Pharmacokinetics of Tranexamic Acid After Oral, Intramuscular or Intravenous Administration: a Prospective, Randomised, Cross-over Trial in Healthy Volunteers.

Study Overview
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Brief Summary
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This is a Phase 1 study which aims to determine the pharmacokinetics and local and systemic tolerance of tranexamic acid in healthy volunteers using a population approach after oral, intramuscular or intravenous administration. It will also determine the feasibility of measuring tranexamic acid in spots of dry capillary blood.

Detailed Description
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Fifteen healthy volunteers will receive in random order 1 gram of intravenous and intramuscular injections and 2 grams of oral tranexamic acid solution. Blood samples will be taken at: T0+ 5min (only for IV route) T0+30min T0+1h T0+2h T0+3h T0+4h T0+5h T0+6h T0+8h (only for IM and PO routes) T0+24h

Official Title
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Pharmacokinetics of Tranexamic Acid After Oral, Intramuscular or Intravenous Administration: a Prospective, Randomised, Cross-over Trial in Healthy Volunteers.

Conditions
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Healthy Volunteer Study

Intervention / Treatment
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* Drug: Tranexamic Acid 1 gram intravenously
* Drug: Tranexamic acid 2 grams oral solution
* Drug: Tranexamic acid 1 gram intramuscular


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult healthy volunteers both men and non-pregnant women ≥18-≤45-year-old Body mass index between ≥18 and ≤30 kg/m2, and bodyweight between ≥50 and ≤100 kg Coagulation test results of fibrinogen, D-dimers, prothrombin time and a partial thromboplastin time within normal limits at screening Normal renal function based on medical history and laboratory tests If a woman, must have a negative urine β-human chorionic gonadotropin (βhCG) pregnancy test at screening and inclusion visits Provision of signed informed consent prior to any study specific procedure People with public healthcare insurance (in France) Exclusion Criteria: Previous thrombotic event or pre-existing pro-thrombotic disease Any history of seizures Any chronic or active cardiovascular or renal disease Planned general anaesthesia or surgery in the 3 months following inclusion Pregnant and/or breastfeeding Known allergy to the study drugs or any of the excipients of the formulations Use of any prescription or non-prescription medication (other than hormonal contraception) within 7 days before the first dose of the study drug is scheduled Inability to give informed consent Previous participation during the year in clinical studies compensated for an amount incompatible with participation in this study, verified by recording in the national register of subjects participating in human research trials Legal criteria: People deprived of liberty by judicial or administrative decision Adult protected by law (France)

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic acid Group 1<br>Participants will receive tranexamic acid in the following order: First Dose: Intravenous Second Dose: Intramuscular Third Dose: Oral | Drug: Tranexamic Acid 1 gram intravenously<br>* Intravenous tranexamic acid crossover to oral and intramuscular arms<br>Drug: Tranexamic acid 2 grams oral solution<br>* Oral tranexamic acid crossover to intravenous and intramuscular arms<br>Drug: Tranexamic acid 1 gram intramuscular<br>* Intramuscular tranexamic acid crossover to oral and intravenous arms<br>|
| Experimental: Tranexamic acid Group 2<br>Participants will receive tranexamic acid in the following order: First Dose: Intravenous Second Dose: Oral Third Dose: Intramuscular | Drug: Tranexamic Acid 1 gram intravenously<br>* Intravenous tranexamic acid crossover to oral and intramuscular arms<br>Drug: Tranexamic acid 2 grams oral solution<br>* Oral tranexamic acid crossover to intravenous and intramuscular arms<br>Drug: Tranexamic acid 1 gram intramuscular<br>* Intramuscular tranexamic acid crossover to oral and intravenous arms<br>|
| Experimental: Tranexamic acid Group 3<br>Participants will receive tranexamic acid in the following order: First Dose: Intramuscular Second Dose: Intravenous Third Dose: Oral | Drug: Tranexamic Acid 1 gram intravenously<br>* Intravenous tranexamic acid crossover to oral and intramuscular arms<br>Drug: Tranexamic acid 2 grams oral solution<br>* Oral tranexamic acid crossover to intravenous and intramuscular arms<br>Drug: Tranexamic acid 1 gram intramuscular<br>* Intramuscular tranexamic acid crossover to oral and intravenous arms<br>|
| Experimental: Tranexamic acid Group 4<br>Participants will receive tranexamic acid in the following order: First Dose: Intramuscular Second Dose: Oral Third Dose: Intravenous | Drug: Tranexamic Acid 1 gram intravenously<br>* Intravenous tranexamic acid crossover to oral and intramuscular arms<br>Drug: Tranexamic acid 2 grams oral solution<br>* Oral tranexamic acid crossover to intravenous and intramuscular arms<br>Drug: Tranexamic acid 1 gram intramuscular<br>* Intramuscular tranexamic acid crossover to oral and intravenous arms<br>|
| Experimental: Tranexamic acid Group 5<br>Participants will receive tranexamic acid in the following order: First Dose: Oral Second Dose: Intravenous Third Dose: Intramuscular | Drug: Tranexamic Acid 1 gram intravenously<br>* Intravenous tranexamic acid crossover to oral and intramuscular arms<br>Drug: Tranexamic acid 2 grams oral solution<br>* Oral tranexamic acid crossover to intravenous and intramuscular arms<br>Drug: Tranexamic acid 1 gram intramuscular<br>* Intramuscular tranexamic acid crossover to oral and intravenous arms<br>|
| Experimental: Tranexamic acid Group 6<br>Participants will receive tranexamic acid in the following order: First Dose: Oral Second Dose: Intramuscular Third Dose: Intravenous | Drug: Tranexamic Acid 1 gram intravenously<br>* Intravenous tranexamic acid crossover to oral and intramuscular arms<br>Drug: Tranexamic acid 2 grams oral solution<br>* Oral tranexamic acid crossover to intravenous and intramuscular arms<br>Drug: Tranexamic acid 1 gram intramuscular<br>* Intramuscular tranexamic acid crossover to oral and intravenous arms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum tranexamic acid concentrations versus time profiles for each route of administration (Oral, intramuscular and intravenous) |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain during after administration (visual analogue scale) for each administration route | (Scale 0 - 9) where 0 = no pain and 9 most severe pain | 8 hours | 
| Reaction at site of injection for intramuscular and Iintravenous routes |  | 24 hours | 
| • Correlation between serum and dry blood spot concentrations for each administration route |  | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, tranexamic acid