Ferric trimaltol for use in treating or preventing iron deficiency in a human patient with or without anaemia

Abstract

The invention relates to the use of ferric trimaltol for treating or preventing iron deficiency, with or without anaemia, in human patients aged 1 month to less than 2 years. The ferric trimaltol is a

Description

This invention relates to ferric trimaltol for use in treating or preventing iron deficiency in a human patient with or without anaemia, wherein the ferric trimaltol is administered orally, wherein the patient is aged 1 month to less than 2 years old. It is known that ferric maltol is not absorbed on ingestion by the human body as an intact complex. Upon dissociation of the complex, the maltol molecules are absorbed and glucuronidated in the intestinal wall, and within the liver during first pass metabolism catalyzed by UDP (uridine 5'-diphospho-) glucuronyl transferase (UGT), and subsequently eliminated from the body in urine. The iron is absorbed via the endogenous dietary iron uptake system (Bokemeyer et al. ('Randomized Open-Label Phase 1 Study of the Pharmacokinetics of Ferric Maltol in Inflammatory Bowel Disease Patients with Iron Deficiency', European Journal of Drug Metabolism and Pharmacokinetics, 2017 Apr; 42(2):229-238)). It is known that the processes involved in the elimination of maltol (metabolism and renal excretion) are subjected to the maturation processes on UGT enzyme activity and glomerular filtration rate. It has been shown that renal function only reaches full maturation by 2-3 years old humans (Anderson, 'Children Versus Adults: Pharmacokinetic and Adverse-Effect Differences', Epilepsia, 43(Suppl. 3):53-59, 2002). An in vitro drug:drug interaction study (Tomlinson and Ford, XenoGesis Ltd, 'Uridine 5'-diphospho-glucuronosyltransferase (UGT) phenotyping against the 7 major human UGTs with a single test article (maltol) using UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7 and UGT2B15 Corning®Supersomes™', 2016- unpublished) was conducted to establish the specific (protein) isoform that metabolizes maltol in humans. This unpublished study confirmed that UGT1A6 was the isoform responsible for glucuronidation of maltol. It is known that this isoenzyme does not mature until around 14 months of age in humans (Miyagi S. J., Collier A. C. (2011), 'The development of UDP-glucuronosyltransferases 1A1 and 1A6 in the pediatric liver', Drug Metab. Dispos., 39, 912-919). Summary of the invention Thus, it was not expected that ferric trimaltol could be safely administered to humans below 2 years of age as it was thought that their digestive and renal organs have not matured sufficiently to process maltol and excrete maltol glucuronide. Surprisingly, the inventors have observed through their recent studies that this is not the case. Therefore, in a first aspect of the invention, ferric trimaltol for use in treating or preventing iron deficiency in a human patient with or without anaemia is provided, wherein the ferric trimaltol is administered orally, wherein the patient is aged 1 month to less than 2 years old, preferably 1-23, 3-23, 6-23, 9-23, 11-23, 9-21, 9-18, 10-18, or 11-18 months old. By the term 'treating iron deficiency' is meant eliminating or reducing iron deficiency. In a second aspect of the invention, use of ferric trimaltol for the manufacture of a medicament for treating or preventing iron deficiency in a human patient with or without anaemia is provided, wherein the ferric trimaltol is administered orally, wherein the patient is aged 1 month to less than 2 years old, preferably 1-23, 3-23, 6-23, 9-23,11-23, 9-21, 9-18,10-18, or 11-18 months old. In a third aspect of the invention, a method for treating or preventing iron deficiency in a human patient with or without anaemia is provided, wherein an effective amount of ferric trimaltol is administered orally, wherein the patient is aged 1 month to less than 2 years old, preferably 1-23, 3-23, 6-23, 9-23, 11-23, 9-21, 9-18, 10-18, or 11-18 months old. Detailed description of the invention In a first aspect of the invention, ferric trimaltol for use in treating or preventing iron deficiency in a human patient with or without anaemia is provided, wherein the ferric trimaltol is administered orally, wherein the patient is aged 1 month to less than 2 years old, preferably 1-23, 3-23, 6-23, 9-23, 11-23, 9-21, 9-18, 10-18, or 11-18 months old. Ferric trimaltol or ferric maltol is