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

• ClinicalTrials.gov Identifier: NCT04235439
• Recruitment Status: Completed
• First Posted: January 20, 2020
• Last Update Posted: January 20, 2020
• Sponsor: Gan and Lee Pharmaceuticals, USA
• Information provided by (Responsible Party): Gan and Lee Pharmaceuticals, USA

Tracking Information

• First Submitted Date: January 15, 2020
• First Posted Date: January 20, 2020
• Last Update Posted Date: January 20, 2020
• Actual Study Start Date: April 23, 2019
• Actual Primary Completion Date: July 3, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 17, 2020)

• PK endpoint [ Time Frame: 20-68 days ]
  AUCins.0-12h, area under the insulin concentration curve from 0 to 12 hours
• PK endpoint [ Time Frame: 20-68 days ]
  Cins.max, maximum observed insulin concentration
• PD endpoint [ Time Frame: 20-68 days ]
  AUCGIR.0-12h, area under the glucose infusion rate curve from 0 to 12 hours
• PD endpoint [ Time Frame: 20-68 days ]
  GIRmax, maximum glucose infusion rate

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: January 17, 2020)

• PK endpoint [ Time Frame: Up to Day 68 ]
  AUCins.0-2h, area under the insulin concentration curve from 0 to 2 hours
• PK endpoint [ Time Frame: Up to Day 68 ]
  AUCins.0-4h, area under the insulin concentration curve from 0 to 4 hours
• PK endpoint [ Time Frame: Up to Day 68 ]
  AUCins.0-6h, area under the insulin concentration curve from 0 to 6 hours
• PK endpoint [ Time Frame: Up to Day 68 ]
  AUCins.0-12h, area under the insulin concentration curve from 0 to 12 hours
• PK endpoint [ Time Frame: Up to Day 68 ]
  AUCins.0-∞, area under the insulin concentration-time curve from 0 hours to infinity
• PK endpoint [ Time Frame: Up to Day 68 ]
  tins.max, time to maximum observed insulin concentration t½, terminal serum elimination half-life calculated as t½=ln2/λz
• PK endpoint [ Time Frame: Up to Day 68 ]
  t50%-ins(early), time to half-maximum insulin concentration before Cins.max
• PK endpoint [ Time Frame: Up to Day 68 ]
  t50%-ins(late), time to half-maximum insulin concentration after Cins.max
• PK endpoint [ Time Frame: Up to Day 68 ]
  t½, terminal serum elimination half-life calculated as t½=ln2/λz
• PK endpoint [ Time Frame: Up to Day 68 ]
  λz, terminal elimination rate constant of insulin
• PD endpoint [ Time Frame: Up to Day 68 ]
  AUCGIR.0-2h, area under the glucose infusion rate curve from 0 to 2 hours
• PD endpoint [ Time Frame: Up to Day 68 ]
  AUCGIR.0-4h, area under the glucose infusion rate curve from 0 to 4 hours
• PD endpoint [ Time Frame: Up to Day 68 ]
  AUCGIR.0-6h, area under the glucose infusion rate curve from 0 to 6 hours
• PD endpoint [ Time Frame: Up to Day 68 ]
  AUCGIR.6-12h, area under the glucose infusion rate curve from 6 to 12 hours
• PD endpoint [ Time Frame: Up to Day 68 ]
  tGIR.max, time to maximum glucose infusion rate
• PD endpoint [ Time Frame: Up to Day 68 ]
  tGIR.50%-early, time to half-maximum glucose infusion rate before GIRmax
• PD endpoint [ Time Frame: Up to Day 68 ]
  tGIR.50%-late, time to half-maximum glucose infusion rate after GIRmax
• PD endpoint [ Time Frame: Up to Day 68 ]
  time to onset of action
• Safety and Local Tolerability [ Time Frame: Up to Day 68 ]
  Number of participants experiencing treatment-emergent adverse events

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief 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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

This is a phase 1 trial. The trial is a single center, randomized, doubleblind, single dose, there treatment, three period crossover, 12 - hour euglycaemic glucose clamp trial in healthy male subjects.

Masking: Double (Participant, Investigator)
Primary Purpose: Treatment

• Condition: 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.

Other Names:

• EU - approved Humalog ®
• US - licensed Humalog ®

Study Arms

• Experimental: Gan & Lee Insulin Lispro Injection
  Insulin lispro, 3 mL cartridge in prefilled pen, 100 units/mL (U-100)
  Intervention: Drug: Gan & Lee Insulin Lispro Injection
• 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)
  Intervention: Drug: Gan & Lee Insulin Lispro Injection
• 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)
  Intervention: Drug: Gan & Lee Insulin Lispro Injection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 17, 2020): 36
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: July 3, 2019
• Actual Primary Completion Date: July 3, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes

• Ages: 18 Years to 64 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT04235439
• Other Study ID Numbers: GL - LSP - 1006
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Gan and Lee Pharmaceuticals, USA
• Study Sponsor: Gan and Lee Pharmaceuticals, USA
• Collaborators: Not Provided

Investigators

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

• PRS Account: Gan and Lee Pharmaceuticals, USA
• Verification Date: January 2020