Four-Way Crossover Study to Compare Ferric Maltol Capsules and Oral Suspension in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of the study is to compare the Pharmacokinetics (PK) of the new ferric maltol suspension, in adults, with the existing ferric maltol capsule.

Detailed Description
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Open-label, Phase 1, four way crossover study to compare the PK of the new ferric maltol suspension, in healthy volunteers, with the existing ferric maltol capsules under fed and fasted conditions. 32 subjects will be randomised to 1:1:1:1 ratio to receive one of the treatment sequences. Based on the randomised sequence, subjects will receive a single dose of 30mg ferric maltol capsule in a fed/ fasted condition and 30 mg (5ml) ferric maltol suspension in a fed/ fasted condition. Subject participation in the study will consist of 3 periods: Screening: up to 14 days Randomised treatment: 8 days Post-treatment follow up: 3-7 days following drug discontinuation

Official Title
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A Randomized, Open-Label, Single Dose, Four-Way Crossover, Phase I Study to Compare the Pharmacokinetics of Ferric Maltol Capsules and Oral Suspension Under Fasted and Fed Conditions in Adult Healthy Volunteers

Conditions
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Anemia, Iron Deficiency

Intervention / Treatment
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* Drug: Ferric maltol capsule
* Drug: Ferric maltol suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All of the following criteria must be met for a subject to participate in the study: Must voluntarily sign and date each Institutional Review Board (IRB)-approved informed consent form (ICF) prior to the initiation of any screening or study-specific procedures. Willing and able to comply with study requirements. Healthy adult subjects 18 to 55 years of age, inclusive at the time of informed consent. Body Mass Index (BMI) of 18-32 kg/m2 inclusive Female subjects of childbearing potential must not be planning a pregnancy or be pregnant or lactating. All female subjects must have a negative result for the pregnancy tests performed at screening and each treatment period. Female subjects of childbearing potential (including perimenopausal females who have had a menstrual period within 1 year prior to screening) 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 hormonal contraception (oral, implants, injection, ring, or patch) and intrauterine contraceptive devices (IUDs), at least 3 months prior to Screening, or a vasectomized partner. Note: complete abstinence from sexual intercourse is an acceptable form of contraceptive practice. Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral, tubal ligation, bilateral salpingectomy, and/or bilateral oophorectomy at least 26 weeks before the Screening Visit) or post-menopausal, defined as spontaneous amenorrhea for at least 2 years Male subjects with partners of childbearing potential must have had surgical sterilization (vasectomy) at least 26 weeks prior to Screening or use a male barrier method of contraception (i.e. male condom with spermicide) during any sexual intercourse from Study Day -1 (beginning of confinement) until 3 months after the Follow-up Visit. Note: Complete abstinence from sexual intercourse is an acceptable form of contraceptive practice. Male subjects must agree to abstain from sperm donation from initial study drug administration through 3 months after administration of the last dose of study drug. Exclusion Criteria: A subject who meets any of the following criteria is not eligible for participation in the study. Known hypersensitivity or allergy to the active substance or excipients of Ferric maltol oral suspension or capsules; Presence or history of any significant cardiovascular, gastrointestinal, hepatic, renal, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurological, or psychiatric disease, as determined by the Investigator; Presence or history of any other condition (including surgery) known to interfere with the absorption, distribution, metabolism, or excretion of medicines; Recent (within 6 months of screening) history of drug or alcohol abuse; Positive screen results for drugs of abuse, alcohol at screening or Study Day -1 of Period1; Consumption of alcohol within 72 hrs prior to study drug administration; Positive test result for hepatitis B surface antigen (HBSaAg), hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening; Donation or loss of 550 mL or more blood volume or receipt of a transfusions of any blood product within 8 weeks prior to study drug administration and 14 days for plasma donation unless medically inadvisable; Use of any over the counter medications, including herbal product within 7 days prior to Screening until study completion. Except for ordinary pain (e.g. headache), some analgesics (mainly paracetamol) and contraception which have no drug interactions with the study products may be given; Has received within 28 days prior to Screening intramuscular or intravenous (IV) injection or administration of depot iron preparation; Has received oral iron supplementation within 7 days prior to Screening; Has concomitant disease that would significantly compromise iron absorption or absorbed iron utilization such as swallowing disorders, gastric pH-disturbance and/or extensive small bowel resection; Scheduled or expected hospitalization and/or surgery during the course of the study; Diagnosed to be COVID-19 positive by polymerase chain reaction testing (SARS-CoV-2-RTPCR positive) of a respiratory specimen (preferably a nasopharyngeal swab) on Day -2; Participation in any other interventional clinical study within 28 days prior to Screening; Any other unspecified reason that, in the opinion of the Investigator or the Sponsor makes the subject unsuitable for enrolment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Subjects will be randomized 1:1:1:1 to one of the treatment sequences. ie. single dose of 30 mg ferric maltol capsule in a fed condition single dose of 30 mg (5 ml) ferric maltol suspension in a fed condition single dose of 30 mg ferric maltol capsule in a fasted condition single dose of 30 mg (5 ml) ferric maltol suspension in a fasted condition
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 30 mg ferric maltol capsule in a fed condition<br>Single dose of 30 mg ferric maltol capsule in a fed condition | Drug: Ferric maltol capsule<br>* single dose of 30 mg capsule<br>* Other names: Accrufer;|
| Active Comparator: 30 mg ferric maltol capsule in a fasted condition<br>Single dose of 30 mg ferric maltol capsule in a fasted condition | Drug: Ferric maltol capsule<br>* single dose of 30 mg capsule<br>* Other names: Accrufer;|
| Experimental: 30 mg (5 ml) ferric maltol suspension in a fed condition<br>Single dose of 30 mg (5 ml) ferric maltol suspension in a fed condition | Drug: Ferric maltol suspension<br>* single dose of 30mg (5ml) oral suspension<br>* Other names: ST10;|