a chemically stable complex formed between ferric iron (Fe3+) and maltol (3-hydroxy-2-methyl-4-pyrone) according to the chemical structure below: The molar ratio of iron to hydroxypyrone is 1:3. Maltol is a naturally occurring sugar derivative and is used in the food industry as a flavour enhancer. Preferably, the ferric trimaltol is administered orally in the form of a liquid composition or liquid suspension composition. The ferric trimaltol may be in the form of a liquid composition or a liquid suspension composition. The term 'liquid composition' includes a solution of ferric trimaltol in a solvent, such as water, an oil and / or an alcohol, or other pharmaceutically acceptable liquid. The term 'liquid composition' can also encompass emulsions such as oil-in-water liquid emulsions, water-in-oil liquid emulsions, or multiple emulsions. The term 'liquid composition' also encompasses a semi-fluid composition or a semisolid composition. A semisolid composition typically does not hold its shape like a solid but does not flow like a liquid. Examples of semisolid compositions outside the scope of the invention include, for example, foodstuffs such as yoghurt or mayonnaise. The term 'liquid suspension composition' means a composition which comprises a suspension of ferric trimaltol in a liquid medium, for example an aqueous or non-aqueous liquid such as an oil and / or an alcohol, or other pharmaceutically acceptable liquid. The liquid suspension composition may also comprise dissolved ferric trimaltol. The ferric trimaltol may be visible as suspended particles. In one embodiment of the invention, the pH of the liquid composition or liquid suspension composition is controlled to, for example, stabilize the ferric trimaltol. For example, the composition may include an acidity regulator, such as a buffer. For example, the pH of the liquid composition or liquid suspension composition may advantageously be about 6 to about 8, for example from about 6.5 to about 7.5. In another embodiment of the invention, where the pH of the liquid composition or liquid suspension composition is less than about 7, such as when buffered by citric acid / Na citrate, then the addition of further maltol will reduce disproportionation and ensure that the ferric trimaltol in the composition is mainly a 1:3 chelate. The ferric trimaltol may be present in the liquid composition or liquid suspension composition at a concentration of from about 0.6 to about 60, from about 0.3 to about 20, from about 1 to about 10, preferably about 6 mg / ml ferric iron equivalent. In one embodiment of the invention, the liquid composition or liquid suspension composition comprises a sweetening agent. The sweetening agent may be a saccharide or non-saccharide sweetening agent. Suitable sweetening agents include, for example, one or more of aspartame, stevia-based sweetener extract, saccharin, refined sugar, sucralose, neohesperidine dihydrochalcone and hesperidine dihydrochalcone 4'-beta-D-glucoside, or mixtures thereof. The sweetening agent may be present in the liquid composition or liquid suspension composition in an amount of from about 0.1 to about 70 percent (w / v), or from about 1 to about 60 percent (w / v), such as from about 5 to about 40 percent (w / v) or from about 5 to about 20 percent (w / v) or from about 5 to about 10 percent (w / v) based on the total volume of the liquid composition or liquid suspension composition. In one embodiment of the invention, the liquid composition or liquid suspension composition comprises a sweetness enhancer. One example of a suitable sweetness enhancer is a maltol. This may be added separately from the ferric trimaltol. The sweetness enhancer preferably comprises maltol or ethyl maltol, or combinations thereof. The sweetness enhancer may be present in the liquid composition or liquid suspension composition in an amount of from about 0.1 to about 15 percent (w / v), or from about 0.2 to about 10 percent (w / v) or from about 1 to about 5 percent (w / v) based on the total volume of the liquid composition or liquid suspension composition. In another embodiment of the invention, the liquid composition or liquid suspension composition further comprises a flavouring agent. The flavour may be any suitable flavour. The flavour may, for example, be selected from the group consisting of apple, blackcurrant, orange, lemon, grape, maple, raspberry, cherry, menthol, peppermint, spearmint, vanilla, chocolate, strawberry