End-Stage Renal Disease, Hyperphosphatemia
Conditions
Keywords
Hyperphosphatemia, ESRD, Dialysis, End Stage Renal Disease, Phosphorus, Renal, Kidney
Brief summary
This is a research study for people with high blood phosphorus levels who are on dialysis. This medical condition can cause weakening of the bones and damage other organs. This can lead to many health problems, and sometimes death. Phosphorus is in much of the food we eat, and is helpful to us in small amounts. Patients with kidney failure have trouble getting rid of the phosphorus eaten in food. Dialysis can help remove some of the phosphorus, but often patients must take a phosphate binder like PhosLo®, Renagel®, or Renvela® to bring the blood phosphorus levels back to normal. The purpose of this study is to see if KRX-0502 (ferric citrate) is safe and effective as a phosphate binder.
Detailed description
There will be a screening visit about 4 weeks receiving study drug. Upon qualifying for the study after the screening visit, patients will then be asked to stop taking their current phosphate binder for about 2 weeks. Then, if patients continue to qualify for the study, they will be entered in the study that lasts about 28 days. Study visits will happen every week during the patient's usual dialysis appointments. There will be a total of up to 9 visits for this study, and total participation time could last up to 8 weeks.
Interventions
DRUGferric citrate
1, 6, or 8 g/day taken within 1 hour of meals or snacks daily for 28 days
Sponsors
Collaborative Study Group (CSG)
Keryx Biopharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or non-pregnant, non-lactating females * Age \> 18 years * On thrice weekly hemodialysis or peritoneal dialysis for at least the previous three months prior to Screening Visit (Visit 0) * Serum phosphorus levels ≥ 3.5 mg/dL and \< 8.0 mg/dL at Screening Visit (Visit 0) * Serum phosphorus levels \> 6.0 mg/dL during the washout period (Visits 2 or 3) * Taking 3 to 15 tablets/capsules per day of 667mg calcium acetate or 800 mg sevelamer (hydrochloride or carbonate), or any combination of these agents as reported by the patient at Screening Visit (Visit 0) * Serum ferritin \<1000micrograms/L and Transferrin Saturation (TSAT) \<50% at the Screening Visit (Visit 0) * Willingness to be discontinued from current phosphate binder(s) and initiated on KRX-0502 (ferric citrate) * Willing and able to give informed consent * Willing and able to stay on a constant dose of Vitamin D (or its analogs) and Sensipar (cinacalcet) for the treatment period, if applicable.
Exclusion criteria
* Parathyroidectomy within six months prior to Screening Visit (Visit 0) * Actively symptomatic gastrointestinal bleeding or inflammatory bowel disease * Serum phosphorus levels \>10.0 mg/dL documented in all of the three monthly laboratories (done routinely in the dialysis unit) in the three months prior to the Screening Visit (Visit 0) * History of multiple drug allergies or intolerances * History of malignancy in the last five years (treated cervical or non-melanomatous skin cancer may be permitted if approved by CCC) * Previous intolerance to oral ferric citrate * Absolute requirement for oral iron therapy * Absolute requirement for Vitamin C (multivitamins \[Nephrocaps, Renaphro, etc.\] allowed) * Absolute requirement for calcium-, magnesium-, or aluminum-containing drugs with meals * Psychiatric disorder that interferes with the patient's ability to comply with the study protocol * Inability to tolerate oral drug intake * Planned surgery or hospitalization during the trial (scheduled outpatient access surgery allowed) * Any other medical condition that renders the patient unable to or unlikely to complete the trial or that would interfere with optimal participation in the trial or produce significant risk to the patient * Receipt of any investigational drug within 30 days of Screening Visit (Visit 0) * Inability to cooperate with study personnel or history of noncompliance * Unsuitable for this trial per Principal Investigator's clinical judgment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Phosphorus From Baseline to End of Treatment | Baseline and day 28 | Mean change from baseline was calculated separately for each treatment arm (LOCF) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pairwise Comparison of the Mean Change in Serum Phosphorus From Baseline to the End of Treatment | Baseline and day 28 | Mean change from baseline was calculated separately for each treatment arm. Only subjects that have both baseline and end of treatment serum phosphorus scores were analyzed for this outcome. |
