Iron Deficiency, Anaemia in Children, Iron-Deficiency
Conditions
Brief summary
The study has been designed to establish the pharmacokinetics (PK) and iron uptake of Ferric Maltol in children and adolescents aged 10-17 years using two (2) lower dose strengths in comparison to the EU-approved 30mg BID dose in adults with IDA in IBD.
Detailed description
Phase I, open label, randomized, repeat dose, multicentre, pharmacokinetic study to assess the Safety and Tolerability of Ferric Maltol in 3 different dosages. 36 eligible patients will be randomized in a 1:1:1 ratio to one of the following 3 dosages for 9 days BID and a single dose on Day 10: * 30mg ferric maltol capsules * 16.6 mg ferric maltol capsules * 7.8 mg ferric maltol capsules Subject participation in the study will consist of 3 stages: Screening: up to 14 days Treatment period: 10 days treatment period with 2 visits on Day 1 and Day 10 for PK blood sampling. Patients will be randomly allocated to one of the three Ferric Maltol dose groups according to centralized treatment allocation scheme. Post-treatment Safety Follow-up:3-10 days following completion of the treatment period or premature discontinuation of study medication
Interventions
DRUGFerric Maltol
To assess the pharmacokinetics and iron uptake of Ferric Maltol through measurement of serum iron, transferrin saturation (TSAT) and plasma concentrations of maltol and maltol glucuronide.
Sponsors
Medpace, Inc.
Shield Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Subjects will be randomized in a 1:1:1 ratio and stratified by co-variates for age and sex. This will ensure that a minimum of 25% of each gender and at least 3 children per age group are enrolled in each Ferric Maltol dose group.
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Ability to understand the information given in the Independent Ethics Committee (IEC) approved Information Sheet and Consent form. The parent or guardian of the study subject must sign and date the informed consent and authorisation to use protected health information (PHI) in accordance with national and local subject privacy regulations prior to any study mandated procedure. The study participant will be asked to provide their assent to participate in the study using the IEC approved Assent form. 2. Willing and able to comply with study requirements. 3. Age ≥10 to ≤17 years at the time of informed consent and throughout duration of the study. 4. A current diagnosis of iron deficiency (with or without anaemia); iron deficiency defined by ferritin \<30 µg/L, or ferritin \<50 µg/L with transferrin saturation (TSAT) \<20%, as measured by the central laboratory at the Screening visit (subjects with or without anaemia may be enrolled providing Hb is ≥8.5 g/dL as measured at the Screening visit). 5. Where appropriate, female subjects of childbearing potential must agree to use a reliable method of contraception until study completion and for at least 4 weeks following their final study visit. Reliable contraception is defined as a method which results in a low failure rate, i.e., less than 1% per year when used consistently and correctly, such as implants, injectables, some intrauterine contraceptive devices (IUDs), complete sexual abstinence, a vasectomized partner and oral contraceptive medications.
Exclusion criteria
1. Has untreated or untreatable severe malabsorption syndrome e.g., untreated coeliac disease 2. Has received within 28 days prior to Screening intramuscular or intravenous (IV) injection or administration of depot iron preparation. 3. Has received oral iron supplementation within 7 days prior to Screening 4. Has received blood transfusion within 12 weeks prior to Screening or is scheduled to have blood transfusion or donations during the study period. 5. Has concomitant disease that would significantly compromise iron absorption or absorbed iron utilisation such as swallowing disorders and/or extensive small bowel resection. 6. Has chronic renal disease (eGFR \<30mL/min), as assessed at Screening based on serum creatinine. 7. Known hypersensitivity or allergy to either the active substance or excipients of Ferric Maltol capsules. 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. Pregnant or breast feeding. 13. Concomitant medical conditions with extensive active bleeding, other than menstrual cycles; subjects who suffer from menorrhagia may be included at the Investigator's discretion. 14. Scheduled or expected hospitalisation and/or surgery during the course of the study 15. Participation in any other interventional clinical study 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 or the Sponsor make the subject unsuitable for enrolment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Systemic Clearance (CL/F) of Maltol Glucuronide on Day 10 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h | Descriptive statistics and population PK analysis of plasma maltol glucuronide CL/F from PK samples collected on Day 10. |
| Transferrin Saturation (%) Day 1, Maximum Response (%) | Measured after first dose of Ferric Maltol on Day 1 (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Transferrin Saturation (TSAT%) Day 1, maximum response (%) |
| Transferrin Saturation Day 1, Time to Maximum Response Tmax | Measured after first dose of Ferric Maltol on Day 1. (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Transferrin Saturation (TSAT%) Day 1, time to maximum response Tmax (h). Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Transferrin Saturation (%) Day 10, Maximum Response (%) | Measured after last dose of Ferric Maltol on Day 10. (0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Transferrin Saturation (TSAT%) Day 10, maximum response (%). Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Transferrin Saturation Day 10, Time to Maximum Response Tmax | Measured after first dose of Ferric Maltol on Day 10. (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). | Transferrin Saturation (TSAT%) Day 1, time to maximum response Tmax (h). Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| AUC0-inf Day 1 for Maltol Glucuronide | Measured after first dose of Ferric Maltol on Day 1 (0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | AUC0-inf for Maltol Glucuronide from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| AUC0-tau Day 10 for Maltol Glucuronide | Measured after last dose of Ferric Maltol on Day 10. (0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | AUC0-tau for Maltol Glucuronide from PK samples collected on Day 10. Area under the plasma concentration versus time curve from time 0 to tau. |
| Serum Iron Cmax Day 1 | Day 1 (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Maximum serum concentration of serum iron on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Serum Iron Cmax on Day 10 | Day 10 (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Maximum serum concentration of serum iron on Day 10. |
| Plasma Maltol Glucuronide Cthrough D10/Day1 | Day 10 (0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Minimum concentration between dose time and dose time+TAU |
| Apparent Systemic Clearance (CL/F) of Transferrin Saturation (TSAT) on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h | Descriptive statistics and population PK analysis of serum TSAT CL/F from PK samples collected on Day 1 |
| Apparent Systemic Clearance (CL/F) of Transferrin Saturation (TSAT) on Day 10 | Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of serum TSAT CL/F from PK samples collected on Day 10 |
| Apparent Systemic Clearance (CL/F) of Maltol Glucuronide on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h | Descriptive statistics and population PK analysis of plasma maltol glucuronide CL/F from PK samples collected on Day 1. |
| Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of maltol glucuronide Cmax from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 10 | Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of maltol glucuronide Cmax from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Cthrough for Maltol Glucuronide Day 10 | Day 10 pre-dose to last (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Change from pre-dose to last PK samples collected on Day 10 for maltol glucuronide.Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Area Under The Curve [AUC] of Maltol Glucuronide on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of maltol glucuronide AUC from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Area Under The Curve [AUC] of Maltol Glucuronide on Day 10 | Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of maltol AUC from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Average Plasma Concentration [Cave(0-6h)] of Maltol Glucuronide on Day 10 | Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of maltol glucuronide Cave(0-6h) from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Time of Maximum Plasma Concentration [Tmax] of Maltol Glucuronide on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of maltol glucuronide Tmax from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Time of Maximum Plasma Concentration [Tmax] of Maltol Glucuronide on Day 10 | Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of maltol glucuronide Tmax from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Half Life [t1/2] of Maltol Glucuronide on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of maltol glucuronide t1/2 from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Ratio of Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 10/Day 1 | Day 1 and Day 10, pre-dose and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics of ratio maltol glucuronide Cmax Day 10/Day 10 from PK samples collected on Day 1 and Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Ratio of Area Under The Curve [AUC] of Maltol Glucuronide on Day 10/Day 1 | Day 1 and Day 10, pre-dose and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics of ratio maltol glucuronide AUC Day 10/Day 10 from PK samples collected on Day 1 and Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Average Serum Concentration [Cave(0-6h)] of Iron on Day 10 | Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of iron Cave(0-6h) from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Change From Pre-Dose (Ctrough) to Maximum Post-Dose (Cmax) in Serum Iron on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of change in serum iron \[Ctrough to Cmax\] from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Change From Pre-Dose (Ctrough) to Maximum Post-Dose (Cmax) in Serum Iron on Day 10 | Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of change in serum iron \[Ctrough to Cmax\] from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Serum Iron on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of pre-dose adjusted incremental AUC(0-6h) of serum iron from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Serum Iron on Day 10 | Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of pre-dose adjusted incremental AUC(0-6h) of serum iron from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Transferrin Saturation (TSAT) on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of pre-dose adjusted incremental AUC(0-6h) of TSAT from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Transferrin Saturation (TSAT) on Day 10 | Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of pre-dose adjusted incremental AUC(0-6h) of TSAT from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Apparent Systemic Clearance (CL/F) of Iron on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of serum iron CL/F from PK samples collected on Day 1 |
| Apparent Systemic Clearance (CL/F) of Iron on Day 10 | Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of serum iron CL/F from PK samples collected on Day 10 |
| Apparent Volume of Distribution (V/F) of Iron on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of iron V/F from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10. |
| Apparent Volume of Distribution (V/F) of Transferrin Saturation (TSAT) on Day 1 | Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of TSAT V/F from PK samples collected on Day 1 |
| Apparent Volume of Distribution (V/F) of Transferrin Saturation (TSAT) on Day 10 | Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Descriptive statistics and population PK analysis of TSAT V/F from PK samples collected on Day 10 |
| Ratio Auc(0-6) Maltol Glucuronide Day 10/Day 1 | Day 1 to Day 10 (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Ratio AUC0-6h measured after last dose of Ferric Maltol on Day 10 vs first dose Day 1. |
| Serum Iron - RAUC(0-6h) D10/D1 | Measured after first and last dose of Ferric Maltol on Day 1 & Day 10 (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h) | Serum Iron - RAUC(0-6h) Day 10/Day 1 |
| Transferrin Saturation (%) Day 1, Baseline | Measured after first dose of Ferric Maltol on Day 1 (0h) | Transferrin Saturation (TSAT%) Day 1, baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| UIBC - Change From Day 1 to Day 10, Predose | Pre-dose on Day 1 to Day 10 (0h each day) | Change calculated as difference in values measured at Day 1, predose and on Day 10, predose |
| Negative and Positive NTBI Tests on Day 1 | Day 1 (0h) | Negative and Positive Non-Transferrin Bound Iron \[NTBI\] tests on Day 1, predose |
| Transferrin - Change From Baseline to Day 10, Predose | Day 1 pre-dose to Day 10 pre-dose (0h on each day) | Change calculated as difference in values measured at Day 1, predose (Baseline) and on Day 10, predose |
| Ferritin - Change From Baseline to Day 10, Predose | Pre-dose on Day 1 to Day 10 (0h) | Change calculated as difference in values measured at Day 1, predose (Baseline) and on Day 10, predose. |
| Change From Baseline to Day 10 in Haemoglobin Concentration | Screening and Day 10 (1-4 hours post-dose) | Change calculated as difference in values measured at Screening (Baseline) and on Day 10 |
| Change From Baseline to Day 10 in Absolute Reticulocyte Count | Change calculated as difference in values measured at Screening (Baseline) and on Day 10. | Change from Baseline to Day 10 in Absolute Reticulocyte Count collected from PK samples |
| Treatment-emergent Adverse Events (AEs) Leading to Premature Discontinuation of Study Drug/PK Assessments | From first dose of Ferric Maltol on Day 1 through study completion, on average 4 weeks | Descriptive summary of incidence and causal relationship of treatment-emergent adverse events leading to discontinuation of study drug/PK assessments according to MedDRA preferred term (PT) and system organ class (SOC) |
| Changes in 12-lead ECG Parameters From Screening to Day 10 | Screening and Day 10 (1-4 hours post-dose) | Overall clinical interpretation of routine ECG parameters from Screening to Day 10 |
| Concomitant Medications | Screening, Day 1, Day 10 and Post-Study Follow-up visit, on average 4 weeks | Number of subjects with concomitant medications Taken by \>5% of Subjects |
| Negative and Positive NTBI Tests on Day 10, Predose | Day 10 | Negative and Positive Non-Transferrin Bound Iron \[NTBI\] tests on Day 10, predose |
| Treatment-emergent Serious Adverse Event (TESAE) | From first dose of ferric maltol Day 1 through study completions, on average 4 weeks | Descriptive summary of TESAE according to MedDRA preferred Term |
| Total Iron Binding Capacity - Change From Day 1 to Day 10, Predose | Predose from Day 1 to Day 10 (0h on each day) | Change calculated as difference in values measured at Day 1, predose and on Day 10, predose |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 7.8 mg Ferric Maltol 12 subjects will receive 7.8 mg Ferric Maltol twice daily for 9 days (Days 1-9) plus a final 7.8 mg dose on the morning of Day 10. PK study Day 1 & Day 10.