and combinations thereof. The amount of the flavouring agent may be from about 0.01 to about 15 percent (w / v), or from about 0.02 to about 10 percent (w / v) or from about 0.1 to about 5 percent (w / v) based on the total volume of the liquid composition or liquid suspension composition. In another embodiment of the invention, the liquid composition or liquid suspension composition further comprises a preservative. The flavour may, for example, be selected from the group consisting of potassium nitrate, erythorbic acid, benzoic acid, sodium benzoate, potassium sorbate, calcium sorbate and combinations thereof. The amount of the flavouring agent may be from about 0.01 to about 5 percent (w / v), or from about 0.02 to about 2 percent (w / v) or from about 0.1 to about 1 percent (w / v) based on the total volume of the liquid composition or liquid suspension composition. In another embodiment of the invention, the liquid composition or liquid suspension composition further comprises a surfactant. The surfactant may, for example, be selected from the group consisting of alkyl glycosides, carrageenan (carbohydrate), cholesterol, lanolin, lecithin, monoglycerides (fatty acid), phytosterols, proteins, Polysorbate 80, tea saponin extract and combinations thereof. The amount of the surfactant may be from about 0.01 to about 5 percent (w / v), or from about 0.02 to about 2 percent (w / v) or from about 0.1 to about 1 percent (w / v) based on the total volume of the liquid composition or liquid suspension composition. In another embodiment of the invention, the liquid composition or liquid suspension composition further comprises a viscosity modifier such as xanthum gum. These tend to often be the same as suspending agents as described hereinbelow and are used at similar concentrations. In another embodiment of the invention when the composition is or comprises a liquid suspension composition, the liquid suspension composition further comprises a suspending agent. A suspending agent helps to reduce the sedimentation rate of particles in suspension. Suitable examples of suspending agents include methylcellulose, polyvinylpyrrolidone, carboxymethyl cellulose, sodium alginate or povidone and combinations thereof. The amount of the suspending agent may be from about 0.01 to about 15 percent (w / v), or from about 0.02 to about 10 percent (w / v) or from about 0.1 to about 5 percent (w / v), or from about 0.1 to about 2 percent (w / v) based on the total volume of the liquid suspension composition. In one embodiment of the invention, the method of forming the liquid composition or the liquid suspension composition comprises combining ferric trimaltol and other dry ingredients, preferably in a solid or dry form, such as a powder, with a liquid. Alternatively, the ferric trimaltol and other dry ingredients may be combined separately with the liquid, such as water or an oil. In one embodiment the iron deficiency is iron deficiency with or without anaemia resulting from one or more of the group consisting of nutritional deficiency, kidney disease, coeliac disease and other malabsorption disorders, inflammatory bowel disease (IBD) and cancer. Preferably kidney disease does not include chronic renal disease (estimated Glomerular Filtration Rate (eGFR) <60 mL / min / m2), as assessed at Screening based on serum creatinine (see hereinbelow under Exclusion Criteria). In one embodiment the inflammatory bowel disease is Crohn's disease. In one embodiment, the Crohn's disease is not active. By the term 'not active' is meant for Crohn's disease a Crohn's Disease Activity Index (CDAI) of <220. In another embodiment of the invention, the inflammatory bowel disease may be ulcerative colitis. In one embodiment, the ulcerative colitis is not active. By the term 'not active' is meant for ulcerative colitis a Simple Clinical Colitis Activity Index (SCCAI) value of <4. The ferric trimaltol is preferably administered at an about 0.06 to about 1.2, about 0.3 to about 0.9, about 0.6 mg / kg body weight ferric iron equivalent dose twice a day. Preferably the ferric trimaltol is administered once in the morning and once during the evening. By the term 'morning' is meant the period of time from midnight to noon. By the term 'evening' is meant the period of time from about 18:00 to midnight. Preferably, the ferric trimaltol is administered for at least 24, 20,16,15,14, 13,12, 8, 4 weeks. Optionally, the