| Proportion of Patient With a Serum Phosphorus ≤5.5 mg/dL at the End of Treatment | Baseline and day 28 | proportion was calculated separately for each treatment arm |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
3 patients were randomized, but withdrew before initiating study treatment
Participants by arm
| Arm | Count |
|---|---|
| 1 g/Day 1 g/day KRX-0502 (ferric citrate) taken within 1 hour of meals or snacks daily for 28 days | 50 |
| 6 g/Day 6 g/day KRX-0502 (ferric citrate) taken within 1 hour of meals or snacks daily for 28 days | 51 |
| 8 g/Day 8 g/day KRX-0502 (ferric citrate) taken within 1 hour of meals or snacks daily for 28 days | 45 |
| Total | 146 |
Baseline characteristics
| Characteristic | 1 g/Day | 6 g/Day | 8 g/Day | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 14 Participants | 6 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 37 Participants | 39 Participants | 115 Participants |
| Region of Enrollment Puerto Rico | 3 participants | 2 participants | 3 participants | 8 participants |
| Region of Enrollment United States | 47 participants | 49 participants | 42 participants | 138 participants |
| Sex: Female, Male Female | 18 Participants | 21 Participants | 19 Participants | 58 Participants |
| Sex: Female, Male Male | 32 Participants | 30 Participants | 26 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 34 / 51 | 43 / 52 | 41 / 48 |
| serious Total, serious adverse events | 6 / 51 | 7 / 52 | 9 / 48 |
Outcome results
Primary
Change in Serum Phosphorus From Baseline to End of Treatment
Mean change from baseline was calculated separately for each treatment arm (LOCF)
Time frame: Baseline and day 28
Population: Intent to Treat (ITT) Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1 g/Day | Change in Serum Phosphorus From Baseline to End of Treatment | -0.10 mg/dL | Standard Deviation 1.285 |
| 6 g/Day | Change in Serum Phosphorus From Baseline to End of Treatment | -1.86 mg/dL | Standard Deviation 1.692 |
| 8 g/Day | Change in Serum Phosphorus From Baseline to End of Treatment | -2.13 mg/dL | Standard Deviation 1.998 |
Comparison: To assess dose ranging, the primary efficacy variable will be analyzed via a model with dose effect. Positive dose ranging confirmed if the null hypothesis of slope =0 was rejected at a significance level of 0.05p-value: <0.0001Regression, Linear
Secondary
Pairwise Comparison of the Mean Change in Serum Phosphorus From Baseline to the End of Treatment
Mean change from baseline was calculated separately for each treatment arm. Only subjects that have both baseline and end of treatment serum phosphorus scores were analyzed for this outcome.
Time frame: Baseline and day 28
Population: Intent-to-Treat, includes only subjects that had both baseline and end of study actual values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1 g/Day | Pairwise Comparison of the Mean Change in Serum Phosphorus From Baseline to the End of Treatment | 0.04 mg/dL | Standard Deviation 1.32 |
| 6 g/Day | Pairwise Comparison of the Mean Change in Serum Phosphorus From Baseline to the End of Treatment | -1.94 mg/dL | Standard Deviation 1.813 |
| 8 g/Day | Pairwise Comparison of the Mean Change in Serum Phosphorus From Baseline to the End of Treatment | -2.21 mg/dL | Standard Deviation 2.097 |
Secondary
Proportion of Patient With a Serum Phosphorus ≤5.5 mg/dL at the End of Treatment
proportion was calculated separately for each treatment arm
Time frame: Baseline and day 28
Population: Intent-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 g/Day | Proportion of Patient With a Serum Phosphorus ≤5.5 mg/dL at the End of Treatment | 12.0 % of Participants |
| 6 g/Day | Proportion of Patient With a Serum Phosphorus ≤5.5 mg/dL at the End of Treatment | 51.0 % of Participants |
| 8 g/Day | Proportion of Patient With a Serum Phosphorus ≤5.5 mg/dL at the End of Treatment | 57.8 % of Participants |