Table 1.
Summary of clinical data from randomized trials for AST-120
| Reference | Approach | Patients | N | Treatment | Parameters | Results |
|---|---|---|---|---|---|---|
| Shoji et al23 | Open-label 12-month observation period followed by 12-month treatment period | Moderate CKD (baseline GFR 20–70 mL/minute; declined by ≥5 mL/minute during 12-month observation period) | 43 | Conventional treatment (diet + blood pressure management [n = 13]) AST-120 (6 g/day) + conventional treatment (n=l4) | Primary endpoint: mean change in GFR* | No significant difference between AST-120 versus conventional treatment for primary endpoint Mean change in GFR was significantly different following 12 months of treatment with AST-120 versus that observed in the same patients during the observation period |
| Nakamura et al24 | Chronic renal failure | 50 | Conventional treatment AST-120 (6 g/day) + conventional treatment | sCr, proteinuria, eGFR | After 12 months, AST-120 significantly inhibited the increase in sCr and significantly reduced proteinuria versus conventional treatment No significant difference in the decline in eGFR with AST-120 versus conventional treatment |
|
| Konishi et al25 | Open-label | Early-stage diabetic nephropathy | 16 | Conventional treatment AST-120 (6 g/day) + conventional treatment | sCr, urinary indoxyl sulfate | After 12 months, AST-120 significantly reduced sCr and urinary indoxyl sulfate levels versus conventional treatment alone |
| Akizawa et al26 | Randomized, controlled | CKD (baseline sCr < 5.0 mg/dL) | 460 | Conventional treatment AST-120 (6 g/day) + conventional treatment | Primary endpoint: doubling of sCr, increase in sCr to ≥6.0 mg/dL, ESRD†, or death | After 56 weeks, there was no difference between AST-120 and conventional treatment with regard to primary endpoint (42 versus 43 patients) eGFR declined significantly less with AST-120 versus conventional treatment Estimated CrCI decreased significantly less compared with baseline with AST-120 versus conventional therapy alone |
| Marier et al27 | Double-blind, placebo-controlled, cross-over 7 days treatment, 9 days washout | Mild stable CKD (baseline sCr 1.5–6.0 mg/dL) | 20 | Placebo + conventional treatment AST-120 (9 g/day) + conventional treatment | sCr, UcrV, CCr, URCL, safety | No significant differences were observed for sCr, UcrV, CCr, or URCL Most AEs were mild to moderate in severity and primarily GI-related. No patients discontinued due to AEs |
| Schulman et al28 | Double-blind, placebo-controlled 12-week treatment period | Moderate to severe CKD (baseline sCr 3.0–6.0 mg/dL) | 157 | Placebo + adequate protein-intake diet AST-120 (2.7, 6.3, 9.0 g/day) + adequate protein-intake diet | Primary endpoint: change in serum indoxyl sulfate level from baseline | Mean serum indoxyl sulfate levels decreased from baseline for the 9.0 and 6.3 g/day AST-120 treatment groups at week 12 |
Notes:
*
Directly measured by iothalamate clearance
†
need for hemodialysis or transplantation.
Abbreviations: AE, adverse event; CCr, creatinine clearance; CKD, chronic kidney disease; ESRD, end-stage renal disease; GFR, glomerular filtration rate; GI, gastrointestinal; sCr, serum creatinine; UcrV, 24-hour urinary creatinine; URCL, urea nitrogen clearance.