Hyperphosphatemia, Chronic Kidney Disease
Conditions
Keywords
hyperphosphatemia, hemodialysis, chitosan
Brief summary
This was a study to evaluate the efficacy and safety of HS219, chitosan-loaded chewing gum, when given three times a day for 3 weeks to the hemodialysis (HD) patients with hyperphosphatemia whose serum inorganic phosphorus was not well controlled with calcium carbonate or sevelamer hydrogen chloride.
Interventions
DIETARY_SUPPLEMENTHS219
Chewing for 30 min three time a day far after meal
DIETARY_SUPPLEMENTPlacebo
Chewing for 30 min three times a day far after meal
Sponsors
KDL Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent given * Able to comply with the study procedures and medication * On a stable HD regimen (at least 3 x per week) for ≥ 3 months * Subject receiving calcium carbonate or sevelamer hydrochloride as a phosphate binder at screening, must have been on a stable regimen (dose and medication) for at least 1 month * A mean serum inorganic phosphorous in the previous 3 tests : \> 5.5 mg/dL and \< 9.0 mg/dL * Removal rate of blood urea nitrogen (BUN) ≥ 60% * Rate of salivary flow by Saxon test ≥ 1 g/2 min
Exclusion criteria
* Blood purification therapy other than HD * Current clinically significant intestinal motility disorder * Possible parathyroid intervention during the study period * History of malignancy and severe cardiovascular disorders such as heart disease, angina, congested heart failure, valve stenosis, atrial fibrillation and arrhythmia * History of allergy against active ingredient * Receipt of any investigational drug within 30 days of informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Inorganic Phosphorus at the End of Treatment From Baseline | baseline and end of the chewing treatment during three week treatment period | Change in serum inorganic phosphorus at the end of treatment from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Intact Parathyroid Hormone (PTH) Level | week 3 | Serum intact and whole PTH levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday). |
| Number of Participants With Serum Inorganic Phosphorus Reduction of 1.5 mg/dL | baseline and end of the treatment | — |
| Achievement Number of Participants With Serum Inorganic Phosphorus; 3.5 ≦P<5.5 mg/dL at Week 3 | week 3 | — |
| Ca×P | week 3 | Serum inorganic phosphorus and Ca levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday). |
| Salivary Inorganic Phosphorus Level | week 3 | Salivary inorganic phosphorus levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday). |
| Corrected Serum Calcium (Ca) Level Based on the Serum Albumin Level Corrected Serum Calcium (mg/dL) = Measured Total Ca (mg/dL) + (4 - Serum Albumin [g/dL]) | week 3 | Serum Ca levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday). |
| Serum Intact Fibroblast Growth Factor (FGF) 23 Level | week 3 | Serum intact FGF23 levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday). |
| Serum Inorganic Phosphorus Level | week 3 | Serum inorganic phosphorus levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday). |
Countries
Japan
Participant flow
Pre-assignment details
Sixty eight HD patients maintained on calcium carbonate (33 subjects) or sevelamer (35 subjects) were enrolled during January - April, 2010. Sixty-three patients chewed at least one gum: 35 HS219 and 28 placebo.
Participants by arm
| Arm | Count |
|---|---|
| HS219 Participants chewed HS219 chewing gum three times a day while fasting (i.e., between meals) for 30 min for 3 weeks. | 35 |
| Placebo Participants chewed placebo chewing gum three times a day while fasting (i.e., between meals) for 30 min for 3 weeks. | 28 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | HS219 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 57.1 years STANDARD_DEVIATION 11 | 55.7 years STANDARD_DEVIATION 11.3 | 56.4 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 24 Participants | 19 Participants | 43 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 35 | 12 / 28 |
| serious Total, serious adverse events | 0 / 35 | 0 / 28 |
Outcome results
Primary
Change in Serum Inorganic Phosphorus at the End of Treatment From Baseline
Change in serum inorganic phosphorus at the end of treatment from baseline
Time frame: baseline and end of the chewing treatment during three week treatment period
Population: Full Analysis Set included all randomized participants who received at least one dose of study product. The endpoint was analyzed only for those participants who had data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS219 | Change in Serum Inorganic Phosphorus at the End of Treatment From Baseline | -0.26 mg/dL | Standard Deviation 1.19 |
| Placebo | Change in Serum Inorganic Phosphorus at the End of Treatment From Baseline | -0.20 mg/dL | Standard Deviation 1.21 |
Secondary
Achievement Number of Participants With Serum Inorganic Phosphorus; 3.5 ≦P<5.5 mg/dL at Week 3
Time frame: week 3
Population: Per Protocol Set included randomized participants who completed the entire clinical trial and were counted towards the final results. The endpoint was analyzed only for those participants who had data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HS219 | Achievement Number of Participants With Serum Inorganic Phosphorus; 3.5 ≦P<5.5 mg/dL at Week 3 | 8 participants |
| Placebo | Achievement Number of Participants With Serum Inorganic Phosphorus; 3.5 ≦P<5.5 mg/dL at Week 3 | 2 participants |
Secondary
Ca×P
Serum inorganic phosphorus and Ca levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday).
