End Stage Renal Disease
Conditions
Keywords
pharmacokinetics, healthy adult volunteer
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.
Interventions
DRUGTriferic
Triferic is supplied as sterile 5 mL ampules containing 5.44 mg/mL of iron in water for injection. Each 5 mL ampule contains 27.2 mg of Triferic iron.
Sponsors
Rockwell Medical Technologies, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects must meet all of the following criteria to be eligible for inclusion in the study: 1. 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. 2. The subject must be 18-65 years of age inclusive at the time of consent. 3. The subject must have a transferrin saturation (TSAT) of 15-50% during Screening. 4. The subject must agree to discontinue all iron preparations for 14 days prior to Baseline. 5. 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. 6. The subject must be willing and able to comply with all study procedures and restrictions. 7. The subject must have no clinically-significant abnormal findings on medical history, vital signs, physical examination, or clinical laboratory results during Screening. 8. 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: 1. The subject has a hemoglobin (Hgb) concentration \<13.0 g/dL for men or \<12 g/dL for women during Screening. 2. The subject has a total iron binding capacity (TIBC) \<250 µg/dL during Screening. 3. The subject has had administration of IV or oral iron supplements (including multivitamins with iron) within 14 days prior to Baseline. 4. 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. 5. 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. 6. Subject has an acute illness within 14 days prior to Baseline. 7. Subject has known or suspected intolerance or hypersensitivity to iron-containing products. 8. Subject has a history of alcohol or substance abuse within the past year. 9. Subject has a positive screen for cotinine or drugs of abuse. 10. Subject is positive for HIV, hepatitis B, or hepatitis C. 11. 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. 12. Subject donated blood or blood products (e.g., plasma or platelets) within 60 days prior to Baseline. 13. Subject participated in an investigational drug study within 30 days prior to Baseline. 14. Subject is pregnant or intends to become pregnant before completing the study. 15. Subject's current medical status, in the investigator's opinion, would preclude participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Safety Population All 12 participants completed every arm of the study. Therefore, the baseline demographic characteristics of the Safety Population as a whole also reflect the characteristics of each arm of the study. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 38.4 years STANDARD_DEVIATION 8.99 |
| Body Mass Index | 26.07 Kilogram/square meter STANDARD_DEVIATION 2.592 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 179.61 centimeters STANDARD_DEVIATION 7.365 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 10 Participants |
| Weight | 84.48 kilogram STANDARD_DEVIATION 12.892 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 1 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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
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.
Time frame: 16 hours
Population: Pharmacokinetic population: all enrolled subjects who received at least 1 dose of study drug and had sufficient pharmacokinetic samples (a sample at the end of infusion and at least 3 samples during the elimination phase) for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period: 6 mg Triferic IV Over 3 Hours | 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 | 858 hour*microgram/deciliter | Geometric Coefficient of Variation 59.6 |
| Treatment Period: 35 Micrograms/kg IV Push | 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 | 175 hour*microgram/deciliter | Geometric Coefficient of Variation 234 |
Primary
Pharmacokinetics of Triferic Iron Administered IV to Healthy Adults: Maximum Drug Concentration (Cmax) of Total Serum Iron
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.
Time frame: 16 hours
Population: Pharmacokinetic population: all enrolled subjects who received at least 1 dose of study drug and had sufficient pharmacokinetic samples (a sample at the end of infusion and at least 3 samples during the elimination phase) for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period: 6 mg Triferic IV Over 3 Hours | Pharmacokinetics of Triferic Iron Administered IV to Healthy Adults: Maximum Drug Concentration (Cmax) of Total Serum Iron | 102 microgram/deciliter | Geometric Coefficient of Variation 40.1 |
| Treatment Period: 35 Micrograms/kg IV Push | Pharmacokinetics of Triferic Iron Administered IV to Healthy Adults: Maximum Drug Concentration (Cmax) of Total Serum Iron | 44.1 microgram/deciliter | Geometric Coefficient of Variation 71.9 |
Secondary
Incidence of Treatment Emergent Adverse Events
The number of patients that experienced treatment emergent adverse events will be quantified.
Time frame: 10 - 14 days
Population: Safety Population: all enrolled subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Period: 6 mg Triferic IV Over 3 Hours | Incidence of Treatment Emergent Adverse Events | 1 participants |
| Treatment Period: 35 Micrograms/kg IV Push | Incidence of Treatment Emergent Adverse Events | 1 participants |
Secondary
Incidence of Treatment Emergent Serious Adverse Events
The number of patients that experienced treatment emergent serious adverse events (TESEAs) will be quantified.
Time frame: 10 - 14 days
Population: Safety Population: all enrolled subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Period: 6 mg Triferic IV Over 3 Hours | Incidence of Treatment Emergent Serious Adverse Events | 0 participants |
| Treatment Period: 35 Micrograms/kg IV Push | Incidence of Treatment Emergent Serious Adverse Events | 0 participants |