Abstract
This multiple-dose Phase I/II study provided pharmacodynamics and pharmacokinetics
data on the therapeutic benefit of ferric carboxymaltose (FCM, Ferinject® ) and evaluated the safety and tolerability of this intravenous (i. v.) iron preparation.
Two doses of iron as FCM were given as i.v. infusion over 15 min, 500 mg iron given
once weekly for up to 4 weeks (Cohort 1) or 1000 mg iron weekly for 2 weeks (Cohort
2), in patients with a total requirement ≥ 1000 mg iron (total cumulative maximum
dose ≤ 2000 mg iron). Adults with moderate to severe, stable iron-deficiency anaemia
(IDA) (haemoglobin [Hb] ≤11.0 g/dl, serum ferritin <100 µg/l, transferrin saturation
[TSAT] <16%) due to a gastrointestinal (GI) disorder were included. Pharmacodynamics
variables: proportion of patients achieving values within the reference range for
Hb (men: 14.0–18.0 g/dl, women: 12.0–16.0 g/dl), serum ferritin (20–500 µg/1), TSAT
(16–45%) and proportion of patients with an increase in Hb of at least 2.0 g/dl. Pharmacokinetics
variables: total serum iron levels at time of maximum serum iron concentration during
the fast elimination phase and at trough time-points. Safety assessments: the incidence
of adverse events (AEs) and changes in vital signs, physical examinations, and clinical
laboratory parameters. In Cohorts 1 and 2, 14/20 (70%) versus 19/26 (73%) of patients
completed the study. Individual calculated iron deficits were 1000–2100 mg. The mean
cumulative dose of FCM in Cohorts 1 and 2 was 1800 mg and 1563 mg iron, respectively.
At baseline, patients in both cohorts had similar Hb levels (mean 8.7 g/dl in both
cohorts). More than 97% of patients demonstrated a clinically meaningful increase
in Hb levels (≥ 1.0 g/dl) during the study. By the week 4 follow-up visit, an increase
of at least 2.0 g/dl was achieved by 15/20 (75%) and by 19/26 (73.1%) patients in
Cohorts 1 and 2, respectively, and the mean increase in Hb was 3.2 g/dl in Cohort
1 and 3.3 g/dl in Cohort 2. By day 28, 3/6 (50%) patients in Cohort 1 had achieved
normal Hb levels, and by the 4-week post-treatment follow-up visit 7/19 patients (37%)
in Cohort 1 and 12/25 (48%) in Cohort 2 had reached Hb levels within the reference
range. Serum ferritin levels increased rapidly at the start of treatment and remained
in the reference range throughout the study; increases were greater in Cohort 2. Mean
baseline TSAT values were similar in both cohorts (24.2% in Cohort 1, 20.7% in Cohort
2), and were within the reference range at the week 4 follow-up visit for 41.0 and
39.1% of the patients in Cohorts 1 and 2, respectively. The incidence of AEs occurring
after the first administration of FCM (treatment-emergent AEs, TEAE) was generally
low and similar in Cohorts 1 (11/20 [55.0%]) and 2 (13/26 [50.0%]). Most TEAEs were
mild; only 2/20 patients (10.0%) in Cohort 1 and 3/26 (11.5%) in Cohort 2 had TEAEs
of moderate intensity. There were no AEs of severe intensity, serious AEs, or deaths.
Most AEs were considered by the investigator to be unrelated or unlikely to be related
to the study medication. Since accumulation of serum iron was not observed, a dosing
interval of 3–4 days (500 mg iron) or 1 week (1000 mg iron) was demonstrated to be
adequate. The increase in serum ferritin and TSAT at the 4-week follow-up visit is
indicative of a repletion of the iron stores. The results suggest that doses up to
1000 mg i. v. iron administered as FCM over 15 min are well tolerated and effective
in the treatment of patients with IDA due to a GI disorder.
Key words Anaemia - Crohn’s disease - Ferinject® - Ferric carboxymaltose - Inflammatory bowel
disease - Intravenous iron - Iron deficiency