Ferric Maltol: To assess the pharmacokinetics and iron uptake of Ferric Maltol through measurement of serum iron, transferrin saturation (TSAT) and plasma concentrations of maltol and maltol glucuronide. | 12 |
| 16.6 mg Ferric Maltol 13 subjects will receive 16.6 mg Ferric Maltol twice daily for 9 days (Days 1-9) plus a final 16.6 mg dose on the morning of Day 10. PK study Day 1 & Day 10.
Ferric Maltol: To assess the pharmacokinetics and iron uptake of Ferric Maltol through measurement of serum iron, transferrin saturation (TSAT) and plasma concentrations of maltol and maltol glucuronide. | 13 |
| 30 mg Ferric Maltol 12 subjects will receive 30 mg Ferric Maltol twice daily for 9 days (Days 1-9) plus a final 30 mg dose on the morning of Day 10. PK study Day 1 & Day 10.
Ferric Maltol: To assess the pharmacokinetics and iron uptake of Ferric Maltol through measurement of serum iron, transferrin saturation (TSAT) and plasma concentrations of maltol and maltol glucuronide. | 12 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 7.8 mg Ferric Maltol | 16.6 mg Ferric Maltol | 30 mg Ferric Maltol | Total |
|---|---|---|---|---|
| Age, Continuous | 14.1 years STANDARD_DEVIATION 1.56 | 13.7 years STANDARD_DEVIATION 1.8 | 14.2 years STANDARD_DEVIATION 2.12 | 14.0 years STANDARD_DEVIATION 1.8 |
| Age, Customized 10-14 | 8 Participants | 7 Participants | 8 Participants | 23 Participants |
| Age, Customized 15-17 | 4 Participants | 6 Participants | 4 Participants | 14 Participants |
| BMI | 22.695 kg/m^2 STANDARD_DEVIATION 7.4067 | 24.265 kg/m^2 STANDARD_DEVIATION 7.7647 | 19.760 kg/m^2 STANDARD_DEVIATION 2.7049 | 22.182 kg/m^2 STANDARD_DEVIATION 6.4355 |
| Ferritin | 16.2 μg/L STANDARD_DEVIATION 7.18 | 18.8 μg/L STANDARD_DEVIATION 8.29 | 13.8 μg/L STANDARD_DEVIATION 8.34 | 16.3 μg/L STANDARD_DEVIATION 8.02 |
| Haemoglobin | 12.27 g/dL STANDARD_DEVIATION 0.856 | 12.75 g/dL STANDARD_DEVIATION 1.067 | 12.37 g/dL STANDARD_DEVIATION 1.418 | 12.47 g/dL STANDARD_DEVIATION 1.124 |
| Height | 1.590 m STANDARD_DEVIATION 0.0641 | 1.601 m STANDARD_DEVIATION 0.855 | 1.618 m STANDARD_DEVIATION 0.0914 | 1.603 m STANDARD_DEVIATION 0.0799 |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 11 Participants | 13 Participants | 11 Participants | 35 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 4 Participants | 13 Participants |
| Weight | 57.83 kg STANDARD_DEVIATION 20.961 | 62.77 kg STANDARD_DEVIATION 23.33 | 52.07 kg STANDARD_DEVIATION 9.661 | 57.41 kg STANDARD_DEVIATION 18.758 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 7 / 12 | 7 / 13 | 7 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 | 0 / 12 |
Outcome results
Primary
Apparent Systemic Clearance (CL/F) of Iron on Day 1
Descriptive statistics and population PK analysis of serum iron CL/F from PK samples collected on Day 1
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Apparent Systemic Clearance (CL/F) of Iron on Day 1 | 1.321 L/h | Standard Deviation 0.6945 |
| 16.6 mg Ferric Maltol | Apparent Systemic Clearance (CL/F) of Iron on Day 1 | 0.654 L/h | Standard Deviation 0.2441 |
| 7.8 mg Ferric Maltol | Apparent Systemic Clearance (CL/F) of Iron on Day 1 | 0.324 L/h | Standard Deviation 0.1517 |
Primary
Apparent Systemic Clearance (CL/F) of Iron on Day 10
Descriptive statistics and population PK analysis of serum iron CL/F from PK samples collected on Day 10
Time frame: Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Apparent Systemic Clearance (CL/F) of Iron on Day 10 | 3.264 L/h | Standard Deviation 2.2297 |
| 16.6 mg Ferric Maltol | Apparent Systemic Clearance (CL/F) of Iron on Day 10 | 1.757 L/h | Standard Deviation 0.6673 |
| 7.8 mg Ferric Maltol | Apparent Systemic Clearance (CL/F) of Iron on Day 10 | 0.808 L/h | Standard Deviation 0.3089 |
Primary
Apparent Systemic Clearance (CL/F) of Maltol Glucuronide on Day 1
Descriptive statistics and population PK analysis of plasma maltol glucuronide CL/F from PK samples collected on Day 1.
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h
Population: The dose of maltol glucuronide was not calculable using non-compartmental analysis.
Primary
Apparent Systemic Clearance (CL/F) of Maltol Glucuronide on Day 10
Descriptive statistics and population PK analysis of plasma maltol glucuronide CL/F from PK samples collected on Day 10.
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h
Population: The dose of maltol glucuronide was not calculable using non-compartmental analysis.
