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Randomized Open-Label Phase 1 Study of the Pharmacokinetics of Ferric Maltol in Inflammatory Bowel Disease Patients with Iron Deficiency

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Abstract

Background

Iron deficiency anemia (IDA) is a common complication of inflammatory bowel disease (IBD). Oral ferric maltol improves and normalizes hemoglobin (Hb) in patients with IBD.

Aim

This open-label, randomized Phase 1 study evaluated the pharmacokinetics of ferric maltol and its effect on iron indices in IBD patients with iron deficiency (with or without anemia).

Methods

Iron deficient adult IBD patients received ferric maltol 30, 60, or 90 mg twice daily during an 8-day period. Pharmacokinetics and iron uptake were assessed on days 1 and 8.

Results

Twenty-four patients were included: 13 with Crohn’s disease and 11 with ulcerative colitis (mean age 39 years; 67 % female, mean Hb 13.0 g/dL; mean reticulocyte Hb content (CHr) 31.9 pg; mean ferritin 13.9 µg/L). Plasma maltol and maltol glucuronide increased rapidly at all doses, reaching maximum plasma concentration (C max) 1.0–1.5 h post-dose and declining to baseline after 3–6 h. Maltol and maltol glucuronide exposure (area under the concentration–time curve; AUC) appeared dose proportional with twice-daily dosing, with higher exposure to maltol glucuronide vs. maltol. Mean day 8/day 1 ratios for C max and AUC0–t indicated no accumulation after 7 days of twice-daily dosing. Serum iron and transferrin saturation (TSAT) increased with all doses (maximum values at 1.5–3.0 h post-dose). Serum ferritin and CHr increased by day 8, with greater improvements with 60 and 90 mg twice-daily doses than with 30 mg twice-daily doses.

Conclusions

The key constituents of ferric maltol showed predictable pharmacokinetics, with no accumulation over 7 days and increased iron uptake and storage over time at 30–90 mg twice-daily doses.

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Acknowledgments

Matthew Reilly, PhD, at InTouch Medical Ltd provided editorial support in the preparation of this manuscript, paid for by Shield TX (UK) Limited, and had access to all study data.

Author contributions

As principal investigator, BB oversaw the clinical research, helped collect the data and acted as guarantor for the manuscript. AK, CM, SH and MM contributed clinical data and provided critical input on the manuscript. NM helped design the study, oversaw clinical data management and analysis, and contributed critical input to the manuscript. All authors had access to the study data and approved the final version of the manuscript prior to submission.

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Authors and Affiliations

  1. Gastroenterology Practice Minden, Uferstr. 3, 32423, Minden, Germany

    Bernd Bokemeyer

  2. Krankenhaus Martha-Maria Halle-Dölau, Klinik für Innere Medizin I, Halle (Saale), Germany

    Annette Krummenerl

  3. Städtisches Klinikum Lüneburg, Ambulanzzentrum Gastroenterologie am Klinikum Lüneburg, Lüneburg, Germany

    Christian Maaser

  4. Schwerpunktpraxis CED, Hamburg, Germany

    Stefanie Howaldt

  5. Gastroenterologische Schwerpunktpraxis, Berlin, Germany

    Michael Mroß

  6. Clinical Development, Shield TX (UK) Limited, Gateshead, UK

    Nick Mallard

Authors
  1. Bernd Bokemeyer
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  2. Annette Krummenerl
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  3. Christian Maaser
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  4. Stefanie Howaldt
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  5. Michael Mroß
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  6. Nick Mallard
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Corresponding author

Correspondence to Bernd Bokemeyer.

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Funding

This research was funded in full by Iron Therapeutics Ltd, UK.

Conflict of interest

BB has received consultancy fees from Abbvie, MSD, Shire, Ferring, UCB, Hospira, Takeda, Movetis and Shield TX (UK) Limited, speaker honoraria from Abbvie, Ferring, MSD, Merckle, Falk, HLR and UCB, and research funding from Abbvie, Ferring and UCB. NM is an employee of Shield TX (UK) Limited. SH has received consulting fees and travel expenses from Shield TX (UK) Limited. AK, CM and MM have no conflicts of interest to declare.

Ethical approval

The study protocol was approved by the responsible independent ethics committees, and all procedures were conducted according to the Declaration of Helsinki, the International Conference on Harmonization guidelines on Good Clinical Practice and applicable national and regional laws and regulations.

Informed consent

Written informed consent was obtained from each patient prior to participation.

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Bokemeyer, B., Krummenerl, A., Maaser, C. et al. Randomized Open-Label Phase 1 Study of the Pharmacokinetics of Ferric Maltol in Inflammatory Bowel Disease Patients with Iron Deficiency. Eur J Drug Metab Pharmacokinet 42, 229–238 (2017). https://doi.org/10.1007/s13318-016-0334-5

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  • DOI: https://doi.org/10.1007/s13318-016-0334-5

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