Anfibatide Phase 1 Clinical Trial in Healthy Volunteers

First Assessment of the Glycoprotein Ib-IV-V Complex Antagonist Anfibatide in Healthy Human Volunteers

In this 94 healthy subjects Phase I clinical trial, we assess the clinical profile of Anfibatide, a specific glycoprotein Ib antagonist. This study represents the first clinical evidence that Anfibatide exhibits strong anti-platelet effects, excellent reversibility, and low bleeding potential in healthy human subjects.

Study Overview

• Status: Completed
• Conditions: Coronary Heart Disease; Coagulation Disorder
• Intervention / Treatment: Drug: Anfibatide

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 28 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1) Healthy volunteers, aged 18-28 years, male and female were included, age difference less than 10 years;
• 2) Body weight: with body mass index (BMI) between 19-24, difference less than 10kg in the same group, BMI=body weight(kg)/height2;
• 3) Past medical history: no history of heart, liver, kidney, digestive tract, nervous system and metabolic disorder, or ulcer, significant hemorrhage, without the history of drug allergy and postural hypotension;
• 4) Medical examinations: with normal results in overall examinations (including heart rate, blood pressure, auscultation of heart and lung, palpation of liver and spleen, hepatic and renal function, hematology, coagulation function, urine analysis, stool analysis and occult blood test, electrocardiogram);
• 5) Have not received any medications within 2 weeks before the study;
• 6) Willing to participate in the study and give a signed informed consent form after understanding the study procedures and potential adverse reactions of the study product.

Exclusion Criteria:

• 1) History of HBV or HCV infection;
• 2) Addicted to smoking or alcohol;
• 3) Women during pregnancy, lactation or menstrual period;
• 4) Past history of hemoptysis, bloody stool, bleeding spots in the skin and mucous membrane, or hemorrhagic tendency (find themselves prone to bleeding in gums, nose, skin and mucous membrane, or hemoptysis);
• 5) History of active bleeding (such as peptic ulcer, hemorrhoids, active tuberculosis, subacute bacterial endocarditis, etc);
• 6) Blood platelet count less than 150×109;
• 7) Trauma history (e.g., craniocerebral trauma) recently;
• 8) Past history of unexplained syncope or convulsion;
• 9) History of organic or psychogenic disease or the disabled;
• 10) Persons who were unlikely to participate in the study (such as the infirm) in the investigator's opinion;
• 11) Have donated blood or experienced blood collection in other trials within 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose gourp 1; Anfibatide injection at the concentration of 0.33μg/60kg in healthy volunteers	Drug: Anfibatide; To investigate the safety and tolerability of single intravenous dose of Antiplatelet Thrombolysin for Injection of 0.33,0.66,1.0,1.5,2.0,3.0,4.0,5.0μg (body weight 60kg) in healthy volunteers.; To investigate the safety and tolerability of continuous administration of three dose regimen: ① give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours. ② give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours. ③ give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.
Experimental: Single dose group 2; Anfibatide injection at the concentration of 0.66μg/60kg in healthy volunteers	Drug: Anfibatide; To investigate the safety and tolerability of single intravenous dose of Antiplatelet Thrombolysin for Injection of 0.33,0.66,1.0,1.5,2.0,3.0,4.0,5.0μg (body weight 60kg) in healthy volunteers.; To investigate the safety and tolerability of continuous administration of three dose regimen: ① give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours. ② give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours. ③ give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.
Experimental: Single dose groups 3; Anfibatide injection at the concentration of1.0μg/60kg in healthy volunteers	Drug: Anfibatide; To investigate the safety and tolerability of single intravenous dose of Antiplatelet Thrombolysin for Injection of 0.33,0.66,1.0,1.5,2.0,3.0,4.0,5.0μg (body weight 60kg) in healthy volunteers.; To investigate the safety and tolerability of continuous administration of three dose regimen: ① give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours. ② give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours. ③ give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.
Experimental: Single dose group 4; Anfibatide injection at the concentration of 1.5μg/60kg in healthy volunteers	Drug: Anfibatide; To investigate the safety and tolerability of single intravenous dose of Antiplatelet Thrombolysin for Injection of 0.33,0.66,1.0,1.5,2.0,3.0,4.0,5.0μg (body weight 60kg) in healthy volunteers.; To investigate the safety and tolerability of continuous administration of three dose regimen: ① give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours. ② give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours. ③ give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.
Experimental: Single dose group 5; Anfibatide injection at the concentration of 2.0μg/60kg in healthy volunteers	Drug: Anfibatide; To investigate the safety and tolerability of single intravenous dose of Antiplatelet Thrombolysin for Injection of 0.33,0.66,1.0,1.5,2.0,3.0,4.0,5.0μg (body weight 60kg) in healthy volunteers.; To investigate the safety and tolerability of continuous administration of three dose regimen: ① give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours. ② give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours. ③ give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.
Experimental: Single dose group 6; Anfibatide injection at the concentration of 3.0μg/60kg in healthy volunteers	Drug: Anfibatide; To investigate the safety and tolerability of single intravenous dose of Antiplatelet Thrombolysin for Injection of 0.33,0.66,1.0,1.5,2.0,3.0,4.0,5.0μg (body weight 60kg) in healthy volunteers.; To investigate the safety and tolerability of continuous administration of three dose regimen: ① give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours. ② give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours. ③ give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.
Experimental: Single dose group 7; Anfibatide injection at the concentration of 4.0μg/60kg in healthy volunteers	Drug: Anfibatide; To investigate the safety and tolerability of single intravenous dose of Antiplatelet Thrombolysin for Injection of 0.33,0.66,1.0,1.5,2.0,3.0,4.0,5.0μg (body weight 60kg) in healthy volunteers.; To investigate the safety and tolerability of continuous administration of three dose regimen: ① give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours. ② give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours. ③ give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.
Experimental: Single dose group 8; Anfibatide injection at the concentration of 5.0μg/60kg in healthy volunteers	Drug: Anfibatide; To investigate the safety and tolerability of single intravenous dose of Antiplatelet Thrombolysin for Injection of 0.33,0.66,1.0,1.5,2.0,3.0,4.0,5.0μg (body weight 60kg) in healthy volunteers.; To investigate the safety and tolerability of continuous administration of three dose regimen: ① give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours. ② give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours. ③ give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.
Experimental: Multiple dose group 9; Give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours	Drug: Anfibatide; To investigate the safety and tolerability of single intravenous dose of Antiplatelet Thrombolysin for Injection of 0.33,0.66,1.0,1.5,2.0,3.0,4.0,5.0μg (body weight 60kg) in healthy volunteers.; To investigate the safety and tolerability of continuous administration of three dose regimen: ① give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours. ② give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours. ③ give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.
Experimental: Multiple dose group 10; Give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.	Drug: Anfibatide; To investigate the safety and tolerability of single intravenous dose of Antiplatelet Thrombolysin for Injection of 0.33,0.66,1.0,1.5,2.0,3.0,4.0,5.0μg (body weight 60kg) in healthy volunteers.; To investigate the safety and tolerability of continuous administration of three dose regimen: ① give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours. ② give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours. ③ give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.
Experimental: Multiple dose group 11; Give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours	Drug: Anfibatide; To investigate the safety and tolerability of single intravenous dose of Antiplatelet Thrombolysin for Injection of 0.33,0.66,1.0,1.5,2.0,3.0,4.0,5.0μg (body weight 60kg) in healthy volunteers.; To investigate the safety and tolerability of continuous administration of three dose regimen: ① give intravenous injection of 3μg as the first dose and after 1.5 hours, infusion of the study product 0.12μg/h for 24 hours. ② give intravenous injection of 3μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours. ③ give intravenous injection of 5μg as the first dose and immediately infusion of the study product 0.12μg/h for 24 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoints	To investigate the number of adverse events in patients with single or multiple intravenous injection/infusion of Antiplatelet	24 Hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under Curve (AUC)	To observe area under curve characteristics of Anfibatide in single or multiple dose groups	Predose, 0,1,2,3,4,6,8,12,24,48,72,96 Hours

Collaborators and Investigators

• Sponsor: Lee's Pharmaceutical Limited

Publications and helpful links

General Publications

• Li BX, Dai X, Xu XR, Adili R, Neves MAD, Lei X, Shen C, Zhu G, Wang Y, Zhou H, Hou Y, Ni T, Pasman Y, Yang Z, Qian F, Zhao Y, Gao Y, Liu J, Teng M, Marshall AH, Cerenzia EG, Li ML, Ni H. In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIbalpha. Sci Rep. 2021 Jun 3;11(1):11663. doi: 10.1038/s41598-021-91165-8.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: April 25, 2012
• First Submitted That Met QC Criteria: April 26, 2012
• First Posted (Estimate): April 30, 2012

Study Record Updates

• Last Update Posted (Estimate): April 30, 2012
• Last Update Submitted That Met QC Criteria: April 26, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Hematologic Diseases; Hemorrhagic Disorders; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Hemostatic Disorders; Blood Coagulation Disorders
• Other Study ID Numbers: LeesPharm_Anfibatide_Phase1