Iron Deficiency, Iron Deficiency Anemia
Conditions
Keywords
CKD, Chronic Kidney Disease, Phosphorus, Iron Deficiency, Iron Deficiency Anemia, Elevated Phosphorus
Brief summary
The purpose of this study is to determine if KRX-0502 (ferric citrate) is a safe and effective treatment for the management of serum phosphorus levels and iron deficiency in anemic chronic kidney disease (CKD) stage 3-5 subjects not on dialysis. Total length of treatment is approximately 12 weeks.
Detailed description
This is a randomized, double-blind, placebo-controlled, three-period, multi-center clinical trial. Following a Screening and Qualification Period and a two-week Washout Period (for those subjects entering the study on a phosphate binder), eligible subjects will be randomized in a 1:1 ratio to receive either KRX-0502 (ferric citrate) or placebo for up to approximately 12 weeks. The purpose of this study is to determine if KRX-0502 (ferric citrate) is a safe and effective treatment for the management of serum phosphorus levels and iron deficiency in anemic CKD subjects not on dialysis.
Interventions
DRUGFerric Citrate
Dose depends on serum phosphorus levels collected at each study visit.
DRUGPlacebo
Sponsors
Keryx Biopharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage III to V Chronic Kidney Disease * Serum Phosphorus 4.0-6.0 mg/dL prior to Randomization * Ferritin 300 ng/mL or less * Transferrin Saturation (TSAT) 30% or less * Hemoglobin \>9.0 and \<12.0 g/dL * Must consume a minimum of 2 meals per day
Exclusion criteria
* Parathyroidectomy within 24 weeks of study * gastrointestinal bleed or inflammatory bowel disease within 12 weeks of study * Requirement for dialysis or kidney injury within 8 weeks of study * Absolute requirement for oral iron, intravenous iron, Erythropoiesis-Stimulating Agent, blood transfusions, and Sensipar during the study * Absolute requirement for calcium-, magnesium-, or aluminum-containing drugs with meals * Absolute requirement for vitamin C, niacin, or nicotinamide outside of multivitamins * History of hemochromatosis * Allergy to iron products * History of malignancy in last 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Transferrin Saturation (TSAT) From Baseline to End of Treatment | 12 Weeks | The difference in TSAT between the value at the end of treatment (week 12) minus the baseline measurement. |
| Change in Serum Phosphorus Levels From Baseline to End of Treatment | 12 Weeks | The difference in serum phosphorus between the value at the end of treatment (week 12) minus the baseline measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ferritin Levels From Baseline to End of Treatment | 12 Weeks | The difference in ferritin levels between the value at the end of treatment (week 12) minus the baseline measurement. |
| Change in Hemoglobin Levels From Baseline to End of Treatment | 12 Weeks | The difference in hemoglobin levels between the value at the end of treatment (week 12) minus the baseline measurement. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ferric Citrate Ferric citrate will be taken with or within one hour of meals or snacks. The dose of ferric citrate will depend on the patient's serum phosphorus results at each treatment visit.
Ferric Citrate: Dose depends on serum phosphorus levels collected at each study visit. | 75 |
| Placebo Placebo will be taken with or within one hour of meals or snacks. The number of placebo pills will depend on the patient's serum phosphorus results at each treatment visit.
Placebo | 73 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 |
| Overall Study | Lack of Efficacy | 1 | 11 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Not stated | 1 | 4 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | Ferric Citrate | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 44 Participants | 39 Participants | 83 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 34 Participants | 65 Participants |
| Age, Continuous | 65.8 years STANDARD_DEVIATION 12.15 | 64.5 years STANDARD_DEVIATION 13.55 | 65.1 years STANDARD_DEVIATION 12.83 |
| Chronic kidney disease (CKD), stage at baseline Other | 1 Participants | 1 Participants | 2 Participants |
| Chronic kidney disease (CKD), stage at baseline Stage III | 14 Participants | 16 Participants | 30 Participants |
| Chronic kidney disease (CKD), stage at baseline Stage IV | 39 Participants | 39 Participants | 78 Participants |
| Chronic kidney disease (CKD), stage at baseline Stage V | 21 Participants | 17 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 21 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 52 Participants | 112 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 16 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 59 Participants | 56 Participants | 115 Participants |
| Region of Enrollment United States | 75 Participants | 73 Participants | 148 Participants |
| Sex: Female, Male Female | 51 Participants | 45 Participants | 96 Participants |
| Sex: Female, Male Male | 24 Participants | 28 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 2 / 73 |
| other Total, other adverse events | 52 / 75 | 43 / 73 |
| serious Total, serious adverse events | 6 / 75 | 9 / 73 |
Outcome results
Primary
Change in Serum Phosphorus Levels From Baseline to End of Treatment
The difference in serum phosphorus between the value at the end of treatment (week 12) minus the baseline measurement.