| Experimental: 30 mg (5 ml) ferric maltol suspension in a fasted condition<br>Single dose of 30 mg (5 ml) ferric maltol suspension in a fasted condition | Drug: Ferric maltol suspension<br>* single dose of 30mg (5ml) oral suspension<br>* Other names: ST10;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of maximum serum concentration (Cmax) of total iron in fasted condition | Ratio of maximum serum concentration (Cmax) of total iron in combined periods of fasted condition between ferric maltol capsule and ferric maltol suspension. | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose in combined fasted condition | 
| Ratio of maximum serum concentration (Cmax) of total iron in combined periods of fed condition | Ratio of maximum serum concentration (Cmax) of total iron in combined periods of fed condition between ferric maltol capsule and ferric maltol suspension | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose in combined fed condition | 
| Ratio of area under the curve (AUClast) of total serum iron in combined period of fasted condition | Ratio of area under the curve (AUClast) of total serum iron in combined periods of fasted condition between ferric maltol capsule and ferric maltol suspension | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose in combined fasted condition | 
| Ratio of area under the curve (AUClast) of total serum iron in combined period of fed condition | Ratio of area under the curve (AUClast) of total serum iron in combined periods of fed condition between ferric maltol capsule and ferric maltol suspension | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose in combined fed condition | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK analysis of total serum iron concentration; AUCinf in fasted and fed conditions | Descriptive statistics of total serum iron concentration; Area Under the Curve (AUCinf) by formulation (suspension or capsule) and condition (fed and fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of baseline corrected serum iron concentration; Cmax in fasted and fed conditions | Descriptive statistics of baseline corrected serum iron concentration; Maximum Concentration (Cmax), by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of baseline corrected serum iron concentration; AUClast in fasted and fed conditions | Descriptive statistics of baseline corrected serum iron concentration; area under the Curve from pre-dose to last measurable concentration by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of baseline corrected serum iron concentration; AUCinf in fasted and fed conditions | Descriptive statistics of baseline corrected serum iron concentration; Area Under the Curve from 0-infinity by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of maltol glucuronide; Cmax in fasted and fed conditions | Descriptive statistics of Maximum plasma Concentration (Cmax) of plasma maltol glucuronide by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of maltol glucuronide; AUClast in fasted and fed conditions | Descriptive statistics of maltol glucuronide; Area Under the Curve from pre-dose to last measurable concentration by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of maltol; Cmax in fasted and fed conditions | Descriptive statistics of Maximum plasma Concentration (Cmax) of plasma maltol by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of maltol; AUClastin fasted and fed conditions | Descriptive statistics of maltol; Area Under the Curve from pre-dose to last measurable concentration by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of TSAT; Cmax in fasted and fed conditions | Descriptive statistics of Maximum Concentration (Cmax) of transferrin saturation by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of TSAT; AUClast in fasted and fed conditions | Descriptive statistics of transferrin saturation; Area Under the Curve from pre-dose to last measurable concentration by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of TIBC; Cmax in fasted and fed conditions | Descriptive statistics of Maximum Concentration (Cmax) of Total Iron Binding Capacity (TIBC) by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of TIBC; AUClast in fasted and fed conditions | Descriptive statistics of Total Iron Binding Capacity (TIBC); Area Under the Curve from pre-dose to last measurable concentration by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| Summary of Serious Adverse Events | Descriptive statistics of Serious Adverse Events by formulation (suspension or capsule) and condition (fed and fasted) | up to 2 weeks following last dose | 
| PK analysis of UIBC; Cmax in fasted and fed conditions | Descriptive statistics of Maximum Concentration (Cmax) of Unsaturated Iron Binding Capacity (UIBC) by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of UIBC; AUClast in fasted and fed conditions | Descriptive statistics of Unsaturated Iron Binding Capacity (TIBC); Area Under the Curve from pre-dose to last measurable concentration by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of transferrin; Cmax in fasted and fed conditions | Descriptive statistics of transferrin; Maximum concentration (Cmax) from pre-dose to last measurable concentration by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| PK analysis of transferrin; AUClast in fasted and fed conditions | Descriptive statistics of transferrin; Area Under the Curve from pre-dose to last measurable concentration by formulation (suspension or capsule) and condition (fed or fasted) | Pre-dose and 0.15, 0.30, 0.45, 1, 2, 3, 4, 6, 10 and 24 hours post-dose | 
| Changes in Hb from screening to Day 8 | Changes in Haemoglobin; change calculated as difference in values measured at Screening, predose and on Day 8, pre-dose by formulation (suspension or capsule) and condition (fed or fasted) | Screening to Day 8 | 
| Treatment-Emergent Adverse Events | Descriptive summary of incidence and casual relationship of treatment-emergent serious adverse events according to MedDRA preferred term (PT) and system organ class (SOC) | From first dose of ferric maltol on Day 1 to study completion | 
| TEAE leading to premature discontinuation of study drug/PK assessments | Descriptive summary of incidence and casual 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) | From first dose of ferric maltol on Day 1 to study completion | 
| Vital signs - blood pressure, change from Day 1 to Day 8, Pre-dose | Descriptive statistics for changes in blood pressure from Screening to Day 8 | Screening to Day 8 | 
| Vital signs - heart rate, change from Day 1 to Day 8, Pre-dose | Descriptive statistics for changes in heart rate from Screening to Day 8 | Screening to Day 8 | 
| Summary of concomitant medication by formulation | Number of concomitant medications by formulation (suspension or capsule) | Day 1 to Day 8 (24 hrs post-dose of last dosing) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iron deficiency, anaemia