Primary
Apparent Systemic Clearance (CL/F) of Transferrin Saturation (TSAT) on Day 1
Descriptive statistics and population PK analysis of serum TSAT CL/F from PK samples collected on Day 1
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h
Population: As PPD analysis was performed the CL/F could not be estimated.
Primary
Apparent Systemic Clearance (CL/F) of Transferrin Saturation (TSAT) on Day 10
Descriptive statistics and population PK analysis of serum TSAT CL/F from PK samples collected on Day 10
Time frame: Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: As PPD analysis was performed, the V/F could not be estimated.
Primary
Apparent Volume of Distribution (V/F) of Iron on Day 1
Descriptive statistics and population PK analysis of iron V/F from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Apparent Volume of Distribution (V/F) of Iron on Day 1 | 22.114 L | Standard Deviation 7.2315 |
| 16.6 mg Ferric Maltol | Apparent Volume of Distribution (V/F) of Iron on Day 1 | 14.244 L | Standard Deviation 4.8083 |
| 7.8 mg Ferric Maltol | Apparent Volume of Distribution (V/F) of Iron on Day 1 | 10.462 L | Standard Deviation 3.1033 |
Primary
Apparent Volume of Distribution (V/F) of Transferrin Saturation (TSAT) on Day 1
Descriptive statistics and population PK analysis of TSAT V/F from PK samples collected on Day 1
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: As PPD analysis was performed, the V/F could not be estimated.
Primary
Apparent Volume of Distribution (V/F) of Transferrin Saturation (TSAT) on Day 10
Descriptive statistics and population PK analysis of TSAT V/F from PK samples collected on Day 10
Time frame: Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: As PPD analysis was performed, the V/F could not be estimated.
Primary
Area Under The Curve [AUC] of Maltol Glucuronide on Day 1
Descriptive statistics and population PK analysis of maltol glucuronide AUC from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Area Under The Curve [AUC] of Maltol Glucuronide on Day 1 | 11.090 h*mg/L | Standard Deviation 3.9033 |
| 16.6 mg Ferric Maltol | Area Under The Curve [AUC] of Maltol Glucuronide on Day 1 | 5.613 h*mg/L | Standard Deviation 0.7589 |
| 7.8 mg Ferric Maltol | Area Under The Curve [AUC] of Maltol Glucuronide on Day 1 | 2.585 h*mg/L | Standard Deviation 0.0968 |
Primary
Area Under The Curve [AUC] of Maltol Glucuronide on Day 10
Descriptive statistics and population PK analysis of maltol AUC from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Area Under The Curve [AUC] of Maltol Glucuronide on Day 10 | 20.511 h*mg/L | Standard Deviation 1.7997 |
| 16.6 mg Ferric Maltol | Area Under The Curve [AUC] of Maltol Glucuronide on Day 10 | 10.518 h*mg/L | Standard Deviation 0.5277 |
| 7.8 mg Ferric Maltol | Area Under The Curve [AUC] of Maltol Glucuronide on Day 10 | 5.016 h*mg/L | Standard Deviation 0.1133 |
Primary
AUC0-inf Day 1 for Maltol Glucuronide
AUC0-inf for Maltol Glucuronide from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Measured after first dose of Ferric Maltol on Day 1 (0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | AUC0-inf Day 1 for Maltol Glucuronide | 8.590 h.mg/L | Standard Deviation 0.2025 |
| 16.6 mg Ferric Maltol | AUC0-inf Day 1 for Maltol Glucuronide | 17.862 h.mg/L | Standard Deviation 0.9328 |
| 7.8 mg Ferric Maltol | AUC0-inf Day 1 for Maltol Glucuronide | 34.372 h.mg/L | Standard Deviation 4.5052 |
Primary
AUC0-tau Day 10 for Maltol Glucuronide
AUC0-tau for Maltol Glucuronide from PK samples collected on Day 10. Area under the plasma concentration versus time curve from time 0 to tau.
Time frame: Measured after last dose of Ferric Maltol on Day 10. (0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | AUC0-tau Day 10 for Maltol Glucuronide | 8.59 h mg/L | Standard Deviation 0.2024 |
| 16.6 mg Ferric Maltol | AUC0-tau Day 10 for Maltol Glucuronide | 17.862 h mg/L | Standard Deviation 0.9327 |
| 7.8 mg Ferric Maltol | AUC0-tau Day 10 for Maltol Glucuronide | 34.368 h mg/L | Standard Deviation 4.4981 |
Primary
Average Plasma Concentration [Cave(0-6h)] of Maltol Glucuronide on Day 10
Descriptive statistics and population PK analysis of maltol glucuronide Cave(0-6h) from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Average Plasma Concentration [Cave(0-6h)] of Maltol Glucuronide on Day 10 | 3.4186 mg/L | Standard Deviation 0.29995 |
| 16.6 mg Ferric Maltol | Average Plasma Concentration [Cave(0-6h)] of Maltol Glucuronide on Day 10 | 1.7531 mg/L | Standard Deviation 0.08795 |
| 7.8 mg Ferric Maltol | Average Plasma Concentration [Cave(0-6h)] of Maltol Glucuronide on Day 10 | 0.8360 mg/L | Standard Deviation 0.01889 |
Primary
Average Serum Concentration [Cave(0-6h)] of Iron on Day 10
Descriptive statistics and population PK analysis of iron Cave(0-6h) from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Average Serum Concentration [Cave(0-6h)] of Iron on Day 10 | 1.1667 mg/L | Standard Deviation 0.6142 |
| 16.6 mg Ferric Maltol | Average Serum Concentration [Cave(0-6h)] of Iron on Day 10 | 0.9557 mg/L | Standard Deviation 0.29645 |
| 7.8 mg Ferric Maltol | Average Serum Concentration [Cave(0-6h)] of Iron on Day 10 | 0.9748 mg/L | Standard Deviation 0.39783 |
Primary
Change From Pre-Dose (Ctrough) to Maximum Post-Dose (Cmax) in Serum Iron on Day 1
Descriptive statistics and population PK analysis of change in serum iron \[Ctrough to Cmax\] from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Change From Pre-Dose (Ctrough) to Maximum Post-Dose (Cmax) in Serum Iron on Day 1 | 0.6159 mg/L | Standard Deviation 0.3232 |
| 16.6 mg Ferric Maltol | Change From Pre-Dose (Ctrough) to Maximum Post-Dose (Cmax) in Serum Iron on Day 1 | 0.4102 mg/L | Standard Deviation 0.22144 |
| 7.8 mg Ferric Maltol | Change From Pre-Dose (Ctrough) to Maximum Post-Dose (Cmax) in Serum Iron on Day 1 | 0.21715 mg/L | Standard Deviation 0.11873 |