Time frame: week 3
Population: Per Protocol Set included randomized participants who completed the entire clinical trial and were counted towards the final results. The endpoint was analyzed only for those participants who had data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS219 | Ca×P | 59.90 mg/mL*mg/mL | Standard Deviation 13.87 |
| Placebo | Ca×P | 57.24 mg/mL*mg/mL | Standard Deviation 11.34 |
Secondary
Corrected Serum Calcium (Ca) Level Based on the Serum Albumin Level Corrected Serum Calcium (mg/dL) = Measured Total Ca (mg/dL) + (4 - Serum Albumin [g/dL])
Serum Ca levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday).
Time frame: week 3
Population: Per Protocol Set included randomized participants who completed the entire clinical trial and were counted towards the final results. The endpoint was analyzed only for those participants who had data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS219 | Corrected Serum Calcium (Ca) Level Based on the Serum Albumin Level Corrected Serum Calcium (mg/dL) = Measured Total Ca (mg/dL) + (4 - Serum Albumin [g/dL]) | 9.37 mg/dL | Standard Deviation 0.66 |
| Placebo | Corrected Serum Calcium (Ca) Level Based on the Serum Albumin Level Corrected Serum Calcium (mg/dL) = Measured Total Ca (mg/dL) + (4 - Serum Albumin [g/dL]) | 9.13 mg/dL | Standard Deviation 0.61 |
Secondary
Number of Participants With Serum Inorganic Phosphorus Reduction of 1.5 mg/dL
Time frame: baseline and end of the treatment
Population: Full Analysis Set included all randomized participants who received at least one dose of study product. The endpoint was analyzed only for those participants who had data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HS219 | Number of Participants With Serum Inorganic Phosphorus Reduction of 1.5 mg/dL | 7 participants |
| Placebo | Number of Participants With Serum Inorganic Phosphorus Reduction of 1.5 mg/dL | 2 participants |
Secondary
Salivary Inorganic Phosphorus Level
Salivary inorganic phosphorus levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday).
Time frame: week 3
Population: Per Protocol Set included randomized participants who completed the entire clinical trial and were counted towards the final results. The endpoint was analyzed only for those participants who had data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS219 | Salivary Inorganic Phosphorus Level | 22.32 mg/dL | Standard Deviation 8.04 |
| Placebo | Salivary Inorganic Phosphorus Level | 21.51 mg/dL | Standard Deviation 8.95 |
Secondary
Serum Inorganic Phosphorus Level
Serum inorganic phosphorus levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday).
Time frame: week 3
Population: Per Protocol Set included randomized participants who completed the entire clinical trial and were counted towards the final results. The endpoint was analyzed only for those participants who had data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS219 | Serum Inorganic Phosphorus Level | 6.38 mg/dL | Standard Deviation 1.35 |
| Placebo | Serum Inorganic Phosphorus Level | 6.29 mg/dL | Standard Deviation 1.29 |
Secondary
Serum Intact Fibroblast Growth Factor (FGF) 23 Level
Serum intact FGF23 levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday).
Time frame: week 3
Population: Per Protocol Set included randomized participants who completed the entire clinical trial and were counted towards the final results. The endpoint was analyzed only for those participants who had data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS219 | Serum Intact Fibroblast Growth Factor (FGF) 23 Level | 4.0 log10(pg/mL) | Standard Deviation 0.5 |
| Placebo | Serum Intact Fibroblast Growth Factor (FGF) 23 Level | 4.0 log10(pg/mL) | Standard Deviation 0.5 |
Secondary
Serum Intact Parathyroid Hormone (PTH) Level
Serum intact and whole PTH levels were determined at week 3 before the first dialysis of the week (Monday or Tuesday).
Time frame: week 3
Population: Per Protocol Set included randomized participants who completed the entire clinical trial and were counted towards the final results. The endpoint was analyzed only for those participants who had data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HS219 | Serum Intact Parathyroid Hormone (PTH) Level | 206.5 pg/mL | Standard Deviation 141.2 |
| Placebo | Serum Intact Parathyroid Hormone (PTH) Level | 251.2 pg/mL | Standard Deviation 183.6 |