PII-029 - PHARMACOKINETIC EVALUATION OF GB1211 IN A NOVEL TABLET FORMULATION, ADMINISTERED UNDER FASTED AND FED CONDITIONS, AND COMPARED TO GB1211 CAPSULES, IN HEALTHY VOLUNTEERS

P. Dogterom¹, K. Abd-Elaziz¹, S. Pan², W. Morley³, L. Gravelle³, B. Lindmark³, A. Brinch³, V. Aslanis³; ¹QPS Netherlands, ²QPS Taiwan, ³Galecto.

Background: GB1211 is an orally available small molecule, which reversibly inhibits galectin-3. Galectin-3 is involved in inflammation and fibrosis and the development of various cancers.
In the first in-human study, GB1211 has been administered as capsules of different strengths. Ultimately, a 50 mg capsule was selected for use in the ongoing patient studies. The effect of food on this formulation was minimal, causing only a delay in the absorption by about 2 hours (h) without affecting systemic exposure. A new, 100 mg strength tablet formulation is available and had to be tested pharmacokinetically prior to use in further patient studies.

Methods: The study was an open label, randomized, single oral dose, three period crossover study in 12 (planned) healthy male and female subjects. The wash-out between successive dosing occasions was 14 days. GB1211 100 mg was dosed as one tablet under fasting conditions, one tablet under fed conditions and two capsules of 50 mg each under fasting conditions.
Blood samples and all urine (only during the first period) for the bioanalysis of GB1211 were collected up to 96 hours after any dosing.
Standard and well established PK evaluation programs were used to calculate PK parameters for comparing the various treatments.

Results: Under fasting conditions, mean Cmax and AUC0-inf of GB1211 were respectively 161% and 84% higher after intake of a tablet versus capsules. Absorption of GB1211 was slightly faster upon dosing of the tablet with median Tmax values of 2.02 h (tablet) and 3.06 h (capsule). This shorter absorption duration was counteracted by food since under fed conditions the median Tmax was about 5 h. Mean Cmax was 20% lower whereas AUC0-inf was not affected by food.
Urinary excretion of unchanged GB1211 was about 15% of the dose (capsule, fasting) whereas it was doubled (about 30%) or even slightly more than doubled (about 36%) after a tablet under fasting and fed conditions, respectively.
Irrespective of the treatment, its conditions and some differences in the PK results, GB1211 exhibited a favorable safety and tolerability profile.

Conclusion: The novel tablet formulation of the oral galectin-3 inhibitor GB1211 has a higher exposure than capsules, and the effect of food on its PK is minimal. This GB1211 tablet could provide a more convenient drug intake, as well as once-daily dosing.