Primary
Change From Pre-Dose (Ctrough) to Maximum Post-Dose (Cmax) in Serum Iron on Day 10
Descriptive statistics and population PK analysis of change in serum iron \[Ctrough to Cmax\] from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Change From Pre-Dose (Ctrough) to Maximum Post-Dose (Cmax) in Serum Iron on Day 10 | 0.5486 mg/L | Standard Deviation 0.32367 |
| 16.6 mg Ferric Maltol | Change From Pre-Dose (Ctrough) to Maximum Post-Dose (Cmax) in Serum Iron on Day 10 | 0.3625 mg/L | Standard Deviation 0.15333 |
| 7.8 mg Ferric Maltol | Change From Pre-Dose (Ctrough) to Maximum Post-Dose (Cmax) in Serum Iron on Day 10 | 0.2251 mg/L | Standard Deviation 0.08362 |
Primary
Cthrough for Maltol Glucuronide Day 10
Change from pre-dose to last PK samples collected on Day 10 for maltol glucuronide.Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 10 pre-dose to last (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: ITT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Cthrough for Maltol Glucuronide Day 10 | 0.4804 mg/L | Standard Deviation 0.01639 |
| 16.6 mg Ferric Maltol | Cthrough for Maltol Glucuronide Day 10 | 0.9762 mg/L | Standard Deviation 0.10586 |
| 7.8 mg Ferric Maltol | Cthrough for Maltol Glucuronide Day 10 | 1.8496 mg/L | Standard Deviation 0.67761 |
Primary
Half Life [t1/2] of Maltol Glucuronide on Day 1
Descriptive statistics and population PK analysis of maltol glucuronide t1/2 from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Half Life [t1/2] of Maltol Glucuronide on Day 1 | 11.384 h | Standard Deviation 5.4738 |
| 16.6 mg Ferric Maltol | Half Life [t1/2] of Maltol Glucuronide on Day 1 | 10.447 h | Standard Deviation 1.8503 |
| 7.8 mg Ferric Maltol | Half Life [t1/2] of Maltol Glucuronide on Day 1 | 10.806 h | Standard Deviation 0.4707 |
Primary
Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 1
Descriptive statistics and population PK analysis of maltol glucuronide Cmax from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 1 | 2.4518 mg/L | Standard Deviation 1.2959 |
| 16.6 mg Ferric Maltol | Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 1 | 1.1632 mg/L | Standard Deviation 0.18435 |
| 7.8 mg Ferric Maltol | Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 1 | 0.5299 mg/L | Standard Deviation 0.02245 |
Primary
Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 10
Descriptive statistics and population PK analysis of maltol glucuronide Cmax from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 10 | 4.2355 mg/L | Standard Deviation 0.7811 |
| 16.6 mg Ferric Maltol | Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 10 | 2.1028 mg/L | Standard Deviation 0.13342 |
| 7.8 mg Ferric Maltol | Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 10 | 0.9926 mg/L | Standard Deviation 0.02349 |
Primary
Plasma Maltol Glucuronide Cthrough D10/Day1
Minimum concentration between dose time and dose time+TAU
Time frame: Day 10 (0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Plasma Maltol Glucuronide Cthrough D10/Day1 | 0.4804 mg/L | Standard Deviation 0.0163 |
| 16.6 mg Ferric Maltol | Plasma Maltol Glucuronide Cthrough D10/Day1 | 0.9762 mg/L | Standard Deviation 0.105 |
| 7.8 mg Ferric Maltol | Plasma Maltol Glucuronide Cthrough D10/Day1 | 1.8496 mg/L | Standard Deviation 0.677 |
Primary
Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Serum Iron on Day 1
Descriptive statistics and population PK analysis of pre-dose adjusted incremental AUC(0-6h) of serum iron from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Serum Iron on Day 1 | 6.711 h*mg/L | Standard Deviation 2.5721 |
| 16.6 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Serum Iron on Day 1 | 5.963 h*mg/L | Standard Deviation 1.7793 |
| 7.8 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Serum Iron on Day 1 | 3.928 h*mg/L | Standard Deviation 1.1318 |
Primary
Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Serum Iron on Day 10
Descriptive statistics and population PK analysis of pre-dose adjusted incremental AUC(0-6h) of serum iron from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Serum Iron on Day 10 | 7.000 h*mg/L | Standard Deviation 3.6852 |
| 16.6 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Serum Iron on Day 10 | 5.734 h*mg/L | Standard Deviation 1.7787 |
| 7.8 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Serum Iron on Day 10 | 5.849 h*mg/L | Standard Deviation 2.387 |
Primary
Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Transferrin Saturation (TSAT) on Day 1
Descriptive statistics and population PK analysis of pre-dose adjusted incremental AUC(0-6h) of TSAT from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Transferrin Saturation (TSAT) on Day 1 | 179.47 h*% | Standard Deviation 60.259 |
| 16.6 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Transferrin Saturation (TSAT) on Day 1 | 159.21 h*% | Standard Deviation 50.723 |
| 7.8 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Transferrin Saturation (TSAT) on Day 1 | 104.50 h*% | Standard Deviation 41.009 |
Primary
Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Transferrin Saturation (TSAT) on Day 10
Descriptive statistics and population PK analysis of pre-dose adjusted incremental AUC(0-6h) of TSAT from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Transferrin Saturation (TSAT) on Day 10 | 180.14 h*% | Standard Deviation 76.193 |
| 16.6 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Transferrin Saturation (TSAT) on Day 10 | 149.40 h*% | Standard Deviation 37.799 |
| 7.8 mg Ferric Maltol | Pre-dose Adjusted Incremental Area Under the Curve [AUC(0-6h)] of Transferrin Saturation (TSAT) on Day 10 | 157.43 h*% | Standard Deviation 81.693 |
Primary
Ratio Auc(0-6) Maltol Glucuronide Day 10/Day 1
Ratio AUC0-6h measured after last dose of Ferric Maltol on Day 10 vs first dose Day 1.
