Thorough cardiac QTc interval conductance assessment of a novel oral tranexamic acid treatment for heavy menstrual bleeding.
OBJECTIVE
To assess the effect of a novel oral tranexamic acid treatment on cardiac repolarization in a randomized, double-blind, positive- and placebo-controlled, four-treatment single-dose cross-over inpatient study.


METHODS
QTc interval and drug exposure relationship analyses were performed using triplicate digital electrocardiographs (ECGs) collected from 12-lead Holter monitors from healthy females (n = 48) with plasma drug concentrations and pharmacokinetics simultaneously evaluated over 24 h post-dose. Therapeutic (1.3 g) and supratherapeutic (3.9 g) tranexamic acid modified immediate-release doses, a positive-control 0.4 g moxifloxacin dose, and a placebo-control were administered at each period.


RESULTS
All post-dose, time-matched, baseline-adjusted, mean QTcF (Fridericia's heart rate correction, QT/RR(1/3)) treatment-placebo differences (DeltaDeltaQTcF), were less than 5 milliseconds (ms) for the 1.3 g and 3.9 g tranexamic acid doses. Upper limits of the 95% confidence interval (CI) for all tranexamic acid-placebo DeltaDeltaQTcF doses were < 10 ms for all time points. Lower limits of the 95% CI for the positive-control (moxifloxacin-placebo) DeltaDeltaQTcF were > 5 ms at multiple time points demonstrating assay sensitivity. No correlation between tranexamic acid plasma concentrations and adjusted QTc intervals was observed. A positive linear relationship was observed for moxifloxacin (p < 0.01).


CONCLUSIONS
Cardiac repolarization is not influenced by tranexamic acid at the doses studied.
Moore
Keith A
KA
Xanodyne Pharmaceuticals, Inc., Clinical Research & Product Development, One Riverfront Place, Newport, KY 41071-4563, USA. kmoore@xanodyne.com
Callahan
Timothy S
TS
Maison-Blanche
Pierre
P
Morin
Isabelle
I
Marenco
Ted
T
Swearingen
Dennis
D
Olbertz
Joy
J
D000284:Administration, Oral; D000328:Adult; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D024841:Fluoroquinolones; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008595:Menorrhagia / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000933:Antifibrinolytic Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D014148:Tranexamic Acid; D000077266:Moxifloxacin