ferric trimaltol is subsequently administered at an about 0.06 to about 1.2, about 0.3 to about 0.9, about 0.6 mg / kg body weight ferric iron equivalent dose once or twice a day. Subsequent administration may be of indefinite term as a maintenance dose. In one embodiment, the ferric trimaltol is administered on an empty stomach. Alternatively, in another embodiment the ferric trimaltol is administered on a full or partially full stomach which means where the ferric trimaltol is administered up to 4, 3, 2, 1, 0.5 hours before or after or simultaneously with solid and / or liquid food. In a second aspect of the invention, use of ferric trimaltol for the manufacture of a medicament for treating or preventing iron deficiency in a human patient with or without anaemia is provided, wherein the ferric trimaltol is administered orally, wherein the patient is aged 1 month to less than 2 years old, preferably 1-23, 3-23, 6-23, 9-23,11-23, 9-21, 9-18,10-18, or 11-18 months old. In a third aspect of the invention, a method for treating or preventing iron deficiency in a human patient with or without anaemia is provided, wherein an effective amount of ferric trimaltol is administered orally, wherein the patient is aged 1 month to less than 2 years old, preferably 1-23, 3-23, 6-23, 9-23, 11-23, 9-21, 9-18, 10-18, or 11-18 months old. The various embodiments, options, and preferred features of the first aspect of the inventions set forth hereinabove are equally applicable to the second and third aspects of the invention. Example: Title of study: Randomised, open-label, active-controlled, multicentre, study to evaluate the safety and efficacy of ferric maltol (iron (lll)-maltol complex) in an oral liquid suspension composition in infants aged 1 month to less than 2 years. Ferric maltol makes iron available in the gastrointestinal tract, providing the iron in a biologically labile form for uptake across duodenal mucosal cells and ultimate haematopoiesis and storage on ferritin. Primary objectives: 1. To assess the safety and tolerability of a ferric maltol oral liquid suspension composition in children 1 month to less than 2 years, in the treatment of iron deficiency anaemia during a 12 weeks treatment period. 2. To assess the effect on haemoglobin (Hb) in children aged 1 month to less than 2 years after twice daily ferric maltol oral suspension administration for 12 weeks. Secondary objectives: 1. To assess the pharmocokinetics in children aged 1 month to less than 2 years of age after a single dose of ferric maltol oral liquid suspension composition (Pre-assignment PK visit) and after twice daily administration for at least 6 days, on Visit 3 (PK Day 2) after a single morning dose, through measurement of plasma (PK Day 2 only) and urine concentration of maltol and maltol glucuronide. Primary endpoints: 1. Safety and gastrointestinal tolerability (Treatment emergent Adverse Events (TEAEs); Treatment-emergent Serious Adverse Events (TESAEs)). 2. Treatment-emergent Adverse Events leading to premature discontinuation of study drug / pharmacokinetic (PK) assessments from baseline to Week 12. 3. Change in haemoglobin (Hb) concentration from baseline to Week 12. Secondary endpoints: 1. PK analysis of maltol and maltol glucuronide in plasma in children aged 1 month to less than 2 years in the ferric maltol group. 2. Age 1 month to less than 2 years; maltol and maltol glucuronide in urine from both PK days in children aged 1 month to less than 2 years. Study design: The study comprised the following stages: 1. Screening: To determine subject eligibility for the study (within 21 days prior to randomisation for each subject). 2. Pre-assignment PK phase: only applicable for subjects aged 1 month to less than 2 years. Up to 28 days from Screening. All eligible subjects aged 1 month to less than 2 years entered a Pre-assignment phase, 1-day Pharmacokinetic assessment day following a single oral dose of ferric trimaltol suspension composition. After a baseline urine sample was collected, subjects took a single dose of 0.1 ml / kg ferric trimaltol suspension composition under supervision and then further urine samples from three timepoints up to 12 hours. The PK samples were analysed and if evidence of metabolism and elimination of maltol was shown, these subjects entered the treatment phase and were assigned to the ferric maltol arm. Randomised treatment: 12 weeks open label treatment. 