Time frame: Day 1 to Day 10 (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Ratio Auc(0-6) Maltol Glucuronide Day 10/Day 1 | 1.942 Ratio | Standard Deviation 0.0582 |
| 16.6 mg Ferric Maltol | Ratio Auc(0-6) Maltol Glucuronide Day 10/Day 1 | 1.899 Ratio | Standard Deviation 0.2286 |
| 7.8 mg Ferric Maltol | Ratio Auc(0-6) Maltol Glucuronide Day 10/Day 1 | 2.030 Ratio | Standard Deviation 0.6695 |
Primary
Ratio of Area Under The Curve [AUC] of Maltol Glucuronide on Day 10/Day 1
Descriptive statistics of ratio maltol glucuronide AUC Day 10/Day 10 from PK samples collected on Day 1 and Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 1 and Day 10, pre-dose and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Ratio of Area Under The Curve [AUC] of Maltol Glucuronide on Day 10/Day 1 | 2.030 ratio | Standard Deviation 0.6695 |
| 16.6 mg Ferric Maltol | Ratio of Area Under The Curve [AUC] of Maltol Glucuronide on Day 10/Day 1 | 1.899 ratio | Standard Deviation 0.2286 |
| 7.8 mg Ferric Maltol | Ratio of Area Under The Curve [AUC] of Maltol Glucuronide on Day 10/Day 1 | 1.942 ratio | Standard Deviation 0.0582 |
Primary
Ratio of Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 10/Day 1
Descriptive statistics of ratio maltol glucuronide Cmax Day 10/Day 10 from PK samples collected on Day 1 and Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 1 and Day 10, pre-dose and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Ratio of Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 10/Day 1 | 1.956 ratio | Standard Deviation 0.621 |
| 16.6 mg Ferric Maltol | Ratio of Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 10/Day 1 | 1.836 ratio | Standard Deviation 0.2109 |
| 7.8 mg Ferric Maltol | Ratio of Maximum Plasma Concentration [Cmax] of Maltol Glucuronide on Day 10/Day 1 | 1.875 ratio | Standard Deviation 0.0537 |
Primary
Serum Iron Cmax Day 1
Maximum serum concentration of serum iron on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 1 (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Serum Iron Cmax Day 1 | 0.7030 mg/L | Standard Deviation 0.19765 |
| 16.6 mg Ferric Maltol | Serum Iron Cmax Day 1 | 1.681 mg/L | Standard Deviation 0.30405 |
| 7.8 mg Ferric Maltol | Serum Iron Cmax Day 1 | 1.2328 mg/L | Standard Deviation 0.47471 |
Primary
Serum Iron Cmax on Day 10
Maximum serum concentration of serum iron on Day 10.
Time frame: Day 10 (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Serum Iron Cmax on Day 10 | 1.0338 mg/L | Standard Deviation 0.4023 |
| 16.6 mg Ferric Maltol | Serum Iron Cmax on Day 10 | 1.0462 mg/L | Standard Deviation 0.3221 |
| 7.8 mg Ferric Maltol | Serum Iron Cmax on Day 10 | 1.3034 mg/L | Standard Deviation 0.6741 |
Primary
Serum Iron - RAUC(0-6h) D10/D1
Serum Iron - RAUC(0-6h) Day 10/Day 1
Time frame: Measured after first and last dose of Ferric Maltol on Day 1 & Day 10 (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Serum Iron - RAUC(0-6h) D10/D1 | 1.529 Ratio | Standard Deviation 1.4673 |
| 16.6 mg Ferric Maltol | Serum Iron - RAUC(0-6h) D10/D1 | 1.020 Ratio | Standard Deviation 0.317 |
| 7.8 mg Ferric Maltol | Serum Iron - RAUC(0-6h) D10/D1 | 1.038 Ratio | Standard Deviation 0.3973 |
Primary
Time of Maximum Plasma Concentration [Tmax] of Maltol Glucuronide on Day 1
Descriptive statistics and population PK analysis of maltol glucuronide Tmax from PK samples collected on Day 1. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 1 pre-first dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 30 mg Ferric Maltol | Time of Maximum Plasma Concentration [Tmax] of Maltol Glucuronide on Day 1 | 1.00 h |
| 16.6 mg Ferric Maltol | Time of Maximum Plasma Concentration [Tmax] of Maltol Glucuronide on Day 1 | 1.00 h |
| 7.8 mg Ferric Maltol | Time of Maximum Plasma Concentration [Tmax] of Maltol Glucuronide on Day 1 | 1.00 h |
Primary
Time of Maximum Plasma Concentration [Tmax] of Maltol Glucuronide on Day 10
Descriptive statistics and population PK analysis of maltol glucuronide Tmax from PK samples collected on Day 10. Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Day 10 pre-final dose of Ferric Maltol and up to 6 hours post-dose (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 30 mg Ferric Maltol | Time of Maximum Plasma Concentration [Tmax] of Maltol Glucuronide on Day 10 | 0.75 h |
| 16.6 mg Ferric Maltol | Time of Maximum Plasma Concentration [Tmax] of Maltol Glucuronide on Day 10 | 0.75 h |
| 7.8 mg Ferric Maltol | Time of Maximum Plasma Concentration [Tmax] of Maltol Glucuronide on Day 10 | 0.75 h |
Primary
Transferrin Saturation (%) Day 10, Maximum Response (%)
Transferrin Saturation (TSAT%) Day 10, maximum response (%). Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Measured after last dose of Ferric Maltol on Day 10. (0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Transferrin Saturation (%) Day 10, Maximum Response (%) | 27.779 percentage saturation | Standard Deviation 13.863 |
| 16.6 mg Ferric Maltol | Transferrin Saturation (%) Day 10, Maximum Response (%) | 27.214 percentage saturation | Standard Deviation 6.699 |
| 7.8 mg Ferric Maltol | Transferrin Saturation (%) Day 10, Maximum Response (%) | 33.524 percentage saturation | Standard Deviation 13.633 |
Primary
Transferrin Saturation Day 10, Time to Maximum Response Tmax
Transferrin Saturation (TSAT%) Day 1, time to maximum response Tmax (h). Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Measured after first dose of Ferric Maltol on Day 10. (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h).
