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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fer-In-Sol Orally | Experimental | Patients will receive A single oral dose of Fer-In-Sol at 3 mg Fe/kg body weight (bw). |
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| Shohl's solution followed by Fer-In-Sol Orally | Experimental | 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. |
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| Triferic Orally | Experimental | Patients will receive a single oral dose of Triferic at 3 mg Fe/kg bw. |
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| Shohl's solution followed by Triferic Orally | Experimental | 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. |
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| Shohl's solution followed immediately by Triferic | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Triferic | Drug |
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| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Raymond D Pratt, MD, FACP | Rockwell Medical, Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jasper Clinic | Kalamazoo | Michigan | 49071 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants | This is a cross-over pharmacokinetic (PK) study where all participants underwent baseline blood sampling over 24 hours for PK purposes followed by five different oral treatments in a randomized sequence: Fer-In-Sol 3 mg Fe/kg, Shohl's solution 0.7 mL/kg followed 10 minutes later by Fer-In-Sol 3 mg Fe/kg, Triferic 3 mg Fe/kg, Shohl's solution 0.7 mL/kg followed 10 minutes later by Triferic 3 mg Fe/kg, and Shohl's solution 0.7 mL/kg followed immediately by Triferic 3 mg Fe/kg. 24 blood sampling for PK purposes took place at each randomized treatment visit. Once the randomized sequence was completed, all subjects were administered 6.6 mg Triferic intravenously at the last treatment visit, with blood sampling for PK purposes over 24 hours. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Triferic via IV | Experimental | 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. |
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| Baseline | No Intervention | baseline serum iron profile will be determined for each patient. no study drug will be administered. |
| Fer-In-Sol | Drug |
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| Shohl's solution | Drug |
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The number of participants in each treatment group who experienced treatment emergent serious adverse events will be quantified. |
| 13 days |
| Baseline |
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| Fer-In-Sol |
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| Shohl's + Fer-In-Sol |
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| Triferic |
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| Shohl's + Triferic After 10 Min |
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| Shohl's + Triferic Immediately |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Safety Population | All 14 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Body Mass Index | Mean | Standard Deviation | Kilogram/square meter |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | 14 patients completed all six treatments. While all participants had adequate blood samples collected to be included in pharmacokinetic analysis, some samples were below the quantifiable limit (BLQ) of the bioanalytical assay, which was 50 micrograms/deciliter. Therefore, number of participants analyzed for each treatment does not equal 14. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram/deciliter | 0, 1, 2, 4, 6, 8, 12, 16, and 24 hours |
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| Secondary | 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. | Safety Population: all enrolled subjects who received at least one dose of study drug. | Posted | Count of Participants | Participants | 13 days |
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| Secondary | 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. | Safety Population: all enrolled subjects who received at least one dose of study drug. | Posted | Count of Participants | Participants | 13 days |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Fer-In-Sol Orally | Patients will receive A single oral dose of Fer-In-Sol at 3 mg Fe/kg body weight (bw). | 0 | 14 | 0 | 14 | 7 | 14 |
| EG001 | Shohl's Solution Followed by Fer-In-Sol Orally | 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. | 0 | 14 | 0 | 14 | 5 | 14 |
| EG002 | Triferic Orally | Patients will receive a single oral dose of Triferic at 3 mg Fe/kg bw. | 0 | 14 | 0 | 14 | 2 | 14 |
| EG003 | Shohl's Solution Followed by Triferic Orally | 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. | 0 | 14 | 0 | 14 | 6 | 14 |
| EG004 | Shohl's Solution Followed Immediately by Triferic | 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. | 0 | 14 | 0 | 14 | 6 | 14 |
| EG005 | Triferic Via IV | 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. | 0 | 14 | 0 | 14 | 2 | 14 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Discomfort | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal Distension | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal Pain Lower | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal Pain Upper | Gastrointestinal disorders | Systematic Assessment |
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| Defaecation Urgency | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Flatuence | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Discomfort | General disorders | Systematic Assessment |
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| Vessel Puncture Site Swelling | General disorders | Systematic Assessment |
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| Muscle Spasms | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Presyncope | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Project Manager | Rockwell Medical, Inc | 248-960-9009 | sgrimberg@rockwellmed.com |
| ID | Term |
|---|---|
| C562385 | Iron-Refractory Iron Deficiency Anemia |
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| ID | Term |
|---|---|
| C049051 | ferric pyrophosphate |
| C032360 | spleen fibrinolytic proteinase (human) |
| C020748 | ferrous sulfate |
| D002951 | Citrates |
| ID | Term |
|---|---|
| D014233 | Tricarboxylic Acids |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| OG004 | Treatment E | 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. |
| OG005 | Treatment F | 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. |
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| OG004 | Treatment E | 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. |
| OG005 | Treatment F | 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. |
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