Pharmacokinetics and Absolute Bioavailability of Fer-In-Sol and Triferic Administered Orally With Shohl's Solution in Healthy Volunteers

Study Overview
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Brief Summary
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The main purpose is to determine the pharmacokinetics (PK) of Triferic iron administered orally in healthy adult volunteers. It is a randomized multiple treatments, single dose study.

Detailed Description
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This is a Phase 1/2, randomized multiple treatments, single dose study assessing the pharmacokinetics (PK) and absolute bioavailability of Fer-In-Sol ( Ferrous Sulfate) and Triferic (ferric pyrophosphate citrate, or FPC) administered orally with Shohl's solution in healthy volunteers. Total participation in the study is approximately six weeks and is comprised of a screening visit, 6 treatment periods, and a follow-up visit. The study will be conducted over a 13 day period: Day 1 will used to determine the baseline serum iron profile for each subject. Each subject will subsequently receive in a randomized sequence between Day 2 and 10: A single oral dose of Fer-In-Sol at 3 mg Fe/kg body weight (bw). A single oral dose of Oracit Shohl's solution 0.67 mEq/L (0.7 ml/kg bw) followed after 10 minutes by Fer-In-Sol at 3 mg Fe/kg bw a single oral dose of Triferic PO at 3 mg Fe/kg bw a single oral dose of Oracit Shohl's solution 0.67 mEq/L (0.7 ml/kg bw) administered 10 minutes prior to a single oral dose of Triferic at 3 mg Fe/kg bw. a single oral dose of Oracit Shohl's solution 0.67 mEq/L (0.7 ml/kg bw) followed immediately by a single oral dose of Triferic at 3 mg Fe/kg bw. All subjects will receive a single dose of 6.6 mg Triferic as a 4 hour IV infusion (to mimic the 4 hour iron tolerance test) on Day 12. Blood samples will be obtained at various times to analyze for serum iron parameters and for safety.

Official Title
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Pharmacokinetics and Absolute Bioavailability of Fer-In-Sol (Ferrous Sulfate) and Triferic (Ferric Pyrophosphate Citrate) Administered Orally With Shohl's Solution in Healthy Volunteers

Conditions
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Iron-refractory, Iron-deficiency Anemia (IRIDA)

