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

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.

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.