Pharmacodynamic Study - Phase I Experimental Drug: Porcine sodium heparin, injectable solution - 5,000 IU/mL; Blau Farmacêutica S/A. Comparator Drug: Heparin Sodium Injection, USP, injectable solution - 5,000 IU/mL; Fresenius Kabi Lake Zurich. Evaluate the equivalence in terms of pharmacodynamics of heparin sodium (test product) and Heparin Sodium Injection, USP (comparator product). The clinical trial will last approximately 08 weeks and the study population will consist of 68 healthy research participants, 34 women and 34 men.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
68
intravenous Heparin
Evaluation of Amax parameter pharmacodynamics for the anti-FXA marker
Amax: Maximum response, understood as the highest concentration, detected in plasma after treatment. The conclusion by the average equivalence is achieved when the confidence intervals 90% of the ratio of geometric averages of experimental and comparator drugs are between 80% and 125%.
Time frame: 12 hours of blood collection from the administration of the test drug and 12 hours of blood collection from the administration of the reference drug. The doses will be separated by a minimum interval of 14 days.
Evaluation of ASCE0-t parameter pharmacodynamics for the anti-FXA marker
ASCE0-T: area under the effect-based effect curve versus time from zero to the last experimentally determined concentration; The conclusion by the average equivalence is achieved when the confidence intervals 90% of the ratio of geometric averages of experimental and comparator drugs are between 80% and 125%
Time frame: 12 hours of blood collection from the administration of the test drug and 12 hours of blood collection from the administration of the reference drug. The doses will be separated by a minimum interval of 14 days.
Evaluation of ASCE0-inf parameter pharmacodynamics for the anti-FXA marker
ASCE0-inf: Area under the effect curve based on concentration versus time from zero to infinity experimentally determined. The conclusion by the average equivalence is achieved when the confidence intervals 90% of the ratio of geometric averages of experimental and comparator drugs are between 80% and 125%.
Time frame: 12 hours of blood collection from the administration of the test drug and 12 hours of blood collection from the administration of the reference drug. The doses will be separated by a minimum interval of 14 days.
Evaluation of Amax parameter pharmacodynamics for the anti-FIIA marker
Amax: Maximum response, understood as the highest concentration, detected in plasma after treatment. The conclusion by the average equivalence is achieved when the confidence intervals 90% of the ratio of geometric averages of experimental and comparator drugs are between 80% and 125%.
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Time frame: 12 hours of blood collection from the administration of the test drug and 12 hours of blood collection from the administration of the reference drug. The doses will be separated by a minimum interval of 14 days.
Evaluation of ASCE0-t parameter pharmacodynamics for the anti-FIIA marker
ASCE0-T: area under the effect-based effect curve versus time from zero to the last experimentally determined concentration; The conclusion by the average equivalence is achieved when the confidence intervals 90% of the ratio of geometric averages of experimental and comparator drugs are between 80% and 125%.
Time frame: 12 hours of blood collection from the administration of the test drug and 12 hours of blood collection from the administration of the reference drug. The doses will be separated by a minimum interval of 14 days.
Sequence effects of pharmacodynamic parameters for the Anti-FXa marker - Analysis of variance (ANOVA)
Amax and ASCEo-t and ASCEo-inf parameters will be analyzed by analyzing ANOVA variance to evaluate the sequence effects of the anti-fii marker
Time frame: 12 hours of blood collection from the administration of the test drug and 12 hours of blood collection from the administration of the reference drug. The doses will be separated by a minimum interval of 14 days.
Sequence effects of pharmacodynamic parameters for the Anti-FIIa marker - Analysis of variance (ANOVA)
Amax and ASCEo-t parameters will be analyzed by analyzing ANOVA variance to evaluate the sequence effects of the anti-fii marker
Time frame: 12 hours of blood collection from the administration of the test drug and 12 hours of blood collection from the administration of the reference drug. The doses will be separated by a minimum interval of 14 days.
Ratio of Anti-FXa/Anti-FIIa activity based on the pharmacodynamic parameter ASCE0-t
The ratio for anti-FXa/anti-FIIa activity of the ASCE0-t parameter will be evaluated. , the evaluation will be performed by comparing the interval of 90% of the ratio with the equivalence criterion 80% - 125%.
Time frame: 12 hours of blood collection from the administration of the test drug and 12 hours of blood collection from the administration of the reference drug. The doses will be separated by a minimum interval of 14 days.
Occurrence of adverse events and serious eventsevents
Adverse events will be monitored for two months and reported in the final report. * Total of adverse events; * Total number of research participants who had adverse events; * Number of adverse events per period; * Number of adverse events due to causality; * Number of adverse events by type of medicine (formulation); * Number of adverse EA intensity events.
Time frame: 2 months
Evaluation of Amax parameter pharmacodynamics for the tissue factor pathway inhibitor (TFPI) activity
TFPI serum concentrations will be quantified by ELISA method. will be evaluated by comparing the 90% interval for the ratios with the acceptance criteria 80% - 125%.
Time frame: 12 hours of blood collection from the administration of the test drug and 12 hours of blood collection from the administration of the reference drug. The doses will be separated by a minimum interval of 14 days.
Evaluation of ASCEo-t parameter pharmacodynamics for the tissue factor pathway inhibitor (TFPI) activity
TFPI serum concentrations will be quantified by ELISA method. will be evaluated by comparing the 90% interval for the ratios with the acceptance criteria 80% - 125%.
Time frame: 12 hours of blood collection from the administration of the test drug and 12 hours of blood collection from the administration of the reference drug. The doses will be separated by a minimum interval of 14 days.
Evaluation of ASCEo-inf parameter pharmacodynamics for the tissue factor pathway inhibitor (TFPI) activity
TFPI serum concentrations will be quantified by ELISA method. will be evaluated by comparing the 90% interval for the ratios with the acceptance criteria 80% - 125%.
Time frame: 12 hours of blood collection from the administration of the test drug and 12 hours of blood collection from the administration of the reference drug. The doses will be separated by a minimum interval of 14 days.