Metabolic Bone Disease
Conditions
Keywords
FGF23, CKD, Fosrenol, Hyperphosphatemia
Brief summary
The aim of the study is to assess the effects of the drug lanthanum carbonate (a phosphorus binder drug) on c-terminal and on FGF23 levels in patients with Chronic Kidney Disease (CKD). Targeting FGF23 measurement in CKD patients may impact both the progression of kidney disease and patient mortality.
Detailed description
This is a double blind randomized placebo controlled pilot study. Subjects with Chronic Kidney Disease ( CKD) stages 3-5 who are not undergoing renal replacement therapy and have not been started on phosphate binders will be randomized to either lanthanum carbonate 1500 mg daily or placebo for a 60 day treatment period. Patient doses will be increased up to a maximum dose of 3000 mg if the serum phosphate is greater than 5.5 mg/dL.
Interventions
DRUGLanthanum Carbonate (Fosrenol)
Randomization To either Lanthanum Carbonate 1 pill TID/Placebo 1 pill three times a day (TID) Day 15 If phosphorus is 3.5mg/dL-5.5mg/dL Continue with 1 pill TID. If phosphorus \<3.5mg/dL Reduce to 1 pill twice a day (BID). If Phosphorus \>5.5mg/dL 1 pill with breakfast 1 pill with lunch 2 pills with dinner Day 30 If phosphorus is 3.5mg/dL-5.5mg/dL Continue with 1 pill TID If phosphorus is \<3.5mg/dL Reduce to 1 pill daily. If phosphorus \>5.5mg/dL 1 pill with breakfast 2 pills with lunch 2 pills with dinner Day 45 If phosphorus is 3.5mg/dL-5.5mg/dL Continue with 1 pill TID If phosphorus \<3.5mg/dL stop the drug If phosphorus is \>5.5mg/dL 2 pills with breakfast 2 pills with lunch 2 pills with dinner
DRUGplacebo
Initial dose of placebo will be 1 pill three times a day
Sponsors
Shire
Endeavor Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and non-pregnant females ages 18 years of age or older * Estimated glomerular filtration rate (GFR) between 15-60 ml/min/1.73m * Serum phosphate \> 3.5 mg/dL * Fibroblast growth factor 2 (FGF2) \> 100 relative units per milliliter (RU/mL) * Corrected serum calcium \>8.0mg/dL
Exclusion criteria
* Current use of a phosphate binder * Corrected serum calcium \<8.0mg/dL * Current use of prescription-based vitamin D therapy * Acute kidney injury in last 3 months * Significant GI disorder * History of allergic reaction or sensitivity to lanthanum carbonate * History of non compliance with visits or medications that preclude study compliance in the opinion of the investigator * Pregnant or able to become pregnant and unwilling to use a birth control method considered reliable by the principal investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fibroblast Growth Factor (FGF) 23 Mean Change From Baseline | Baseline, 60 days | Mean change from baseline of FGF23 in subjects treated with Lanthanum Carbonate verse placebo at 60 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Phosphate Mean Change From Baseline | Baseline, 60 days | Mean change from baseline serum phosphate at 60 days |
| Change From Baseline Serum Parathyroid Hormone | Baseline, 60 days | Change from baseline serum parathyroid hormone at 60 days |
| 1,25 Dihydroxyvitamin D 3 Mean Change From Baseline | Baseline, 60 days | Mean change from baseline 1,25 dihydroxyvitamin D 3 at 60 days |
| Calcium Mean Change From Baseline | Baseline, 60 days | Mean change from baseline Calcium level at 60 days |
| Serum Alkaline Phosphatase Mean Change From Baseline | Baseline, 60 days | Mean change from baseline serum alkaline phosphatase at 60 days |
| Serum Osteocalcin Mean Change From Baseline | Baseline, 60 days | Mean change from baseline serum osteocalcin at 60 days |
| 24 Hour Urine Phosphate Mean Change From Baseline | Baseline, 60 days | Mean change from baseline 24 hour urine phosphate at 60 days |
| 25 Hydroxyvitamin D Mean Change From Baseline | Baseline, 60 days | Mean change from baseline 25 hydroxyvitamin D at 60 days |
Countries
United States
Participant flow
Recruitment details
The date of recruitment 10/27/09-3/7/12.The subjects were seen at Evanston and Glenbrook outpatient clinics
Pre-assignment details
Subjects who were naive to phosphate binders were enrolled
Participants by arm
| Arm | Count |
|---|---|
| Lanthanum Carbonate (Fosrenol) Subjects will receive the study drug Lanthanum Carbonate ( Fosrenol)
Lanthanum Carbonate (Fosrenol): Randomization To either Lanthanum Carbonate 1 pill TID/Placebo 1 pill TID Day 15 If phosphorus is 3.5mg/dL-5.5mg/dL Continue with 1 pill TID. If phosphorus \<3.5mg/dL Reduce to 1 pill BID. If Phosphorus \>5.5mg/dL 1 pill with breakfast 1 pill with lunch 2 pills with dinner Day 30 If phosphorus is 3.5mg/dL-5.5mg/dL Continue with 1 pill TID If phosphorus is \<3.5mg/dL Reduce to 1 pill daily. If phosphorus \>5.5mg/dL 1 pill with breakfast 2 pills with lunch 2 pills with dinner Day 45 If phosphorus is 3.5mg/dL-5.5mg/dL Continue with 1 pill TID If phosphorus \<3.5mg/dL stop the drug If phosphorus is \>5.5mg/dL 2 pills with breakfast 2 pills with lunch 2 pills with dinner | 10 |
| Placebo Subject will receive placebo
placebo: Initial dose of placebo will be 1 pill three times a day | 9 |
