ESPE Abstracts

Objective: The Triac Trial I was a multicentre, open-label, single-arm, Phase II study of tiratricol (triac) in the treatment of monocarboxylate transporter 8 (MCT8) deficiency. The study demonstrated the beneficial effect of tiratricol in alleviating peripheral thyrotoxicosis. A subset of patients entered the study whilst having a feeding tube. Here, we investigate the impact of the presence of a feeding tube on tiratricol dosing and reaching the serum total T3 (TT3) target range.

Methods: Study methods have been reported previously. Briefly, after an initial dose of 350 µg tiratricol daily, patients underwent progressive dose escalation in 350 µg increments until a serum TT3 concentration of 1.4–2.5 nmol/L (target range) was achieved. This was the tiratricol maintenance dose, which was continued, provided serum TT3 concentrations remained in the target range. Study outcomes were assessed at baseline and 12 months. Patients were stratified post hoc based on the presence (Group 1) or absence (Group 2) of a feeding tube at the start of the study. None of the participants underwent placement of a feeding tube during the study. All analyses were performed on the intention-to-treat (ITT) population, which comprised all patients who received ≥1 dose of study medication and who provided ≥1 non-missing post-treatment observation for serum TT3 concentration. Within-group mean changes from baseline to Month 12 were analyzed using 95% confidence intervals.

Results: Patients with feeding tubes had higher weight and weight-for-age at baseline; serum TT3 was no different. The mean tiratricol maintenance dose was 39.7 µg/kg (95% Confidence Intervals [CI] 30.7-48.7) in Group 1 (n = 17) and 36.2 µg/kg (95%CI 30.3-42.2) in Group 2 (n = 26), indicating patients using a feeding tube required similar doses of tiratricol to reach serum target TT3 range. Mean serum TT3 concentrations decreased by 3.24 nmol/L (95%CI 2.40-4.09) in Group 1 (n = 19) and 3.08 nmol/L (95%CI 2.50-3.66) in Group 2 (n = 26) between baseline and Month 12. Mean body weight and weight-for-age both increased between baseline and Month 12 in both groups: mean body weight increased 2.61 kg (95%CI 0.84-4.38) in Group 1 (n = 19) and 2.19 kg (95%CI 1.29-3.08) in Group 2 (n = 26); mean body weight-for-age increased by 0.28 (95%CI 0.17-0.72) in Group 1 (n = 19) and 0.18 (95%CI -0.08-0.45) in Group 2 (n = 26; P = 0.16).

Conclusions: Tiratricol was effective at decreasing serum TT3 concentrations and increasing body weight in patients with MCT8 deficiency, with or without the presence of a feeding tube.