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 30 mg Ferric Maltol | Transferrin Saturation Day 10, Time to Maximum Response Tmax | 3.00 hour |
| 16.6 mg Ferric Maltol | Transferrin Saturation Day 10, Time to Maximum Response Tmax | 3.00 hour |
| 7.8 mg Ferric Maltol | Transferrin Saturation Day 10, Time to Maximum Response Tmax | 3.00 hour |
Primary
Transferrin Saturation (%) Day 1, Baseline
Transferrin Saturation (TSAT%) Day 1, baseline
Time frame: Measured after first dose of Ferric Maltol on Day 1 (0h)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Transferrin Saturation (%) Day 1, Baseline | 11.5 percentage saturation | Standard Deviation 5.66 |
| 16.6 mg Ferric Maltol | Transferrin Saturation (%) Day 1, Baseline | 16.8 percentage saturation | Standard Deviation 9.25 |
| 7.8 mg Ferric Maltol | Transferrin Saturation (%) Day 1, Baseline | 15.8 percentage saturation | Standard Deviation 9.31 |
Primary
Transferrin Saturation (%) Day 1, Maximum Response (%)
Transferrin Saturation (TSAT%) Day 1, maximum response (%)
Time frame: Measured after first dose of Ferric Maltol on Day 1 (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Transferrin Saturation (%) Day 1, Maximum Response (%) | 18.68 percentage saturation | Standard Deviation 7.13 |
| 16.6 mg Ferric Maltol | Transferrin Saturation (%) Day 1, Maximum Response (%) | 28.261 percentage saturation | Standard Deviation 8.4784 |
| 7.8 mg Ferric Maltol | Transferrin Saturation (%) Day 1, Maximum Response (%) | 32.845 percentage saturation | Standard Deviation 10.5913 |
Primary
Transferrin Saturation Day 1, Time to Maximum Response Tmax
Transferrin Saturation (TSAT%) Day 1, time to maximum response Tmax (h). Each subject had 1 pre-dose (0h) and 2 post dose PK blood sampling between (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h). Subjects were assigned to PK blood sampling schedule. For each individual subject the PK blood sampling schedule was the same on Day 1 and Day 10.
Time frame: Measured after first dose of Ferric Maltol on Day 1. (0h, 0.5-1h, 1-2h, 2-3h, 3-4h, 4-6h)
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 30 mg Ferric Maltol | Transferrin Saturation Day 1, Time to Maximum Response Tmax | 4.00 hour |
| 16.6 mg Ferric Maltol | Transferrin Saturation Day 1, Time to Maximum Response Tmax | 3.00 hour |
| 7.8 mg Ferric Maltol | Transferrin Saturation Day 1, Time to Maximum Response Tmax | 3.00 hour |
Secondary
Change From Baseline to Day 10 in Absolute Reticulocyte Count
Change from Baseline to Day 10 in Absolute Reticulocyte Count collected from PK samples
Time frame: Change calculated as difference in values measured at Screening (Baseline) and on Day 10.
Population: ITT. Only subjects who had baseline samples and Day 10 samples taken.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Change From Baseline to Day 10 in Absolute Reticulocyte Count | 0.036 cells*10^12/L | Standard Deviation 0.0114 |
| 16.6 mg Ferric Maltol | Change From Baseline to Day 10 in Absolute Reticulocyte Count | -0.001 cells*10^12/L | Standard Deviation 0.0218 |
| 7.8 mg Ferric Maltol | Change From Baseline to Day 10 in Absolute Reticulocyte Count | 0.016 cells*10^12/L | Standard Deviation 0.0358 |
Secondary
Change From Baseline to Day 10 in Haemoglobin Concentration
Change calculated as difference in values measured at Screening (Baseline) and on Day 10
Time frame: Screening and Day 10 (1-4 hours post-dose)
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Change From Baseline to Day 10 in Haemoglobin Concentration | -0.03 g/dL | Standard Deviation 0.789 |
| 16.6 mg Ferric Maltol | Change From Baseline to Day 10 in Haemoglobin Concentration | -0.33 g/dL | Standard Deviation 1.097 |
| 7.8 mg Ferric Maltol | Change From Baseline to Day 10 in Haemoglobin Concentration | -0.45 g/dL | Standard Deviation 0.301 |
Secondary
Changes in 12-lead ECG Parameters From Screening to Day 10
Overall clinical interpretation of routine ECG parameters from Screening to Day 10
Time frame: Screening and Day 10 (1-4 hours post-dose)
Population: Safety population. Subjects who had ECG performed at both visits.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 30 mg Ferric Maltol | Changes in 12-lead ECG Parameters From Screening to Day 10 | Abnormal | 0 Participants |
| 30 mg Ferric Maltol | Changes in 12-lead ECG Parameters From Screening to Day 10 | Normal | 10 Participants |
| 16.6 mg Ferric Maltol | Changes in 12-lead ECG Parameters From Screening to Day 10 | Abnormal | 0 Participants |
| 16.6 mg Ferric Maltol | Changes in 12-lead ECG Parameters From Screening to Day 10 | Normal | 11 Participants |
| 7.8 mg Ferric Maltol | Changes in 12-lead ECG Parameters From Screening to Day 10 | Normal | 12 Participants |
| 7.8 mg Ferric Maltol | Changes in 12-lead ECG Parameters From Screening to Day 10 | Abnormal | 0 Participants |
Secondary
Concomitant Medications
Number of subjects with concomitant medications Taken by \>5% of Subjects
Time frame: Screening, Day 1, Day 10 and Post-Study Follow-up visit, on average 4 weeks
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Ferric Maltol | Concomitant Medications | 8 Participants |
| 16.6 mg Ferric Maltol | Concomitant Medications | 13 Participants |
| 7.8 mg Ferric Maltol | Concomitant Medications | 10 Participants |
Secondary
Ferritin - Change From Baseline to Day 10, Predose
Change calculated as difference in values measured at Day 1, predose (Baseline) and on Day 10, predose.