3. Assigned treatment phase: 12 weeks open label treatment for ferric maltol children aged 1 month to less than 2 years. Once the PK samples collected from the pre-assignment phase were analysed for subjects aged 1 month to less than 2 years and confirmed they were enrolled in the randomisation phase, they were assigned to receive ferric maltol oral suspension and start the 0.1 ml / kg / dose, BID (maximum 2.5 ml BID) dose on Visit 2 and continue for 7-10 days. On Visit 3 (PK Day 2), following baseline pre-dose blood sample and urine sample, subjects took a single dose of 0.1 ml / kg ferric maltol liquid suspension composition under supervision. Further three PK blood and urine samples were collected up to 12 hours post dose. Subjects continued until week 12. 4. End of study: Week 12 visit. 5. Post-treatment safety follow-up: 10-14 days following study completion of the treatment period or premature discontinuation. Inclusion Criteria: 1. Age >1 month and <2 years at the time of informed consent. 2. Subjects must have iron deficiency anaemia defined by the following criteria, as measured by the central laboratory at the screening visit: Haemoglobin thresholds define anaemia by age: Children (1 m - <2 yrs) <11.0 g / dI and Ferritin thresholds define anaemia by: ferritin <30 pg / L, or ferritin <50 p.g / L with transferrin saturation (TSAT) <20 %. Exclusion Criteria: A subject who meets any of the following criteria is not eligible for participation in the study. 1. Subject with anaemia due to any cause other than iron deficiency, including, but not limited to untreated or untreatable severe malabsorption syndrome. 2. Subjects who have received prior to Screening: within 28 days intramuscular or intravenous (IV) injection or administration of depot iron preparation; within 7 days single agent iron preparations and during the study; within 12 weeks of blood transfusion or is scheduled to have blood transfusion during the study period; within 28 days erythropoiesis stimulating agents and during the study period; within 14 days COVID-19 vaccination. 3. Subjects with vitamin B12 or folic acid deficiency as determined by the central laboratory screening results. Subjects may start vitamin B12 or folate replacement and rescreen after at least 2 weeks. 4. Has concomitant disease that would significantly compromise iron absorption or absorbed iron utilization such as swallowing disorders and / or extensive small bowel resection. 5. History of active peptic ulcer. 6. Has chronic renal disease (eGFR <60 mL / min / m2), as assessed at Screening based on serum creatinine. 7. Known hypersensitivity or allergy to either the active substance or excipients of ferric maltol. 8. Has a known contraindication for treatment with iron preparations, e.g. haemochromatosis, chronic haemolytic disease, sideroblastic anaemia, thalassemia, or lead intoxication induced anaemia. 9. Impaired liver function as indicated by alanine aminotransferase (ALT) or aspartate transaminase (AST)>2.0 times upper normal limit as measured at the Screening visit. 10. Active acute inflammatory disease, including IBD flare or disease exacerbation, which in the opinion of the Investigator, is clinically significant. 11. Active chronic or acute infectious diseases requiring antibiotic treatment. 12. Concomitant medical conditions with extensive active bleeding. 13. Scheduled or expected hospitalisation and / or surgery during the course of the study. 14. Participation in any other interventional clinical study within 28 days prior to Screening. 15. Diagnosed to be COVID-19 positive by (SARS-CoV-2-RT-PCR positive) within 28 days prior to screening. 16. Cardiovascular, liver, renal, hematologic, psychiatric, neurologic, gastrointestinal, immunologic, endocrine, metabolic, respiratory or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject and / or objectives of the study drug or severely limit the lifespan of the subject. 17. Any other unspecified reason that, in the opinion of the Investigator make the subject unsuitable for enrolment. Concomitant Medication: Not Permitted: 1. Treatment with other single agent oral iron preparations (prescription and non-prescription) within 7 days prior to screening and throughout the study period. 2. Treatment with parenteral iron preparations within 28 days prior to screening and throughout the study period. 3. Blood transfusions within 12 weeks before screening and during the study. 