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

Phase 1

Completed

• Conditions: Healthy Volunteer Study
• Interventions: Drug: Tranexamic Acid 1 gram intravenously; Drug: Tranexamic acid 2 grams oral solution; Drug: Tranexamic acid 1 gram intramuscular

• Registration Number: NCT03777488
• Lead Sponsor: London School of Hygiene and Tropical Medicine

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

Study Timeline

• Study First Submitted: 2018-12-13
• Study First Submitted QC: 2018-12-13
• Study First Posted: 2018-12-17
• Study Start: 2019-10-30
• Status Verified: 2020-02
• Primary Completion: 2020-10-14
• Study Completion: 2020-10-14
• Last Update Submitted: 2020-11-17
• Last Update Posted: 2020-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Tranexamic acid Group 4	Tranexamic acid 1 gram intramuscular	Participants will receive tranexamic acid in the following order: First Dose: Intramuscular Second Dose: Oral Third Dose: Intravenous
Tranexamic acid Group 3	Tranexamic acid 2 grams oral solution	Participants will receive tranexamic acid in the following order: First Dose: Intramuscular Second Dose: Intravenous Third Dose: Oral
Tranexamic acid Group 3	Tranexamic acid 1 gram intramuscular	Participants will receive tranexamic acid in the following order: First Dose: Intramuscular Second Dose: Intravenous Third Dose: Oral
Tranexamic acid Group 5	Tranexamic Acid 1 gram intravenously	Participants will receive tranexamic acid in the following order: First Dose: Oral Second Dose: Intravenous Third Dose: Intramuscular
Tranexamic acid Group 1	Tranexamic Acid 1 gram intravenously	Participants will receive tranexamic acid in the following order: First Dose: Intravenous Second Dose: Intramuscular Third Dose: Oral
Tranexamic acid Group 1	Tranexamic acid 2 grams oral solution	Participants will receive tranexamic acid in the following order: First Dose: Intravenous Second Dose: Intramuscular Third Dose: Oral
Tranexamic acid Group 2	Tranexamic acid 1 gram intramuscular	Participants will receive tranexamic acid in the following order: First Dose: Intravenous Second Dose: Oral Third Dose: Intramuscular
Tranexamic acid Group 4	Tranexamic acid 2 grams oral solution	Participants will receive tranexamic acid in the following order: First Dose: Intramuscular Second Dose: Oral Third Dose: Intravenous
Tranexamic acid Group 6	Tranexamic Acid 1 gram intravenously	Participants will receive tranexamic acid in the following order: First Dose: Oral Second Dose: Intramuscular Third Dose: Intravenous
Tranexamic acid Group 1	Tranexamic acid 1 gram intramuscular	Participants will receive tranexamic acid in the following order: First Dose: Intravenous Second Dose: Intramuscular Third Dose: Oral
Tranexamic acid Group 2	Tranexamic Acid 1 gram intravenously	Participants will receive tranexamic acid in the following order: First Dose: Intravenous Second Dose: Oral Third Dose: Intramuscular
Tranexamic acid Group 2	Tranexamic acid 2 grams oral solution	Participants will receive tranexamic acid in the following order: First Dose: Intravenous Second Dose: Oral Third Dose: Intramuscular
Tranexamic acid Group 3	Tranexamic Acid 1 gram intravenously	Participants will receive tranexamic acid in the following order: First Dose: Intramuscular Second Dose: Intravenous Third Dose: Oral
Tranexamic acid Group 4	Tranexamic Acid 1 gram intravenously	Participants will receive tranexamic acid in the following order: First Dose: Intramuscular Second Dose: Oral Third Dose: Intravenous
Tranexamic acid Group 6	Tranexamic acid 2 grams oral solution	Participants will receive tranexamic acid in the following order: First Dose: Oral Second Dose: Intramuscular Third Dose: Intravenous
Tranexamic acid Group 6	Tranexamic acid 1 gram intramuscular	Participants will receive tranexamic acid in the following order: First Dose: Oral Second Dose: Intramuscular Third Dose: Intravenous
Tranexamic acid Group 5	Tranexamic acid 2 grams oral solution	Participants will receive tranexamic acid in the following order: First Dose: Oral Second Dose: Intravenous Third Dose: Intramuscular
Tranexamic acid Group 5	Tranexamic acid 1 gram intramuscular	Participants will receive tranexamic acid in the following order: First Dose: Oral Second Dose: Intravenous Third Dose: Intramuscular

Primary Outcome Measures

Name	Time	Method
Serum tranexamic acid concentrations versus time profiles for each route of administration (Oral, intramuscular and intravenous)	24 hours

Secondary Outcome Measures

Name	Time	Method
Pain during after administration (visual analogue scale) for each administration route	8 hours	(Scale 0 - 9) where 0 = no pain and 9 most severe pain
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

Trial Locations

Locations (2)

Unité de Recherche Clinique Paris Descartes Necker Cochin, Hôpital Necker-Enfants Malades; 🇫🇷 Paris, France

UFR Sciences de la Santé Simone Veil Université Versailles Saint Quentin en Yvelines; 🇫🇷 Montigny-Le-Bretonneux, France