Phase 1 Trial Indicates Liquid Formulation of Levothyroxine Safe to Administer as Early as 15 Minutes Before Breakfast

Data from a phase 1 trial comparing dosing 15 and 30 minutes prior to breakfast suggests the wait time between intake of the novel liquid formulation of levothyroxine, Tirosint-SOL, and breakfast could be shortened to 15 minutes.

New research presented at the American Academy of Clinical Endocrinology 30th Annual Meeting (AACE 2021) suggests levothyroxine sodium (Tirosint-SOL) oral solution can be safely administered as early as 15 minutes before breakfast.

A single-center, open-label, crossover study, results indicate the absorption profile of levothyroxine sodium was clinically equivalent when administered 30 or 15 minutes prior to a high-fat, high-calorie breakfast.

"Levothyroxine is a narrow therapeutic index (NTI) drug that requires no interference from food or beverages for consistent dissolution and absorption", said Murray Ducharme, PharmD, visiting professor at the University of Rhodes, in a statement from IBSA Pharma. "The results of this study demonstrate that the wait time needed before breakfast may be shortened to a period of 15 minutes without significant negative effect with the liquid levothyroxine formulation."

With levothyroxine a cornerstone in treatment algorithms for patients with hypothyroidism, Ducharme and a team of colleagues sought to learn more about how the delivery method of levothyroxine sodium might impact the absorption process compared to tablets or soft gel formulations. With this in mind, investigators designed their study as a single-center, phase 1, open-label, randomized, single-dose, 2-period, 2-sequence, crossover trial in 36 healthy volunteers.

The 36 study participants were administered 600 mcg of levothyroxine sodium after a 10-hour overnight fast and 15 or 30 minutes prior to a high-fat, high-caloric meal. For the purpose of analysis, serum concentrations of levothyroxine were measured using a validated LC-MS method serum samples were taken at 3 different times before dosing and at 0.5, 1, 1.5, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours after dosing.

Of note, the meal used in the study consisted of 2 eggs fried in butter, 2 strips of bacon, 2 slices of toast with butter, 120 g of hash brown potatoes, and 200 mL of whole milk.

Of the 36 patients included in the study, 36 completed all study periods. The 3 who did not complete the trial failed to do so because of failure to undergo COVID-19 testing, vomiting within 6 hours of dosing, and failure to complete the meal.

Upon analysis, results indicated the median Tmax was unchanged between the treatment arms at 1.5 hours. Investigators pointed out the geometric mean ratios and confidence intervals for the baseline adjusted maximum and extent of exposure were within recognized equivalence boundaries, which indicates an absence of meaningful clinical difference when dosing 15 or 30 minutes prior to a meal.

Investigators also noted there were no differences in adverse events and a total of 11 treatment-emergent adverse events were reported during the trial. Of the 11 events reported, 10 were graded as mild and 1 was graded as moderate. Additionally, 6 were considered possibly related, 1 was considered unlikely related, and 4 were unrelated. No deaths occurred and none of the adverse events that occurred during the trial were considered significant.

This study, “A novel solution of Levothyroxine results in clinically similar maximum and extent of exposure whether taken 30 or just 15 minutes before a High-Fat High-Caloric breakfast,” was presented at AACE 2021.