| Total | 19 |
Baseline characteristics
| Characteristic | Lanthanum Carbonate (Fosrenol) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 4 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Region of Enrollment United States | 10 participants | 9 participants | 19 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 |
| other Total, other adverse events | 1 / 10 | 0 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 |
Outcome results
Primary
Fibroblast Growth Factor (FGF) 23 Mean Change From Baseline
Mean change from baseline of FGF23 in subjects treated with Lanthanum Carbonate verse placebo at 60 days
Time frame: Baseline, 60 days
Population: Only patients with readings at both timepoints (baseline and 60 days) were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanthanum Carbonate (Fosrenol) | Fibroblast Growth Factor (FGF) 23 Mean Change From Baseline | -62.96 RU/mL | Standard Deviation 55.17 |
| Placebo | Fibroblast Growth Factor (FGF) 23 Mean Change From Baseline | 9.08 RU/mL | Standard Deviation 53.84 |
p-value: 0.037t-test, 2 sided
Secondary
1,25 Dihydroxyvitamin D 3 Mean Change From Baseline
Mean change from baseline 1,25 dihydroxyvitamin D 3 at 60 days
Time frame: Baseline, 60 days
Population: Only patients with readings at both timepoints (baseline and 60 days) were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanthanum Carbonate (Fosrenol) | 1,25 Dihydroxyvitamin D 3 Mean Change From Baseline | -1.25 ng/mL | Standard Deviation 8.66 |
| Placebo | 1,25 Dihydroxyvitamin D 3 Mean Change From Baseline | -12.20 ng/mL | Standard Deviation 23.83 |
p-value: 0.416t-test, 2 sided
Secondary
24 Hour Urine Phosphate Mean Change From Baseline
Mean change from baseline 24 hour urine phosphate at 60 days
Time frame: Baseline, 60 days
Population: Only patients with readings at both timepoints (baseline and 60 days) were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanthanum Carbonate (Fosrenol) | 24 Hour Urine Phosphate Mean Change From Baseline | -148.6 mg | Standard Deviation 64.3 |
| Placebo | 24 Hour Urine Phosphate Mean Change From Baseline | 5.2 mg | Standard Deviation 78.7 |
p-value: 0.0066t-test, 2 sided
Secondary
25 Hydroxyvitamin D Mean Change From Baseline
Mean change from baseline 25 hydroxyvitamin D at 60 days
Time frame: Baseline, 60 days
Population: Only patients with readings at both timepoints (baseline and 60 days) were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanthanum Carbonate (Fosrenol) | 25 Hydroxyvitamin D Mean Change From Baseline | 0.43 ng/mL | Standard Deviation 6.16 |
| Placebo | 25 Hydroxyvitamin D Mean Change From Baseline | 2.00 ng/mL | Standard Deviation 7.67 |
p-value: 0.672t-test, 2 sided
Secondary
Calcium Mean Change From Baseline
Mean change from baseline Calcium level at 60 days
Time frame: Baseline, 60 days
Population: Only patients with readings at both timepoints (baseline and 60 days) were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanthanum Carbonate (Fosrenol) | Calcium Mean Change From Baseline | 0.15 mg/dL | Standard Deviation 0.49 |
| Placebo | Calcium Mean Change From Baseline | 0.04 mg/dL | Standard Deviation 0.72 |
p-value: 0.721t-test, 2 sided
Secondary
Change From Baseline Serum Parathyroid Hormone
Change from baseline serum parathyroid hormone at 60 days
Time frame: Baseline, 60 days
Population: Only patients with readings at both timepoints (baseline and 60 days) were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanthanum Carbonate (Fosrenol) | Change From Baseline Serum Parathyroid Hormone | -18.75 percent change in PTH | Standard Deviation 25.91 |
| Placebo | Change From Baseline Serum Parathyroid Hormone | -33.25 percent change in PTH | Standard Deviation 117.7 |
p-value: 0.743t-test, 2 sided
Secondary
Serum Alkaline Phosphatase Mean Change From Baseline
Mean change from baseline serum alkaline phosphatase at 60 days
Time frame: Baseline, 60 days
Population: Only patients with readings at both timepoints (baseline and 60 days) were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanthanum Carbonate (Fosrenol) | Serum Alkaline Phosphatase Mean Change From Baseline | -0.50 U/L | Standard Deviation 4.51 |
| Placebo | Serum Alkaline Phosphatase Mean Change From Baseline | -0.40 U/L | Standard Deviation 1.91 |
p-value: 0.955t-test, 2 sided
Secondary
Serum Osteocalcin Mean Change From Baseline
Mean change from baseline serum osteocalcin at 60 days
Time frame: Baseline, 60 days
Population: Osteocalcin concentrations were not measured
p-value: <0.05t-test, 2 sided
Secondary
Serum Phosphate Mean Change From Baseline
Mean change from baseline serum phosphate at 60 days
Time frame: Baseline, 60 days
Population: Only patients with readings at both timepoints (baseline and 60 days) were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanthanum Carbonate (Fosrenol) | Serum Phosphate Mean Change From Baseline | 0.18 mg/dL | Standard Deviation 0.93 |
| Placebo | Serum Phosphate Mean Change From Baseline | 0.22 mg/dL | Standard Deviation 0.54 |
p-value: 0.897t-test, 2 sided