First‐in‐Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of an Oral Formulation of DS‐1040, an Inhibitor of the Activated Form of Thrombin‐Activatable Fibrinolysis Inhibitor, in Healthy Subjects

2019 ◽  
Vol 59 (12) ◽  
pp. 1669-1677
Author(s):  
Jin Zhou ◽  
Tharin Limsakun ◽  
Ophelia Yin ◽  
Vance Warren ◽  
Cynthia Zamora ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Human Study ◽  
Oral Formulation ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Fibrinolysis Inhibitor

A first-in-human study of DS-1040, an inhibitor of the activated form of thrombin-activatable fibrinolysis inhibitor, in healthy subjects

2017 ◽  
Vol 15 (5) ◽  
pp. 961-971 ◽  
Author(s):  
J. Zhou ◽  
J. Kochan ◽  
O. Yin ◽  
V. Warren ◽  
C. Zamora ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Human Study ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Fibrinolysis Inhibitor

scholarly journals First-in-human study to assess the safety, pharmacokinetics and pharmacodynamics of BMS-962212, a direct, reversible, small molecule factor XIa inhibitor in non-Japanese and Japanese healthy subjects

2018 ◽  
Vol 84 (5) ◽  
pp. 876-887 ◽  
Author(s):  
Vidya Perera ◽  
Joseph M. Luettgen ◽  
Zhaoqing Wang ◽  
Charles E. Frost ◽  
Cynthia Yones ◽  
...  
Keyword(s):  
Small Molecule ◽  
Healthy Subjects ◽  
Human Study ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Factor Xia

Plasma TAFI Antigen Variations in Healthy Subjects

2000 ◽  
Vol 83 (06) ◽  
pp. 902-905 ◽  
Author(s):  
P. Chetaille ◽  
M. C. Alessi ◽  
D. Kouassi ◽  
P. E. Morange ◽  
I. Juhan-Vague
Keyword(s):  
Healthy Subjects ◽  
Healthy Individuals ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Mean Values ◽  
Black African ◽  
Individual Variations ◽  
Caucasian Men ◽  
Fibrinolysis Inhibitor ◽  
The One ◽  
Physiological Variations

SummaryThe Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a recently described inhibitor of fibrinolysis. The physiological variations of plasma TAFI antigen are not well known. We studied TAFI antigen values in healthy populations with a commercially available kit from Milan Analytica (Switzerland). Broad range of TAFI antigen values (from 41% to 259%) was found in a population of 249 healthy individuals. Gender as well as pregnancy did not influence mean values of TAFI antigen. There was a positive correlation between TAFI antigen and age in female (r = 0.28; p <0.05) but not in male populations. Mean TAFI antigen value of a black African male group [mean ± SD (range): 87 ± 23 (39-144%)] was significantly lower than the one of age matched Caucasian men [114 ± 34 (52-259%)] (p <0.0001). TAFI antigen values were very stable within individuals, they did not significantly vary on day time or at several months period.Thus, in contrast to large inter-individual variations, TAFI antigen levels are quite stable within individuals.

Favourable safety profile of S62798, a potent TAFIa (activated thrombin-activatable fibrinolysis inhibitor) inhibitor, in first-in-man study in healthy subjects

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Petit Dop ◽  
M Latreille ◽  
L Guicherd ◽  
J.C Mertens ◽  
K Claesen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Healthy Subjects ◽  
Clot Lysis ◽  
Funding Source ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Lysis Time ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Fibrinolysis Inhibitor ◽  
Clot Lysis Time

Abstract Background Thromboembolic diseases, such as venous thromboembolic diseases represent a significant public health burden. S62798, a selective and potent inhibitor of activated thrombin-activatable fibrinolysis inhibitor (TAFIa), is being developed as a fibrinolysis enhancer for the treatment of thromboembolic diseases, including pulmonary embolism. TAFIa inhibits the fibrinolysis by limiting plasmin generation. Objectives This double-blind, randomised, placebo-controlled first-in-man study was conducted to investigate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of S62798 in healthy subjects. Methods Young male (18–40 years) subjects were randomised 3:1 to single ascending doses of S62798 ranging from 3.2 mg to 320 mg or placebo, administered as an intravenous bolus followed by a 7 hour 2-step infusion (part 1), or to 30 mg or 40 mg or placebo administered as a 1-min bolus (part 2). Follow-up ranged from 6 to 13 days post S62798 administration depending on cohorts. Exclusion criteria included bleeding disorders, recent bleeding, and abnormal blood coagulation parameters. Anticoagulant/antiplatelet treatments were not allowed for 30 days prior to and during the study. Safety was assessed by recording adverse events (AE), physical examination, vital signs, biochemical, haematological and haemostasis parameters (prothrombin time, activated partial thromboplastin time, thrombin clotting time, D-Dimers and fibrinogen). Plasma and urine samples for PK assessment were collected pre-dose and up to day 13 to assess the full PK profile. In part 1, ex vivo TAFIa inhibition (spiking of purified human TAFIa) and in vitro clot lysis time were assessed at pre-dose, during and after infusion. The study was performed in France in accordance with the declaration of Helsinki revised in Fortaleza. EudraCT number: 2016–002108–25. Results A total of 56 subjects were randomized to part 1 and 16 to part 2. Subjects were (mean ± SD) 29.5 ±- 5.7 years old with a BMI of 23.9±2.6 kg/m2 in part 1 and 31.4±5.2 years old with a BMI of 23.9±2.5 kg/m2 in part 2. All doses of S62798 administered as a bolus and infusion or a single bolus were well tolerated, and no serious adverse events or discontinuations resulting from AEs occurred during the study. No effects of S62798 on haemostasis parameters were observed. Cardiac safety assessed by 12-lead 24h Holter ECG showed no relevant abnormalities. Plasma exposure of S62798 increased proportionally with the dose. S62798 inhibits TAFIa activity and decreases clot lysis time (reflecting TAFIa activity inhibition) rapidly and dose-dependently in all treated groups. Conclusions S62798, a potent TAFIa inhibitor, has a favourable safety profile with a linear PK. PD results on TAFIa inhibition and clot lysis assay suggest that S62798 has relevant properties to pursue clinical development as an enhancer of endogenous fibrinolysis for the treatment of thromboembolic diseases Funding Acknowledgement Type of funding source: Private company. Main funding source(s): IRIS

scholarly journals P135 A phase I, first-in-human study to assess the safety, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of M5049, a dual antagonist of TLR7/8, in healthy subjects

2020 ◽  
Author(s):  
Andreas Port ◽  
Lena Klopp-Schulze ◽  
Jamie Shaw ◽  
Elizabeth Hussey ◽  
Nadra Mammasse ◽  
...  
Keyword(s):  
Phase I ◽  
Healthy Subjects ◽  
Human Study ◽  
Pharmacokinetics And Pharmacodynamics
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