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Clinical Study to Compare the Pharmacokinetics and Safety of Ramucirumab Injection With Cyramza ® in Healthy Male Volunteers

Primary Purpose

Gastric Cancer, Non-small Cell Lung Cancer, Colo-rectal Cancer

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Ramucirumab Injection
Ramucirumab Injection [Cyramza]
Sponsored by
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria: Sign informed consent form before the study and fully understand the study content, process and possible adverse reactions; Be able to complete the study according to the requirements of the test plan; Male subjects aged 18-65 years (included); The subject should weigh at least 50kg. Body mass index (BMI) = weight (kg)/ height2(m2), BMI in the range of 19 to 26 (included); Health status: no mental abnormality, no medical history of abnormal cardiovascular system, nervous system, respiratory system, digestive system, urinary system, endocrine system and metabolism; Normal or abnormal vital signs, physical examination, laboratory examination, electrocardiogram and imaging examination with no clinical significance; Have no pregnancy plan and voluntarily take effective contraception measures from 2 weeks before the study drug administration to at least 6 months after the last dose. Exclusion Criteria: Have a history of neuropsychiatric system, respiratory system, cardiovascular system, digestive system, hemolymph system, liver and kidney insufficiency, endocrine system, skeletal and musculoskeletal system disease or other diseases, and the investigators judge that this history may affect drug metabolism or safety; Known allergic to Ramucirumab or its excipients; Known history of allergic diseases or allergic constitution; History of hypertension or abnormal blood pressure at screening/baseline measurement (systolic blood pressure (SBP) > 140 mmHg, and/or diastolic blood pressure (DBP) >90 mmHg, confirmed by one repeat measurement on the same day); A history of clinically significant albuminuria (urine routine examination, albuminuria 2+ and above) or albuminuria as assessed by the investigator; Had received treatment of Ramucirumab or VEGFR2 receptor antagonist, or other antibody or protein drugs that target VEGFR2 receptor; Had received any live viral vaccine within 2 months prior to study drug infusion, or required vaccination between the screening period and the end of the study, had used any monoclonal antibody or biologic drug within 12 months prior to study drug administration, or planned to receive any monoclonal antibody or biologic drug within 12 months after study drug administration; had unhealed wound ulcers or fractures, or had undergone major surgery within 3 months prior to study drug infusion or expected to undergo major surgery during the study period or within 2 months after study completion; had taken any prescription drugs, over-the-counter drugs, any vitamin products, or herbs within 14 days prior to use of the study drug; Patients with abnormal examinations and clinical significance during the screening period; Blood donation or significant blood loss within 3 months prior to use of the study drug (>450 mL); Have taken the study drug or participated in any clinical trial of the drug within 3 months prior to the use of the study drug; Smokers who smoked more than 5 cigarettes a day in the 3 months before the test; Test positive for alcohol or have a history of alcohol abuse (14 units of alcohol per week: 1 unit =360 mL of beer or 45 mL of 40% spirits or 150 mL of wine); Test positive for drugs or have a history of drug abuse in the past five years or have used drugs in the three months prior to the test; Hepatitis (including hepatitis B and C), AIDS, syphilis positive screening; Patients with difficulty in venous blood collection or who cannot tolerate venipuncture; Unable or unable to comply with ward management regulations, poor compliance during the study, or unable to follow protocol requirements to complete the study; Subjects unable to complete the experiment due to personal reasons; Conditions considered unsuitable for inclusion by other researchers.

Sites / Locations

  • Affiliated Hospital of Changchun University of Traditional Chinese Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ramucirumab injection

Cyramza

Arm Description

8mg/kg, Single intravenous infusion

8mg/kg, Single intravenous infusion

Outcomes

Primary Outcome Measures

Area under drug concentration - time curve (AUC0-t)
Area under the curve from zero to the lowest detectable blood drug concentration.

Secondary Outcome Measures

Area under drug concentration - time curve (AUC0-∞)
The area under the curve extrapolating from zero to infinity.
Peak concentration (Cmax)
Peak maximum plasma drug concentration
Peak concentration time (Tmax)
Time to reach maximum plasma concentration after dosing
Clearance rate (CL)
Percentage of the organ-scavenging drugs that eliminated by the body
Half-life (T1/2)
The time it takes for serum drug concentrations to drop by half
Apparent volume of distribution (Vd)
Apparent volume of distribution after administration

