Clinical trial NCT03777488: Pharmacokinetics of Tranexamic Acid After Oral, Intramuscular or Intravenous Administration: a Prospective, Randomised, Cross-over Trial in Healthy Volunteers.
Official title: Pharmacokinetics of Tranexamic Acid After Oral, Intramuscular or Intravenous Administration: a Prospective, Randomised, Cross-over Trial in Healthy Volunteers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer Study
Keywords: pharmacokinetics, tranexamic acid
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
First posted: 2018-12-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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: 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

Eligibility criteria: 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)

Primary outcomes:
measure: Serum tranexamic acid concentrations versus time profiles for each route of administration (Oral, intramuscular and intravenous)
timeFrame: 24 hours
Secondary outcomes:
measure: Pain during after administration (visual analogue scale) for each administration route
timeFrame: 8 hours
measure: Reaction at site of injection for intramuscular and Iintravenous routes
timeFrame: 24 hours
measure: • Correlation between serum and dry blood spot concentrations for each administration route
timeFrame: 24 hours
Other outcomes:
Locations:
city: Montigny-Le-Bretonneux
country: France
facility: UFR Sciences de la Santé Simone Veil Université Versailles Saint Quentin en Yvelines
city: Paris
country: France
facility: Unité de Recherche Clinique Paris Descartes Necker Cochin, Hôpital Necker-Enfants Malades
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Haleema Shakur-Still
role: STUDY_CHAIR
affiliation: London School of Hygiene and Tropical Medicine
name: Ian Roberts
role: STUDY_CHAIR
References:
citation: Grassin-Delyle S, Semeraro M, Lamy E, Urien S, Runge I, Foissac F, Bouazza N, Treluyer JM, Arribas M, Roberts I, Shakur-Still H. Pharmacokinetics of tranexamic acid after intravenous, intramuscular, and oral routes: a prospective, randomised, crossover trial in healthy volunteers. Br J Anaesth. 2022 Mar;128(3):465-472. doi: 10.1016/j.bja.2021.10.054. Epub 2022 Jan 5.