PK/PD Biosimilarity Study of Gan & Lee Insulin Lispro Injection vs. EU and US Humalog® in Healthy Males

A Glucose Clamp Trial Investigating the Biosimilarity of Gan & Lee Insulin Lispro Injection With Both EU - Approved and US - Licensed Humalog® in Healthy Male Subjects

Primary objective:

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

Secondary objectives:

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

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

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Gan & Lee Insulin Lispro Injection

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

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany, 55116
    • Profil Mainz GmbH & Co. KG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• 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 <= 5.5 mmol/L (100 mg/dL) at screening
6. Considered generally healthy upon completion of medical history and screening safety assessments, as judged by the Investigator

Exclusion Criteria:

1. Known or suspected hypersensitivity to IMP(s) or related product
2. Previous participation in this trial. Participation is defined as randomized
3. Receipt of any medicinal product in clinical development within 30 days before randomization in this trial
4. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction
5. Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the Investigator
6. Any history or presence of clinically relevant comorbidity, as judged by the Investigator
7. Signs of acute illness as judged by the Investigator
8. Any serious systemic infectious disease during four weeks prior to first dosing of the trial drug, as judged by the Investigator
9. Clinically significant abnormal screening laboratory tests, as judged by the Investigator
10. Elevation of serum ALT> 10% above the ULN, or elevation of serum AST or serum bilirubin >20% above the ULN. (Note: Elevation of bilirubin is considered acceptable in case of Gilbert's disease and should be evaluated in clinical context)
11. Elevation of serum creatinine > ULN, or elevation of serum urea > 10% above ULN
12. Systolic blood pressure < 90 mmHg or >139 mmHg and/or diastolic blood pressure < 50 mmHg or > 89 mmHg (one repeat test will be acceptable in case of suspected white-coat hypertension)
13. Symptoms of arterial hypotension
14. Heart rate at rest outside the range of 50-90 beats per minute
15. Clinically significant abnormal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position at screening, as judged by the Investigator
16. 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
17. Significant history of alcoholism or drug abuse as judged by the Investigator or consuming more than 24 grams alcohol/day (on average)
18. A positive result in the alcohol and/or urine drug screen at the screening visit
19. Smoking more than 5 cigarettes or the equivalent per day
20. Inability or unwillingness to refrain from smoking and use of nicotine substitute products one day before and during the inpatient period
21. Positive test for Hepatitis Bs antigen
22. Positive test for Hepatitis C antibodies. (Presence of Hepatitis C antibodies will not lead to exclusion if liver function tests are normal and a hepatitis C polymerase chain reaction is negative)
23. Positive result to the test for HIV-1/2 antibodies or HIV-1 antigen
24. Any medication (prescription and non-prescription drugs) within 7 days before IMP administration and/or anticoagulant therapy
25. Blood donation or blood loss of more than 500mL within the last 3 months
26. Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation

Explanatory note on Exclusion Criterion 24: With the exception of paracetamol or NSAIDs for occasional use to treat acute pain, as judged by the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gan & Lee Insulin Lispro Injection; Insulin lispro, 3 mL cartridge in prefilled pen, 100 units/mL (U-100)	Drug: Gan & Lee Insulin Lispro Injection; All three IMPs will be administered as a 0.2 U/kg single dose subcutaneously in the periumbilical area by use of a disposable prefilled pen.; Other Names: EU - approved Humalog ®; US - licensed Humalog ®
Active Comparator: EU - approved Humalog ®; Insulin lispro (product approved and marketed in the EU), 3 mL cartridge in prefilled Kwikpen®, 100 units/mL (U-100)	Drug: Gan & Lee Insulin Lispro Injection; All three IMPs will be administered as a 0.2 U/kg single dose subcutaneously in the periumbilical area by use of a disposable prefilled pen.; Other Names: EU - approved Humalog ®; US - licensed Humalog ®
Active Comparator: US - licensed Humalog ®; Insulin lispro (product approved and marketed in the US), 3 mL cartridge in prefilled Kwikpen®, 100 units/mL (U-100)	Drug: Gan & Lee Insulin Lispro Injection; All three IMPs will be administered as a 0.2 U/kg single dose subcutaneously in the periumbilical area by use of a disposable prefilled pen.; Other Names: EU - approved Humalog ®; US - licensed Humalog ®

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 to 12 hours
Cins.max	PK Endpoint: The maximum observed insulin concentration.	0 to 12 hours
AUCGIR.0-12h	PD endpoint: The area under the glucose infusion rate curve from 0 to 12 hours.	0 to 12 hours
GIRmax	PD endpoint: The maximum glucose infusion rate.	0 to 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 to 2 hours
AUCins.0-4h	PK endpoint: The area under the insulin concentration curve from 0 to 4 hours	0 to 4 hours
AUCins.0-6h	PK endpoint: The area under the insulin concentration curve from 0 to 6 hours	0 to 6 hours
AUCins.6-12h	PK endpoint: The area under the insulin concentration curve from 0 to 12 hours	6 to 12 hours
AUCins.0-∞	PK endpoint: The area under the insulin concentration-time curve from 0 hours to infinity	0 to 12 hours
tins.max	PK endpoint: The time to maximum observed insulin concentration t½, terminal serum elimination half-life calculated as t½=ln2/λz	0 to 12 hours
t50%-ins(early)	PK endpoint: The time to half-maximum insulin concentration before Cins.max	0 to 12 hours
t50%-ins(late)	PK endpoint: The time to half-maximum insulin concentration after Cins.max	0 to 12 hours
t½	PK endpoint: The terminal serum elimination half-life calculated as t½=ln2/λz	0 to 12 hours
λz	PK endpoint: The terminal elimination rate constant of insulin	0 to 12 hours
AUCGIR.0-2h	PD endpoint: The area under the glucose infusion rate curve from 0 to 2 hours	0 to 2 hours
AUCGIR.0-4h	PD endpoint: The area under the glucose infusion rate curve from 0 to 4 hours	0 to 4 hours
AUCGIR.0-6h	PD endpoint: The area under the glucose infusion rate curve from 0 to 6 hours	0 to 6 hours
AUCGIR.6-12h	PD endpoint: The area under the glucose infusion rate curve from 6 to 12 hours	6 to 12 hours
tGIR.max	PD endpoint: The time to maximum glucose infusion rate	0 to 12 hours
tGIR.50%-early	PD endpoint: The time to half-maximum glucose infusion rate before GIRmax	0 to 12 hours
tGIR.50%-late	PD endpoint: The time to half-maximum glucose infusion rate after GIRmax	0 to 12 hours
PD endpoint	time to onset of action	0 to 12 hours
Safety and Local Tolerability	Number of participants experiencing treatment-emergent adverse events	0 to 12 hours

Collaborators and Investigators

• Sponsor: Gan and Lee Pharmaceuticals, USA
• Investigators: Study Director: Jia Lu, PhD, Gan & Lee Pharmaceuticals, USA; Principal Investigator: Leona Plum - Mörschel, Dr. med, Profil Mainz GmbH & Co KG

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2019
• Primary Completion (Actual): July 3, 2019
• Study Completion (Actual): July 3, 2019

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 17, 2020
• First Posted (Actual): January 21, 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; Lispro; Basal; Bolus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Lispro
• Other Study ID Numbers: GL - LSP - 1006

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
• product manufactured in and exported from the U.S.: No