Pharmacokinetics of Triferic (Ferric Pyrophosphate Citrate) Administered Intravenously to Healthy Adult Volunteers

Phase 1

Completed

Conditions: End Stage Renal Disease

Interventions: Drug: Triferic

Registration Number: NCT02636049

Lead Sponsor: Rockwell Medical Technologies, Inc.

Brief Summary: This is a Phase 1, open-label, three-period sequential dosing study being conducted to determine the pharmacokinetics of Triferic iron administered intravenously (IV) to healthy adults.

Detailed Description: This is a Phase 1, open-label, three-period sequential dosing study being conducted primarily to determine the pharmacokinetics of Triferic iron administered intravenously to healthy adults.. Participation will be up to 5 weeks total duration including Screening, Baseline, Treatment Period, and Follow-up. Following Screening, subjects will be admitted to the clinic on Day -1, prior to Baseline (Day 1). During the Treatment Period, subjects will receive two doses of Triferic. Each subject will receive a single 6-mg dose of Triferic administered IV over 3 hours (hr) on one day (Day 2), and a single 35-µg/kg dose of Triferic administered IV push the following day (Day 3). On Day 4, subjects will be discharged from the clinic and will return approximately one week later for their final Follow-up visit.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

Inclusion Criteria

Subjects must meet all of the following criteria to be eligible for inclusion in the study:

The subject 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 subject must be 18-65 years of age inclusive at the time of consent.
The subject must have a transferrin saturation (TSAT) of 15-50% during Screening.
The subject must agree to discontinue all iron preparations for 14 days prior to Baseline.
If the subject is female, she must be premenopausal, 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 subject must be willing and able to comply with all study procedures and restrictions.
The subject must have no clinically-significant abnormal findings on medical history, vital signs, physical examination, or clinical laboratory results during Screening.
The subject must have a body mass index (BMI) of ≤32.0 kg/m2 at Screening and weigh >60.0 kg.

Exclusion Criteria

A subject will not be eligible for inclusion in the study if any of the following criteria apply:

The subject has a hemoglobin (Hgb) concentration <13.0 g/dL for men or <12 g/dL for women during Screening.
The subject has a total iron binding capacity (TIBC) <250 µg/dL during Screening.
The subject has had administration of IV or oral iron supplements (including multivitamins with iron) within 14 days prior to Baseline.
Subject 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.
Subject has a C-reactive protein level (CRP) >5 mg/L during Screening, or any rheumatic or autoimmune disease that requires systemic anti-inflammatory or immunomodulatory therapy.
Subject has an acute illness within 14 days prior to Baseline.
Subject has known or suspected intolerance or hypersensitivity to iron-containing products.
Subject has a history of alcohol or substance abuse within the past year.
Subject has a positive screen for cotinine or drugs of abuse.
Subject is positive for HIV, hepatitis B, or hepatitis C.
Subject uses tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g., gum, patch, etc.). Ex-users must report that they have stopped using tobacco for at least 30 days prior to Baseline.
Subject donated blood or blood products (e.g., plasma or platelets) within 60 days prior to Baseline.
Subject participated in an investigational drug study within 30 days prior to Baseline.
Subject is pregnant or intends to become pregnant before completing the study.
Subject's current medical status, in the investigator's opinion, would preclude participation in the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment Period: 35 micrograms/kg IV push	Triferic	Each subject will receive Triferic as 35 µg/kg body weight IV push over 30-60 seconds on Day 3. The Triferic IV push dosing solution will have been prepared by diluting Triferic from ampules (5.44 mg/mL) in an appropriate amount of D5W to a concentration of 35 µg Triferic iron/kg body weight per subject in 4.5 mL.
Treatment Period: 6 mg Triferic IV over 3 hours	Triferic	Each subject will receive a single 6 mg dose of Triferic administered as a continuous intravenous infusion over 3 hours on Day 2. The Triferic IV dosing solution will have been prepared by diluting Triferic from ampules (5.44 mg/mL) in an appropriate amount of D5W to a concentration of 0.020 mg/mL. Administration of 300 mL IV at 100 mL/hr for 3 hours results in delivery of 6 mg of Triferic iron.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics of Triferic Iron Administered IV to Healthy Adults: Maximum Drug Concentration (Cmax) of Total Serum Iron	16 hours	Blood samples will be drawn at time = 0, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12, and 16 hours after the start of Triferic administration on study Day 2 (IV infusion of 6 mg Triferic over 3 hours) and Day 3 (35 microgram/kg IV dose of Triferic given over 30 - 60 seconds) in order to determine the Peak Serum Concentration, corrected (Cmax) of total serum iron.
Pharmacokinetics of Triferic Iron Administered IV to Healthy Adults: Area Under the Serum Iron Concentration Time Curve From Time Zero to the Time of Last Quantified Concentration (AUC(Last)) of Total Serum Iron	16 hours	Blood samples will be drawn at time = 0, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 8, 12, and 16 hours after the start of Triferic administration on study Day 2 (IV infusion of 6 mg Triferic over 3 hours) and study day 3 (35 microgram/kg IV Triferic dose administered in 30 - 60 seconds) in order to determine the AUC(last) of total serum iron.

Secondary Outcome Measures

Name	Time	Method
Incidence of Treatment Emergent Adverse Events	10 - 14 days	The number of patients that experienced treatment emergent adverse events will be quantified.
Incidence of Treatment Emergent Serious Adverse Events	10 - 14 days	The number of patients that experienced treatment emergent serious adverse events (TESEAs) will be quantified.