Abstract
Background
Sibofimloc (EB8018/TAK-018) is a gut-restricted orally administered, first-in-class, FimH blocker that targets FimH, a TLR4 receptor, expressed on E. coli and other Enterobacteriaceae in patients with CD. In a previous study, sibofimloc up to 1500 mg twice daily was well tolerated when administered to healthy subjects over a 14-day period. PK results indicated that sibofimloc was detectable in plasma at a very low level. The current study investigated the PK, safety, and pharmacodynamic effects of sibofimloc following 13 days of 1500 mg twice daily oral administration in patients with CD. Objectives of this study were to determine the PK (primary) and safety profiles, effects on inflammatory biomarkers, gut microbiome and on stool frequency and pain score.
Methods
We conducted a multicenter open-label study to enrol 8 adult patients with active CD (faecal calprotectin (FCP) ≥150 µg/g and/or ulcers at colonoscopy). Pregnant women were excluded. This study was divided into two parts. 1)Two patients received a single dose of 3000 mg sibofimloc followed, after a wash-out period, by a 13 day-period with1500 mg twice daily. 2)After review of data from these two patients, the 6 remaining patients received 1500 mg sibofimloc twice daily for a 13 day period.
Results
Cmax values for the 2 initial patients (after single dose 3000 mg sibofimloc) were 51.3 and 348 ng/ml respectively and allowed part 2 of the study. The main safety and PK data of an interim analysis after the first 4 patients had been treated with sibofimloc 1500 mg twice daily are presented in the table.
In a previous study in 7 healthy subjects, after 14 days sibofimloc 1500 mg twice daily, median Cmax[min-max] at Day14 was 49[19.2–86.6]ng/ml.
Conclusion
These preliminary data confirmed that sibofimloc was well tolerated. In the small subset of patients analyzed, there was a slightly higher plasma exposure and interpatient variability compared with what has been seen earlier in healthy subjects. The safety and PK data allowed the continuation of the clinical development program with the initiation of a phase 2 trial for postoperative maintenance in patients with CD.
Randomized, Open‐Label, Single‐Dose, Parallel‐Group Pharmacokinetic Study of PF‐06410293 (adalimumab‐afzb), an Adalimumab Biosimilar, by Subcutaneous Dosing Using a Prefilled Syringe or a Prefilled Pen in Healthy Subjects
