PK/PD Study of Gan & Lee Insulin Aspart Injection vs. US & EU NovoLog®/NovoRapid® in Healthy Males

A Glucose Clamp Trial Investigating The Biosimilarity of Gan & Lee Insulin Aspart Injection (Insulin Aspart 100 U/ml) With US and EU Insulin Aspart Comparator Products (NovoLog®/NovoRapid®) in Healthy Male Subjects

Primary objective:

To demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of Gan & Lee Insulin Aspart Injection with both EU-approved NovoRapid® and US-licensed NovoLog® (Reference Products) in healthy male subjects

Secondary objectives:

To compare the PK and PD parameters of the three insulin aspart preparations

To evaluate the single dose safety and local tolerability of the three insulin aspart preparations

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Gan & Lee Insulin Aspart

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, D-55116
      • Profil Mainz GmbH & Co. KG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Signed and dated informed consent obtained before any trial-related activities. Trial-related activities are any procedures that would not have been done during normal management of the subject
2. Healthy male subjects
3. Age between 18 and 64 years, both inclusive
4. Body Mass Index (BMI) between 18.5 and 29.0 kg/m^2, both inclusive
5. Fasting plasma glucose concentration <= 5.50 mmol/L (100 mg/dL) at screening
6. Considered generally healthy upon completion of medical history, physical examination, vital signs, ECG and analysis of laboratory safety variables, as judged by the Investigator

Exclusion Criteria:

1. Known or suspected hypersensitivity to investigational medicinal products (IMPs) or related product
2. Previous participation in this trial. Participation is defined as randomized
3. Use of other investigational drugs within five half-lives for enrolment or receipt of any medicinal product in clinical development within 30 days before randomization in this trial, whichever is longer
4. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
5. Clinically significant abnormal values for haematology, biochemistry, coagulation, or urinalysis as judged by the Investigator
6. 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
7. A positive result in the alcohol and/or urine drug screen at the screening visit
8. 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
9. Blood donation or blood loss of m ore than 500 mL within the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Gan & Lee Insulin Aspart; 100 units/mL, 3 ml prefilled pen	Drug: Gan & Lee Insulin Aspart; All three IMPs will be administered as a 0.2 U/kg single dose subcutaneously in the periumbilical area.; Other Names: NovoRapid® EU; NovoLog® US
ACTIVE_COMPARATOR: NovoRapid® Insulin Aspart; Product approved and marketed in the EU FlexPen100 units/mL prefilled pen	Drug: Gan & Lee Insulin Aspart; All three IMPs will be administered as a 0.2 U/kg single dose subcutaneously in the periumbilical area.; Other Names: NovoRapid® EU; NovoLog® US
ACTIVE_COMPARATOR: NovoLog® Insulin Aspart; Product approved and marketed in the US FlexPen100 units/mL prefilled pen	Drug: Gan & Lee Insulin Aspart; All three IMPs will be administered as a 0.2 U/kg single dose subcutaneously in the periumbilical area.; Other Names: NovoRapid® EU; NovoLog® US

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCins.0-12h	PK endpoint: The area under the insulin concentration curve from 0 to 12 hours	0 -12 hours
Cins.max	PK endpoint: The maximum observed insulin concentration	0 -12 hours
AUCGIR.0-12h	PD endpoint: The area under the glucose infusion rate curve from 0 to 12 hours	0 - 12 hours
GIRmax	PD endpoint: The maximum glucose infusion rate	0 - 12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCins.0-2h	PK endpoint: The area under the insulin concentration curve from 0 to 2 hours	0 - 2 hours
AUCins.0-∞	PK endpoint: The area under the insulin concentration-time curve from 0 hours to infinity	0 - 12 hours
tins.max	PK endpoint: The time to maximum observed insulin concentration	Up to Day 68
t50%-ins(early)	PK endpoint: The time to half-maximum insulin concentration before Cins.max	Up to Day 68
t50%-ins(late)	PK endpoint: The time to half-maximum insulin concentration after Cins.max	Up to Day 68
t½	PK endpoint: The terminal serum elimination half-life calculated as t½=ln2/λz	Up to Day 68
λz	PK endpoint: The terminal elimination rate constant of insulin	Up to Day 68
AUCGIR.0-2h	PD endpoint: The area under the glucose infusion rate curve from 0 to 2 hours	0 - 2 hours
tGIR.max	PD endpoint: The time to maximum glucose infusion rate	Up to Day 68
tGIR.50%-early	PD endpoint: The time to half-maximum glucose infusion rate before GIRmax	Up to Day 68
tGIR.50%-late	PD endpoint: The time to half-maximum glucose infusion rate after GIRmax	Up to Day 68
PD endpoint	time to onset of action	Up to Day 68
Safety and local tolerability	Number of participants experiencing treatment-emergent adverse events	Up to Day 68

Collaborators and Investigators

• Sponsor: Gan and Lee Pharmaceuticals, USA
• Investigators: Study Director: Matthew E Barton, PhD, Gan & Lee Pharmaceuticals USA Corporation

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 27, 2019
• Primary Completion (ACTUAL): December 16, 2019
• Study Completion (ACTUAL): December 16, 2019

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 17, 2020
• First Posted (ACTUAL): January 23, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Diabetes; Insulin; Diabetes Mellitus; Basal; Bolus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Aspart
• Other Study ID Numbers: GL-ASP-1008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No