4. Erythropoiesis stimulating agents within 28 days before screening and during the study. Permitted: 1. Immunosuppressants. 2. Vitamin B12 and folic acid supplements / replacement are allowed during the study. 3. Over the Counter (OTC) oral supplements / multivitamin type preparations (including those that contain iron) may be taken, however subjects should keep the same dose during the study. 4. All other concomitant medications must remain stable from Screening and throughout the study. Discontinuation Criteria: Subjects may be discontinued prematurely during the study for the following reasons: 1. Withdrawal of informed consent. 2. >1 g / dl Hb drop from baseline. 3. Unwillingness or inability to comply with protocol requirements. 4. Use of prohibited concomitant medications. 5. Serious adverse events that are judged by the Investigator to be related to study treatment. 6. Blood transfusions for any cause during the study treatment period. 7. Use of any other single agent prescribed iron medications. Investigational Medicinal Product: Ferric trimaltol oral liquid suspension composition: oral liquid suspension composition containing 30 mg elemental ferric iron, in the form of 231.5 mg ferric trimaltol in 5 ml liquid suspension composition (6 mg ferric iron equivalent per ml). More particularly, the liquid suspension composition consists of: 4.69 % w / v ferric trimaltol; 30.60 % w / v viscosity modifier; 0.50 % w / v surfactant; 0.20 % w / v preservative; 5.00 % w / v suspending agent; 0.30 % w / v flavouring agent; 0.20 % w / v sweetening agent; 2.61 % w / v pH regulator; and q.s. diluent. Ferric trimaltol oral liquid suspension composition was taken every morning and evening at least 30 minutes after a meal. Statistical Methods: Safety and gastrointestinal tolerability are presented via summaries of treatment emergent adverse events (TEAEs), treatment emergent serious AEs (TESAEs) and treatment-emergent AEs (TEAEs) leading to premature discontinuation of study drug. Efficacy of ferric maltol was assessed via the change in Hb concentration from baseline to week 12. For the PK analysis, all analytes in serum were summarised per PK day, for children aged 1 month to less than 2 years receiving ferric maltol. In addition, all analytes in urine were summarised per PK day, for children aged 1 month to less than 2 years. Analytical Methods: Hemoglobin (Hb) in serum was determined using spectrophotometry being calculated and reported in the automated blood count (CBC) performed on a Beckman Coulter UniCel DxH 800 / 900 hematology analyzer. Maltol and maltol glucuronide in plasma and urine were measured using a HPLC method (LC-MS) with reference standards. Results: Four infants were enrolled into the study of which 3 received study drug. For the 3 treated infants: mean age 11.7 months, range 11 months to 12 months. 2 females and 1 male, 1 Asian, 1 white 1 'other' race. The change in Hb from baseline at week 12 (Day 84) was 17.7 g / l (SD = 13.61)(N=3), which is highly clinically significant. The minimum rise was 7g / l and maximum rise was 33g / l. Two subjects reported a treatment emergent adverse event (AE). None of these AEs were considered drug-related. There was one serious AE (wheezing) reported which was not considered to be drug related. There were no discontinuations due to AEs in the infants and all 3 subjects who started treatment finished the 12 week study. This is a favorable safety profile for an oral iron product in any pediatric or adult age group. Maltol was rapidly metabolized to maltol glucuronide in infants. Maltol was not detectable in the plasma at 1 to 2 hours after administration whereas maltol glucuronide plasma concentrations peaked 1 to 2 hours after administration and had declined to negligible levels by 3 to 4 hours after administration. Negligible amounts of maltol were detected in the urine after administration compared to maltol glucuronide. Maltol glucuronide levels peaked at 0.5 to 3 hours after administration, returning to negligible levels after 7-12 hours. Conclusions: The maltol component of ferric trimaltol is rapidly metabolized and excreted in infants aged 11 months and above and does not accumulate. Ferric maltol was well tolerated in infants and treatment for 12 weeks resulted in a clinically significant rise in Hb compared to baseline in all subjects. The ferric trimaltol liquid suspension composition is therefore effective in the treatment of iron deficiency anaemia (IDA) in infants.

