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

Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04235439
• Other study ID #: GL - LSP - 1006
• Status: Completed
• Phase: Phase 1
• Start date: April 23, 2019
• Est. completion date: July 3, 2019

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 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: July 3, 2019
• Est. primary completion date: July 3, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus

Intervention

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.

Locations

Country	Name	City	State
Germany	Profil Mainz GmbH & Co. KG	Mainz

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	AUCins.0-12h	PK Endpoint: The area under the insulin concentration curve from 0 to 12 hours.	0 to 12 hours
Primary	Cins.max	PK Endpoint: The maximum observed insulin concentration.	0 to 12 hours
Primary	AUCGIR.0-12h	PD endpoint: The area under the glucose infusion rate curve from 0 to 12 hours.	0 to 12 hours
Primary	GIRmax	PD endpoint: The maximum glucose infusion rate.	0 to 12 hours
Secondary	AUCins.0-2h	PK endpoint: The area under the insulin concentration curve from 0 to 2 hours	0 to 2 hours
Secondary	AUCins.0-4h	PK endpoint: The area under the insulin concentration curve from 0 to 4 hours	0 to 4 hours
Secondary	AUCins.0-6h	PK endpoint: The area under the insulin concentration curve from 0 to 6 hours	0 to 6 hours
Secondary	AUCins.6-12h	PK endpoint: The area under the insulin concentration curve from 0 to 12 hours	6 to 12 hours
Secondary	AUCins.0-8	PK endpoint: The area under the insulin concentration-time curve from 0 hours to infinity	0 to 12 hours
Secondary	tins.max	PK endpoint: The time to maximum observed insulin concentration t½, terminal serum elimination half-life calculated as t½=ln2/?z	0 to 12 hours
Secondary	t50%-ins(early)	PK endpoint: The time to half-maximum insulin concentration before Cins.max	0 to 12 hours
Secondary	t50%-ins(late)	PK endpoint: The time to half-maximum insulin concentration after Cins.max	0 to 12 hours
Secondary	t½	PK endpoint: The terminal serum elimination half-life calculated as t½=ln2/?z	0 to 12 hours
Secondary	?z	PK endpoint: The terminal elimination rate constant of insulin	0 to 12 hours
Secondary	AUCGIR.0-2h	PD endpoint: The area under the glucose infusion rate curve from 0 to 2 hours	0 to 2 hours
Secondary	AUCGIR.0-4h	PD endpoint: The area under the glucose infusion rate curve from 0 to 4 hours	0 to 4 hours
Secondary	AUCGIR.0-6h	PD endpoint: The area under the glucose infusion rate curve from 0 to 6 hours	0 to 6 hours
Secondary	AUCGIR.6-12h	PD endpoint: The area under the glucose infusion rate curve from 6 to 12 hours	6 to 12 hours
Secondary	tGIR.max	PD endpoint: The time to maximum glucose infusion rate	0 to 12 hours
Secondary	tGIR.50%-early	PD endpoint: The time to half-maximum glucose infusion rate before GIRmax	0 to 12 hours
Secondary	tGIR.50%-late	PD endpoint: The time to half-maximum glucose infusion rate after GIRmax	0 to 12 hours
Secondary	PD endpoint	time to onset of action	0 to 12 hours
Secondary	Safety and Local Tolerability	Number of participants experiencing treatment-emergent adverse events	0 to 12 hours