Completed Phase 2 Trials
In two, previous, 6-month, Phase 2 clinical trials, Pyridorin™ demonstrated a significant reduction in the progression of overt diabetic nephropathy as measured by slowing the rate of increase of serum creatinine and the decline of glomerular filtration rate (GFR).
The following were common to both trials:
- Placebo-controlled, multi-center, randomized, double-blinded
- Enrolled type 1 and type 2 diabetics with macroalbuminuria and elevated serum creatinine
- Treatment period of 6 months
- Treatment was on top of standard of care
- Approximately 90% of the patients were taking antihypertensive medications in the class of angiotensin converting enzyme inhibitors (ACEi) or angiotensisn II receptor blockers (ARBs)
- Enrolled more than 200 diabetic nephropathy patients
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Confirmation of the improvement in the glomerular filtration rate (GFR) has come from examining the level of serum cystatin C, an endogenous biomarker that is an independent measure of GFR. This biomarker is:
- A low MW protease inhibitor found in all nucleated cells
- Freely filtered in glomerulus
- Completely catabolized in tubules
- Reflects earlier decline of GFR
- Is not secreted by tubules (unlike SCr)
- Is stable in stored frozen plasma
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Pyridorin™ therapy reduced the rate of increase in serum cystatin C (slope and change from baseline).
Summary of Human Efficacy Findings:
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Pyridorin™ significantly reduced the rate of increase in serum creatinine (slope and change from baseline)
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Pyridorin™ reduced the rate of increase in serum cystatin C (slope and change from baseline)
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Pyridorin™ significantly reduced urinary TGFβ1 levels, an important factor that promotes kidney scarring
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Pyridorin™ significantly reduced plasma AGE levels
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Pyridorin™'s beneficial effects were seen in patients who were already being treated with antihypertensive therapies, including ACEi and ARBs
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“"These Phase 2 clinical results have shown that the AGE blocker pyridoxamine is generally safe and well tolerated in patients with kidney disease due to diabetes mellitus. Retrospective analysis of these preliminary data suggest a potential effect to preserve the kidney function."
Am J Nephrol 2007;27:605–614
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