Claims

1. Ferric trimaltol for use in treating or preventing iron deficiency in a human patient with or without anaemia, wherein the ferric trimaltol is administered orally, wherein the patient is aged 1 month to less than 2 years old, preferably 1-23, 3-23, 6-23, 9-23,11-23, 9-21, 9-18,10-18, or 11-18 months old.

2. Ferric trimaltol for use in treating or preventing iron deficiency according to claim 1, wherein the ferric trimaltol is administered in the form of a liquid composition or liquid suspension composition.

3. Ferric trimaltol for use in treating or preventing iron deficiency according to claim 1 or claim 2, wherein iron deficiency is iron deficiency with or without anaemia resulting from one or more of the group consisting of nutritional deficiency, kidney disease, coeliac disease and other malabsorption disorders, inflammatory bowel disease (IBD) and cancer.

4. Ferric trimaltol for use in treating or preventing iron deficiency according to claim 3, wherein the inflammatory bowel disease is Crohn's disease.

5. Ferric trimaltol for use in treating or preventing iron deficiency according to claim 4, wherein the Crohn's disease is not active.

6. Ferric trimaltol for use in treating or preventing iron deficiency according to claim 5, wherein the human patient has a Crohn's Disease Activity Index of <220.

7. Ferric trimaltol for use in treating or preventing iron deficiency according to claim 3, wherein the inflammatory bowel disease is ulcerative colitis.

8. Ferric trimaltol for use in treating or preventing iron deficiency according to claim 7, wherein the ulcerative colitis is not active.

9. Ferric trimaltol for use in treating or preventing iron deficiency according to claim 8, wherein the human patient has a Simple Clinical Colitis Activity Index (SCCAI) value of <4.

10. Ferric trimaltol for use in treating or preventing iron deficiency according to any one of the preceding claims, wherein the ferric trimaltol is administered in the form of a 0.06-1.2 or 0.3-0.9 mg / kg body weight ferric iron equivalent dose twice a day.

11. Ferric trimaltol for use in treating or preventing iron deficiency according to claim 10, wherein the ferric trimaltol is administered once in the morning and once during the evening.

12. Ferric trimaltol for use in treating or preventing iron deficiency according to any one of the preceding claims, wherein the ferric trimaltol is administered for at least 24, 20, 16, 15, 14, 13, 12, 8, 4 weeks.

13. Ferric trimaltol for use in treating or preventing iron deficiency according to claim 12, wherein the ferric trimaltol is subsequently administered, optionally indefinitely as a maintenance dose, administered in the form of a 0.06-1.2 or 0.3-0.9 mg / kg body weight ferric iron equivalent dose once or twice a day.

14. Ferric trimaltol for use in treating or preventing iron deficiency according to any one of the preceding claims, wherein the ferric trimaltol is administered on an empty stomach.

15. Ferric trimaltol for use in treating or preventing iron deficiency according to any one of claims 1 to 13, wherein the ferric trimaltol is administered on a full or partially full stomach.