Single Dose Pharmacokinetic Study of GB221 in Comparison With Herceptin ®

Study Overview
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Brief Summary
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This is a single center, randomized, blind, parallel controlled clinical trial. The primary objective is to evaluate the single dose pharmacokinetics of recombinant Humanized anti-HER-2 monoclonal antibody injection GB221 in comparison with Herceptin ® in Chinese healthy adult volunteers. The main aim is to study the pharmacokinetic similarity between GB221 and Herceptin ®.

Detailed Description
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Subjects will enroll in random order, and be divided into two groups, then receive a single dose (6 mg/kg) of GB221 or Herceptin ®, and accept observation for 42 days. Throughout the course, safety data will be collected.

Official Title
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A Single Center, Randomized, Blind, Parallel Controlled, Single Dose Pharmacokinetic Study of Recombinant Humanized Anti-HER-2 Monoclonal Antibody Injection GB221 in Comparison With Herceptin ® in Chinese Healthy Adult Volunteers

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: GB221
* Drug: Herceptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Signed informed consent form; 2. Healthy adult volunteers aged between 18 and 45, male or female; 3. Medical examination as required within 28 days, body mass index (BMI) 19.0   24.0, weight≥50 kg for men, ≥45 kg for women, and≤ 75 kg for both; 4. Agreed with taking reliable contraceptive measures, and no fertility planning from the beginning to the end of the study within 6 months; 5.Subject can communicate well with the investigators and complete the study according to the study regulations. Exclusion Criteria: 1. Pregnant or lactating women, or positive in either blood or urine pregnancy test; or unwilling to take effective contraceptive measures during the trial and within 6 months after the end of the trial at fertile age; 2. Allergic constitution; or history of allergic to experimental drug ingredient or any drug or food or pollen; or abnormal serum immunoglobulin E (IgE) test; 3. History of drug abuse, or positive urine test for drug; 4. History of the central nervous system, cardiovascular system, kidney, liver, digestive system, respiratory system, metabolic system or other significant diseases. History of high blood pressure, or clinically significant systolic blood pressure≥140 mmHg/diastolic blood pressure≥90 mmHg; 5. Family history of cancer, or tumor markers (male: CEA, AFP, PSA, CA-125; Female: CEA, AFP, CA-153, CA-125) positive. 6. Participated in other clinical trials of drug or used drugs harmful to major organs within 3 months; 7. Blood donation within 3 months; 8. Used prescription or OTC drugs within 14 days; 9. Left ventricular ejection fraction (LVEF) < 60%; 10. ALT or AST > 1.5 ULN, Cr > ULN; 11. WBC < 0.8 LLN or > 1.2 ULN; ANC < 0.8 LLN; PLT < 0.8 LLN; HGB < 0.9LLN. 12. HBs-Ag, HCV-Ab, anti-HIV or TP-Ab positive; 13. Anti-drug antibody (ADA) test positive; 14.History of psychosis; 15. History of postural hypotension; 16. More than 5 cigarettes per day; 17. More than 28 units of alcohol per week; Or alcohol breath test positive within 24 hours before pre-dose; 18. History of dizziness of blood or needle; 19. Unsuitable for other reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GB221 group<br>6 mg/kg, single dose, intravenous infusion, 90-100 min | Drug: GB221<br>* 6 mg/kg, single dose, intravenous infusion, 90-100 min<br>|
| Active Comparator: Herceptin group<br>6 mg/kg, single dose, intravenous infusion, 90-100 min | Drug: Herceptin<br>* 6 mg/kg, single dose, intravenous infusion, 90-100 min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t | compare the pharmacokinetic AUC0-t parameters of GB221 and Herceptin ® | Day 43 | 
| AUC0-∞ | compare the pharmacokinetic AUC0-∞parameters of GB221 and Herceptin ® | Day 43 | 
| Cmax | compare the pharmacokinetic Cmax parameters of GB221 and Herceptin ® | Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | compare the pharmacokinetic Tmax parameters of GB221 and Herceptin ® | Day 43 | 
| t1/2 | compare the pharmacokinetic t1/2 parameters of GB221 and Herceptin ® | Day 43 | 
| CL | compare the pharmacokinetic CL parameters of GB221 and Herceptin ® | Day 43 | 
| Vd | compare the pharmacokinetic Vd parameters of GB221 and Herceptin ® | Day 43 | 
| Ke | compare the pharmacokinetic Ke parameters of GB221 and Herceptin ® | Day 43 | 
| ADA | compare the incidence of ADA in of GB221 and Herceptin ® group | Day 43 | 
| Nab | compare the incidence of Nab in of GB221 and Herceptin ® group | Day 43 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Herceptin, GB221, Breast cancer, Pharmacokinetics, anti-HER-2 human monoclonal antibody