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P581 A Pharmacokinetic Study of Ferric Maltol (ST10; Fe-M) at 3 Dosages in Inflammatory Bowel Disease (IBD) Patients with Iron Deficiency

B. Bokemeyer*1, A. Krummenerl2, C. Maaser3, S. Howaldt4, M. Mroß5, N. Mallard6

1Gastroenterology Practice Minden, Gastroenterology , Minden, Germany, 2Krankenhaus Martha-Maria Halle-Dölau, Studienambulanz, Klinik für Innere Medizin I, Halle (Saale), Germany, 3Städtisches Klinikum Lüneburg gGmbH, Leitung Ambulanzzentrum Gastroenterologie am Klinikum Lüneburg, Lüneburg, Germany, 4Hamburgisches Forschungsinstitut für CED, HaFCED GmbH&Co. KG, Hamburg, Germany, 5Gastroenterologische Spezialpraxis, Gastroenterologische, Berlin, Germany, 6Iron Therapeutics (UK) Ltd, Clinical Development, Gateshead, United Kingdom

Background

Fe-M (ST10) is a novel Fe3+ form of iron that has been shown to be well tolerated in IBD patients unable to use ferrous sulphate, and successfully correct Iron Deficiency Anaemia (IDA) at a 30mg twice a day (bid) dose (AEGIS 1 & 2). This study examined whether higher doses would result in greater iron absorption.

The aim was to investigate the single and repeat dose kinetics of iron and maltol components of Fe-M in IBD patients with iron deficiency.

Methods

Eligible patients were adults with IBD and iron deficiency, defined by ferritin <30 µg/L, or ferritin <50 µg/L and transferrin saturation (TSAT) <20%; and haemoglobin (Hb) ≥ 8.5 g/dL. Patients were randomised to Fe-M oral capsules 30, 60 or 90 mg bid for Days 1 to 8; taken on an empty stomach. PK blood and urine samples were collected after the first morning dose Day 1 and after a final dose morning Day 8.

Results

24 IBD patients (UC: 11; CD 13; mean age: 39 y; 66% female; mean baseline ferritin 13.9ug/L; TSAT 17.9%; serum iron 12.5umol/L; Hb 13g/dL) were randomised.

For all doses plasma concentrations of maltol and maltol glucuronide (maltol-G) increased rapidly, reaching Cmax 1-1.5 hours post dose, declining to baseline after 3 and 6 hours. Exposure to maltol G was higher compared to maltol. Urine PK showed maltol is rapidly excreted as maltol G. Serum iron and TSAT increased after dosing, with maximum values between 1.5-3 hours post dose for all groups; the PK profiles were similar on Days 1 and 8.

Day 1 TSAT increase from baseline was higher in the 60 and 90mg groups compared to the 30mg (57.4 and 54.7 vs 24.8%). Ferritin increased in all groups by Day 8, but was greater in the 60 and 90mg groups (15.7 and, 17.1 vs 7.22µg/L). Reticulocyte Hb increased in all groups by Day 8; the rise was greater in the 60 and 90mg groups compared to the 30mg (3.37 and 3.07 vs 0.92pg).

The most common adverse events (AEs) were GI (7 subjects, 29.2%); non IBD-related GI AEs were more frequent in the 90mg group (57.1% of subjects vs 11.1% and 25.0% for 30 and 60mg). AEs were of mild or moderate intensity. Diarrhoea and abdominal pain were the most commonly reported AEs (12.5% and 8.3% of subjects).

Conclusion

The PK data from this study are consistent with previous data indicating that maltol is rapidly glucuronidated after Fe-M dosing, while iron is independently absorbed. 30mg Fe-M (ST10) has been shown to be well tolerated and effective in correcting IDA; however results of this study show 60mg bid resulted in greater iron absorption as evidenced by TSAT, ferritin and reticulocyte Hb rise. Additional clinical studies are needed to see if this would result in a more rapid Hb increase in IDA subjects.