Time frame: 12 Weeks
Population: The efficacy analyses were based on the ITT population. The Intent-to-Treat (ITT) population consisted of all subjects who were randomized into the study, had a baseline laboratory value, had taken at least 1 dose of study drug, and had at least 1 post-baseline laboratory value. ANCOVA with LOCF methodology was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferric Citrate | Change in Serum Phosphorus Levels From Baseline to End of Treatment | Baseline | 4.5 mg/dL | Standard Deviation 0.61 |
| Ferric Citrate | Change in Serum Phosphorus Levels From Baseline to End of Treatment | 12 weeks | 3.9 mg/dL | Standard Deviation 0.58 |
| Placebo | Change in Serum Phosphorus Levels From Baseline to End of Treatment | 12 weeks | 4.4 mg/dL | Standard Deviation 0.75 |
| Placebo | Change in Serum Phosphorus Levels From Baseline to End of Treatment | Baseline | 4.7 mg/dL | Standard Deviation 0.6 |
Primary
Change in Transferrin Saturation (TSAT) From Baseline to End of Treatment
The difference in TSAT between the value at the end of treatment (week 12) minus the baseline measurement.
Time frame: 12 Weeks
Population: Efficacy analyses were based on Intent-to-Treat (ITT) population, which consisted of all randomized subjects who had a baseline laboratory value, had taken at least 1 dose of study drug, \& had at least 1 post-baseline laboratory value. ANCOVA with Last observation carried forward (LOCF) methodology was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferric Citrate | Change in Transferrin Saturation (TSAT) From Baseline to End of Treatment | Baseline | 21.6 % saturation | Standard Deviation 7.44 |
| Ferric Citrate | Change in Transferrin Saturation (TSAT) From Baseline to End of Treatment | Week 12 | 31.7 % saturation | Standard Deviation 14.19 |
| Placebo | Change in Transferrin Saturation (TSAT) From Baseline to End of Treatment | Baseline | 21.0 % saturation | Standard Deviation 8.26 |
| Placebo | Change in Transferrin Saturation (TSAT) From Baseline to End of Treatment | Week 12 | 20.0 % saturation | Standard Deviation 7.55 |
Secondary
Change in Ferritin Levels From Baseline to End of Treatment
The difference in ferritin levels between the value at the end of treatment (week 12) minus the baseline measurement.
Time frame: 12 Weeks
Population: The efficacy analyses were based on the ITT population. The Intent-to-Treat (ITT) population consisted of all subjects who were randomized into the study, had a baseline laboratory value, had taken at least 1 dose of study drug, and had at least 1 post-baseline laboratory value. ANCOVA with LOCF methodology was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferric Citrate | Change in Ferritin Levels From Baseline to End of Treatment | Baseline | 115.8 ng/mL | Standard Deviation 83.11 |
| Ferric Citrate | Change in Ferritin Levels From Baseline to End of Treatment | Week 12 | 189.4 ng/mL | Standard Deviation 122.16 |
| Placebo | Change in Ferritin Levels From Baseline to End of Treatment | Baseline | 110.0 ng/mL | Standard Deviation 80.88 |
| Placebo | Change in Ferritin Levels From Baseline to End of Treatment | Week 12 | 105.6 ng/mL | Standard Deviation 93.87 |
Secondary
Change in Hemoglobin Levels From Baseline to End of Treatment
The difference in hemoglobin levels between the value at the end of treatment (week 12) minus the baseline measurement.
Time frame: 12 Weeks
Population: The efficacy analyses were based on the ITT population. The Intent-to-Treat (ITT) population consisted of all subjects who were randomized into the study, had a baseline laboratory value, had taken at least 1 dose of study drug, and had at least 1 post-baseline laboratory value. ANCOVA with LOCF methodology was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferric Citrate | Change in Hemoglobin Levels From Baseline to End of Treatment | Baseline | 10.5 g/dL | Standard Deviation 0.81 |
| Ferric Citrate | Change in Hemoglobin Levels From Baseline to End of Treatment | Week 12 | 11.0 g/dL | Standard Deviation 1.03 |
| Placebo | Change in Hemoglobin Levels From Baseline to End of Treatment | Baseline | 10.6 g/dL | Standard Deviation 1.07 |
| Placebo | Change in Hemoglobin Levels From Baseline to End of Treatment | Week 12 | 10.4 g/dL | Standard Deviation 1.14 |