Time frame: Pre-dose on Day 1 to Day 10 (0h)
Population: ITT. Only subjects who had baseline samples taken on each PK day.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Ferritin - Change From Baseline to Day 10, Predose | 7.3 μg/L | Standard Deviation 8.22 |
| 16.6 mg Ferric Maltol | Ferritin - Change From Baseline to Day 10, Predose | 4.1 μg/L | Standard Deviation 3.73 |
| 7.8 mg Ferric Maltol | Ferritin - Change From Baseline to Day 10, Predose | 0.5 μg/L | Standard Deviation 4.95 |
Secondary
Negative and Positive NTBI Tests on Day 1
Negative and Positive Non-Transferrin Bound Iron \[NTBI\] tests on Day 1, predose
Time frame: Day 1 (0h)
Population: ITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 30 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 1 | Positive | 0 Participants |
| 30 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 1 | Negative | 12 Participants |
| 16.6 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 1 | Positive | 0 Participants |
| 16.6 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 1 | Negative | 13 Participants |
| 7.8 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 1 | Positive | 0 Participants |
| 7.8 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 1 | Negative | 12 Participants |
Secondary
Negative and Positive NTBI Tests on Day 10, Predose
Negative and Positive Non-Transferrin Bound Iron \[NTBI\] tests on Day 10, predose
Time frame: Day 10
Population: ITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 30 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 10, Predose | Positive | 1 Participants |
| 30 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 10, Predose | Negative | 11 Participants |
| 16.6 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 10, Predose | Positive | 0 Participants |
| 16.6 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 10, Predose | Negative | 11 Participants |
| 7.8 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 10, Predose | Positive | 0 Participants |
| 7.8 mg Ferric Maltol | Negative and Positive NTBI Tests on Day 10, Predose | Negative | 10 Participants |
Secondary
Total Iron Binding Capacity - Change From Day 1 to Day 10, Predose
Change calculated as difference in values measured at Day 1, predose and on Day 10, predose
Time frame: Predose from Day 1 to Day 10 (0h on each day)
Population: ITT. Only subjects who had baseline samples taken on each PK day.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Total Iron Binding Capacity - Change From Day 1 to Day 10, Predose | -2.12 umol/L | Standard Deviation 3.406 |
| 16.6 mg Ferric Maltol | Total Iron Binding Capacity - Change From Day 1 to Day 10, Predose | -3.11 umol/L | Standard Deviation 3.201 |
| 7.8 mg Ferric Maltol | Total Iron Binding Capacity - Change From Day 1 to Day 10, Predose | 1.13 umol/L | Standard Deviation 4.452 |
Secondary
Transferrin - Change From Baseline to Day 10, Predose
Change calculated as difference in values measured at Day 1, predose (Baseline) and on Day 10, predose
Time frame: Day 1 pre-dose to Day 10 pre-dose (0h on each day)
Population: ITT. Only subjects who had baseline samples taken on each PK day.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | Transferrin - Change From Baseline to Day 10, Predose | -0.085 g/L | Standard Deviation 0.151 |
| 16.6 mg Ferric Maltol | Transferrin - Change From Baseline to Day 10, Predose | -0.147 g/L | Standard Deviation 0.1419 |
| 7.8 mg Ferric Maltol | Transferrin - Change From Baseline to Day 10, Predose | 0.032 g/L | Standard Deviation 0.2275 |
Secondary
Treatment-emergent Adverse Events (AEs) Leading to Premature Discontinuation of Study Drug/PK Assessments
Descriptive summary of incidence and causal relationship of treatment-emergent adverse events leading to discontinuation of study drug/PK assessments according to MedDRA preferred term (PT) and system organ class (SOC)
Time frame: From first dose of Ferric Maltol on Day 1 through study completion, on average 4 weeks
Population: screened population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Ferric Maltol | Treatment-emergent Adverse Events (AEs) Leading to Premature Discontinuation of Study Drug/PK Assessments | 0 Participants |
| 16.6 mg Ferric Maltol | Treatment-emergent Adverse Events (AEs) Leading to Premature Discontinuation of Study Drug/PK Assessments | 1 Participants |
| 7.8 mg Ferric Maltol | Treatment-emergent Adverse Events (AEs) Leading to Premature Discontinuation of Study Drug/PK Assessments | 0 Participants |
Secondary
Treatment-emergent Serious Adverse Event (TESAE)
Descriptive summary of TESAE according to MedDRA preferred Term
Time frame: From first dose of ferric maltol Day 1 through study completions, on average 4 weeks
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 30 mg Ferric Maltol | Treatment-emergent Serious Adverse Event (TESAE) | 0 Participants |
| 16.6 mg Ferric Maltol | Treatment-emergent Serious Adverse Event (TESAE) | 0 Participants |
| 7.8 mg Ferric Maltol | Treatment-emergent Serious Adverse Event (TESAE) | 0 Participants |
Secondary
UIBC - Change From Day 1 to Day 10, Predose
Change calculated as difference in values measured at Day 1, predose and on Day 10, predose
Time frame: Pre-dose on Day 1 to Day 10 (0h each day)
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 30 mg Ferric Maltol | UIBC - Change From Day 1 to Day 10, Predose | -2.10 umol/L | Standard Deviation 7.775 |
| 16.6 mg Ferric Maltol | UIBC - Change From Day 1 to Day 10, Predose | -2.33 umol/L | Standard Deviation 5.525 |
| 7.8 mg Ferric Maltol | UIBC - Change From Day 1 to Day 10, Predose | -4.49 umol/L | Standard Deviation 8.343 |