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

London School of Hygiene and Tropical Medicine

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteer Study

Treatments: Drug: Tranexamic acid 1 gram intramuscular; Drug: Tranexamic acid 2 grams oral solution; Drug: Tranexamic Acid 1 gram intravenously

Study type: Interventional

Funder types: Other

Identifiers

NCT03777488

2018/KEP/205

Details and patient eligibility

About

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.

Full description

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

Enrollment: 15 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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15 participants in 6 patient groups

Tranexamic acid Group 1

Experimental group

Description:

Participants will receive tranexamic acid in the following order: First Dose: Intravenous Second Dose: Intramuscular Third Dose: Oral

Treatment:

Drug: Tranexamic Acid 1 gram intravenously

Drug: Tranexamic acid 2 grams oral solution

Drug: Tranexamic acid 1 gram intramuscular

Tranexamic acid Group 2

Experimental group

Description:

Participants will receive tranexamic acid in the following order: First Dose: Intravenous Second Dose: Oral Third Dose: Intramuscular

Treatment:

Drug: Tranexamic Acid 1 gram intravenously

Drug: Tranexamic acid 2 grams oral solution

Drug: Tranexamic acid 1 gram intramuscular

Tranexamic acid Group 3

Experimental group

Description:

Participants will receive tranexamic acid in the following order: First Dose: Intramuscular Second Dose: Intravenous Third Dose: Oral

Treatment:

Drug: Tranexamic Acid 1 gram intravenously

Drug: Tranexamic acid 2 grams oral solution

Drug: Tranexamic acid 1 gram intramuscular

Tranexamic acid Group 4

Experimental group

Description:

Participants will receive tranexamic acid in the following order: First Dose: Intramuscular Second Dose: Oral Third Dose: Intravenous

Treatment:

Drug: Tranexamic Acid 1 gram intravenously

Drug: Tranexamic acid 2 grams oral solution

Drug: Tranexamic acid 1 gram intramuscular

Tranexamic acid Group 5

Experimental group

Description:

Participants will receive tranexamic acid in the following order: First Dose: Oral Second Dose: Intravenous Third Dose: Intramuscular

Treatment:

Drug: Tranexamic Acid 1 gram intravenously

Drug: Tranexamic acid 2 grams oral solution

Drug: Tranexamic acid 1 gram intramuscular

Tranexamic acid Group 6

Experimental group

Description:

Participants will receive tranexamic acid in the following order: First Dose: Oral Second Dose: Intramuscular Third Dose: Intravenous

Treatment:

Drug: Tranexamic Acid 1 gram intravenously

Drug: Tranexamic acid 2 grams oral solution

Drug: Tranexamic acid 1 gram intramuscular