Full Information

First Posted
March 24, 2023
Last Updated
March 24, 2023
Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05800418
Brief Title
Clinical Study to Compare the Pharmacokinetics and Safety of Ramucirumab Injection With Cyramza ® in Healthy Male Volunteers
Official Title
Phase I Clinical Study of Single-center, Randomized, Double-blind, Single-dose, Parallel Comparison of the Pharmacokinetics and Safety of Ramucirumab Injection and Cyramza® in Healthy Male Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
November 4, 2019 (Actual)
Primary Completion Date
February 18, 2020 (Actual)
Study Completion Date
February 18, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Ramucirumab is a biosimilar drug of CYRAMZA® produced by Chiatai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., LTD. It is a vascular endothelial growth factor receptor 2 (VEGFR-2) antagonist. This single-center, randomized, double-blind, single-dose, parallel phase I study of Ramucirumab injection versus Cyramza ® in healthy male volunteers was designed to evaluate the similarities in pharmacokinetics, tolerance, safety and immunogenicity of Ramucirumab and CYRAMZA®.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer, Non-small Cell Lung Cancer, Colo-rectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
88 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ramucirumab injection
Arm Type
Experimental
Arm Description
8mg/kg, Single intravenous infusion
Arm Title
Cyramza
Arm Type
Active Comparator
Arm Description
8mg/kg, Single intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Ramucirumab Injection
Intervention Description
Ramucirumab injection biosimilar products manufactured by Chia Tai Tianqing Pharmaceutical,
Intervention Type
Drug
Intervention Name(s)
Ramucirumab Injection [Cyramza]
Intervention Description
Ramucirumab Injection is a humanized monoclonal antibody based on the human immunoglobulin G1(IgG1) skeleton sequence, developed by Eli Lilly Co., the bran name is Cyramza. Ramucirumab is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist that specifically binds to VEGF receptor 2 and blocks VEGFR ligand, VEGF-A, VEGF-C, and VEGF-D binding to the receptor. As a result, Ramucirumab inhibits ligand-stimulated VEGF receptor 2 activation, thereby inhibiting ligand-induced proliferation, and human endothelial cell migration. Ramucirumab inhibits angiogenesis, thereby blocking the tumor's blood vessel supply.
Primary Outcome Measure Information:
Title
Area under drug concentration - time curve (AUC0-t)
Description
Area under the curve from zero to the lowest detectable blood drug concentration.
Time Frame
Within 60 minutes before administration to 1680 hours after administration.
Secondary Outcome Measure Information:
Title
Area under drug concentration - time curve (AUC0-∞)
Description
The area under the curve extrapolating from zero to infinity.
Time Frame
Within 60 minutes before administration to 1680 hours after administration.
Title
Peak concentration (Cmax)
Description
Peak maximum plasma drug concentration
Time Frame
Within 60 minutes before administration to 1680 hours after administration.
Title
Peak concentration time (Tmax)
Description
Time to reach maximum plasma concentration after dosing
Time Frame
Within 60 minutes before administration to 1680 hours after administration.
Title
Clearance rate (CL)
Description
Percentage of the organ-scavenging drugs that eliminated by the body
Time Frame
Within 60 minutes before administration to 1680 hours after administration.
Title
Half-life (T1/2)
Description
The time it takes for serum drug concentrations to drop by half
Time Frame
Within 60 minutes before administration to 1680 hours after administration.
Title
Apparent volume of distribution (Vd)
Description
Apparent volume of distribution after administration
Time Frame
Within 60 minutes before administration to 1680 hours after administration.

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Sign informed consent form before the study and fully understand the study content, process and possible adverse reactions; Be able to complete the study according to the requirements of the test plan; Male subjects aged 18-65 years (included); The subject should weigh at least 50kg. Body mass index (BMI) = weight (kg)/ height2(m2), BMI in the range of 19 to 26 (included); Health status: no mental abnormality, no medical history of abnormal cardiovascular system, nervous system, respiratory system, digestive system, urinary system, endocrine system and metabolism; Normal or abnormal vital signs, physical examination, laboratory examination, electrocardiogram and imaging examination with no clinical significance; Have no pregnancy plan and voluntarily take effective contraception measures from 2 weeks before the study drug administration to at least 6 months after the last dose. Exclusion Criteria: Have a history of neuropsychiatric system, respiratory system, cardiovascular system, digestive system, hemolymph system, liver and kidney insufficiency, endocrine system, skeletal and musculoskeletal system disease or other diseases, and the investigators judge that this history may affect drug metabolism or safety; Known allergic to Ramucirumab or its excipients; Known history of allergic diseases or allergic constitution; History of hypertension or abnormal blood pressure at screening/baseline measurement (systolic blood pressure (SBP) > 140 mmHg, and/or diastolic blood pressure (DBP) >90 mmHg, confirmed by one repeat measurement on the same day); A history of clinically significant albuminuria (urine routine examination, albuminuria 2+ and above) or albuminuria as assessed by the investigator; Had received treatment of Ramucirumab or VEGFR2 receptor antagonist, or other antibody or protein drugs that target VEGFR2 receptor; Had received any live viral vaccine within 2 months prior to study drug infusion, or required vaccination between the screening period and the end of the study, had used any monoclonal antibody or biologic drug within 12 months prior to study drug administration, or planned to receive any monoclonal antibody or biologic drug within 12 months after study drug administration; had unhealed wound ulcers or fractures, or had undergone major surgery within 3 months prior to study drug infusion or expected to undergo major surgery during the study period or within 2 months after study completion; had taken any prescription drugs, over-the-counter drugs, any vitamin products, or herbs within 14 days prior to use of the study drug; Patients with abnormal examinations and clinical significance during the screening period; Blood donation or significant blood loss within 3 months prior to use of the study drug (>450 mL); Have taken the study drug or participated in any clinical trial of the drug within 3 months prior to the use of the study drug; Smokers who smoked more than 5 cigarettes a day in the 3 months before the test; Test positive for alcohol or have a history of alcohol abuse (14 units of alcohol per week: 1 unit =360 mL of beer or 45 mL of 40% spirits or 150 mL of wine); Test positive for drugs or have a history of drug abuse in the past five years or have used drugs in the three months prior to the test; Hepatitis (including hepatitis B and C), AIDS, syphilis positive screening; Patients with difficulty in venous blood collection or who cannot tolerate venipuncture; Unable or unable to comply with ward management regulations, poor compliance during the study, or unable to follow protocol requirements to complete the study; Subjects unable to complete the experiment due to personal reasons; Conditions considered unsuitable for inclusion by other researchers.
Facility Information:
Facility Name
Affiliated Hospital of Changchun University of Traditional Chinese Medicine
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China

12. IPD Sharing Statement

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Clinical Study to Compare the Pharmacokinetics and Safety of Ramucirumab Injection With Cyramza ® in Healthy Male Volunteers

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