EU- und US-sourced reference insulins. Diabetes Obes Metab. 2023 Dec;25(12):3817-3825. doi: 10.1111/dom.15281. Epub 2023 Sep 21.

  PMID: 37735841 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Insulin Resistance

Interventions

gallium nitrate

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Study Officials

• Jia Lu, PhD

  Gan & Lee Pharmaceuticals, USA

  STUDY DIRECTOR

• Leona Plum - Mörschel, MD, PD

  Profil Mainz GmbH & Co KG

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: January 15, 2020
• First Posted: January 22, 2020
• Study Start: July 10, 2018
• Primary Completion: November 28, 2018
• Study Completion: November 28, 2018
• Last Updated: January 22, 2020

Record last verified: 2020-01

Locations

DE (2)