Intervention / Treatment
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* Drug: Triferic
* Drug: Fer-In-Sol
* Drug: Shohl's solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must be able to provide informed consent and have personally signed and dated the study written informed consent document before completing any study-related procedures. The patient has hemoglobin, MCV and reticulocyte values within the reference range for gender. (Male: Hgb ≥13.0 g/dL; Female Hgb ≥ 12.0 g/dL) at Screening. The patient must have transferrin saturation (TSAT) of ≥20% at Screening. The patient must have a total iron binding capacity (TIBC) of ≥250 ug/dL at Screening. The patient must have a serum ferritin within the following reference range for gender at Screening: (Males: 23-336 ng/mL; Females: 11-306 ng/mL). The patient must agree to discontinue all iron preparations for 14 days prior to Baseline. If the patient is female, she must be non-pregnant and non-lactating, and be at least 90 days post-partum (if applicable) at Screening. Women of childbearing potential must be willing to use appropriate birth control during the entire duration of the study. The patient must be willing and able to comply with all study procedures and restrictions. The patient must have no clinically significant abnormal findings on medical history, vital signs, physical examination, or clinical laboratory results during Screening. The patient must have a body mass index (BMI) of ≤35.0 kg/m2 at Screening. Exclusion Criteria: The patient has had administration of oral iron supplements within 14 days prior to Baseline. The patient has received IV iron within 6 months prior to Screening. The patient has a serum CRP concentration above the upper limit of normal at Screening or Baseline (> 6.0 mg/L). The patient has concurrent or recurrent disease (e.g., cardiovascular, renal, hepatic, gastrointestinal, malignant, etc.) that could affect the action or disposition of the investigational product utilized in this study, or could affect clinical or laboratory assessments. The patient has an acute illness within 14 days prior to Baseline. The patient is currently using any medication (including prescription, over-the-counter (OTC), herbal, or homeopathic preparations) within 14 days prior to Baseline. Exceptions are contraceptives, hormone replacement therapy, acetaminophen, and non-steroidal anti-inflammatory drugs. The patient has known or suspected intolerance or hypersensitivity to iron-containing products. The patient has a history of alcohol or substance abuse within the past year. The patient has a positive screen for cotinine or drugs of abuse. The patient is positive for HIV, hepatitis B, or hepatitis C by history. The patient donated blood or blood products (e.g., plasma or platelets) within 30 days prior to Screening. The patient has participated in an investigational drug study within 30 days prior to Screening. The patient is pregnant or intends to become pregnant before completing the study. The patient's current medical status, in the investigator's opinion, would preclude participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fer-In-Sol Orally<br>Patients will receive A single oral dose of Fer-In-Sol at 3 mg Fe/kg body weight (bw). | Drug: Fer-In-Sol<br> <br> * Other names: Ferrous Sulfate;|
| Experimental: Shohl's solution followed by Fer-In-Sol Orally<br>Patients will receive a single oral dose of Oracit Shohl's solution 0.67 mEq/L (0.7ml/kg bw) followed after 10 minutes by Fer-In-Sol at 3 mg Fe/kg bw. | Drug: Fer-In-Sol<br> <br> * Other names: Ferrous Sulfate;Drug: Shohl's solution<br> <br> * Other names: Oracit;|
| Experimental: Triferic Orally<br>Patients will receive a single oral dose of Triferic at 3 mg Fe/kg bw. | Drug: Triferic<br> <br> * Other names: FPC;|
| Experimental: Shohl's solution followed by Triferic Orally<br>Patients will receive a single oral dose of Oracit Shohl's solution 0.67 mEq/L (0.7 ml/kg bw) administered 10 minutes prior to a single oral dose of Triferic at 3 mg Fe/kg bw. | Drug: Triferic<br> <br> * Other names: FPC;Drug: Shohl's solution<br> <br> * Other names: Oracit;|
| Experimental: Shohl's solution followed immediately by Triferic<br>Patients will receive a single oral dose of Oracit Shohl's solution 0.67 mEq/L (0.7 ml/kg bw) followed immediately by a single oral dose of Triferic at 3 mg Fe/kg bw. | Drug: Triferic<br> <br> * Other names: FPC;Drug: Shohl's solution<br> <br> * Other names: Oracit;|
| Experimental: Triferic via IV<br>Patients will receive IV Triferic iron 6.6 mg diluted in an appropriate amount of D5W administered as a 120 mL infusion intravenously for 4 hours. | Drug: Triferic<br> <br> * Other names: FPC;|
| No Intervention: Baseline<br>baseline serum iron profile will be determined for each patient. no study drug will be administered. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of Total Iron From Triferic Administered Orally in Adult Healthy Patients: Cmax | The outcome will be measured by assessing the Cmax of total iron with multiple different oral iron treatment. The following oral iron dosing treatments will be measured: Treatment A (Fer-in-Sol 3 mg iron/kg), Treatment B (Shohl's solution followed after 10 minutes by Fer-In-Sol, 3 mg/kg), Treatment C (Triferic 3 mg iron/kg), Treatment D (Shohl's solution followed after 10 minutes by Triferic 3 mg/kg), Treatment E (Shohl's solution followed immediately by Triferic 3 mg/kg), Treatment F (Triferic 6.6 mg IV over 4 hours) | 0, 1, 2, 4, 6, 8, 12, 16, and 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | The number of participants in each treatment group who experienced treatment emergent adverse events will be quantified. | 13 days | 
| Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) | The number of participants in each treatment group who experienced treatment emergent serious adverse events will be quantified. | 13 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, healthy adult volunteer