This study evaluates the efficacy of PA21 in comparison with sevelamer carbonate (Renvela®) in lowering and maintaining serum phosphorus in adult Chinese subjects with CKD on dialysis after 12 weeks of treatment.
Primary Objective is to evaluate the efficacy of PA21 in comparison with sevelamer carbonate (Renvela®) in lowering and maintaining serum phosphorus in adult Chinese subjects with CKD on dialysis after 12 weeks of treatment. In addition , secondary objectives include evaluating the efficacy of PA21 and sevelamer carbonate over time as the percentage of subjects with serum phosphorus within the target range of 1.13 to 1.78 mmol/l (3.5 to 5.5 mg/dl) and to compare the safety and tolerability of PA21 versus sevelamer carbonate (Renvela®). In total, 286 patients (143 patients to PA21 treatment and 143 patients to sevelamer carbonate treatment) will be randomised with a screening period: up to 4 weeks and a washout period of up to 3 weeks. Treatment period (total duration 12 weeks) will include a dose titration period and a maintenance period of an open-label, active-controlled comparison of PA21 versus sevelamer carbonate for 4 weeks. The primary efficacy assessment will be a non-inferiority assessment of the 2 groups of subjects at Week 12 in terms of serum phosphate lowering capability. There will be a follow-up period of 30 days after last dosing. The investigational treatments will be a PA21 dose group of PA21 chewable tablets standardised to contain 500 mg of iron. PA21 contains approximately 20% m/m of elemental iron. All doses of PA21 are expressed in mg of iron. The Starting dose will be 1,500 mg/day (3 tablets/day (1 tablet per meal)). Dose increases or decreases of 500 mg/day (1 tablet/day) are permitted , provided a subject has been receiving that dose for a minimum of 2 weeks and for safety or tolerability reasons at any time. The maximum dose of PA21 will be 3,000 mg/day (6 x 500 mg tablets/day) and the minimum dose will be 1,000 mg/day (2 x 500 mg tablets/day). The active control is sevelamer carbonate, Renvela®, tablets, containing 800 mg of sevelamer carbonate. The starting dose will be 2.4 g/day (3 tablets/day). Dose increases or decreases of 2.4 g/day (3 tablets/day (1 tablet per meal)) are permitted, provided a subject has been receiving that dose for a minimum of 2 weeks, and for safety or tolerability reasons at any time. The maximum dose of sevelamer carbonate will be 14.4 g/day (18 tablets/day) and the minimum dose will be 2.4 g/day (3 tablets/day).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
286
sucroferric oxyhydroxide is a mixture of polynuclear iron(III)-oxyhydroxide (about 33% m/m), sucrose (about 30% m/m), and starches (about 28% m/m) and contains ≤10% m/m water.
sevelamer carbonate tablets containing 800 mg of sevelamer carbonate.
Southern Medical University Nanfang Hospital
Guangzhou, Guangdong, China
Serum phosphorus (mmol/l )
Change from baseline in serum phosphorus levels at Week 12: comparison between PA21 group and sevelamer carbonate group.
Time frame: baseline and 12 weeks
Serum phosphorus (mmol/l )
Serum phosphorus levels at each time point and change from baseline (BL)
Time frame: baseline, weeks 1, 2, 4, 6, 8, 12
Serum phosphorus (mmol/l)
% of subjects with serum phosphorus within 1.13 to 1.78 mmol/l
Time frame: baseline, weeks 1, 2, 4, 6, 8, 12
Adverse events (AEs)
Frequency of AEs determined by seriousness, severity and relatedness to study drugs
Time frame: baseline, weeks 1, 2, 4, 6, 8, 12
Diarrhoea.
Frequency of AE of special interest - diarrhoea.
Time frame: baseline, weeks 1, 2, 4, 6, 8, 12
Withdrawals due to AEs
Percentage of withdrawals due to AEs
Time frame: baseline, weeks 1, 2, 4, 6, 8, 12
Serum calcium (mmol/l)
Serum total calcium levels at each time point and change from baseline
Time frame: baseline, weeks 1, 2, 4, 6, 8, 12
Hypercalcemia (mmol/l)
Percentage of subjects that develop at least 1 episode of sustained hypercalcaemia (\>10.0 mg/dl; \>2.5 mmol/l) during study participation
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Time frame: baseline, weeks 1, 2, 4, 6, 8, 12
Serum iPTH (pg/ml)
Serum iPTH levels at specified time points and change from baseline
Time frame: baseline, weeks 8, 12
Serum iron (mcg/dl)
Serum iPTH levels at specified time points and change from baseline
Time frame: baseline, weeks 4, 8, 12
Serum ferritin (mcg/l)
Serum ferritin levels at specified time points and change from baseline
Time frame: baseline, weeks 4, 8, 12
Serum transferrin (mcg/dl)
Serum transferrin measured at specified timepoints
Time frame: baseline, weeks 4, 8, 12
Transferrin saturation (TSAT) (%)
TSAT measured at specified timepoints
Time frame: baseline, weeks 4, 8, 12