Six Month Phase 2A Trials
In two 6-month, Phase 2A 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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Twelve Month Phase 2B Trial
In a 12-month, Phase 2B clinical trial, Pyridorin™ demonstrated a significant reduction in the progression of overt diabetic nephropathy in patients with mild and moderate disease (baseline SCr between 1.3 and 3.0 mg/dL) that were on established standard of care at screening. Patients receiving a 300 mg BID dose showed a 57% treatment effect versus placebo (P=0.009; n=64). Patients receiving a 150 mg BID dose showed a 45% treatment effect (P=0.045; n=62).
Summary of Phase 2B trial design
- Placebo-controlled, multi-center, randomized, double-blinded
- Enrolled type 2 diabetics with macroalbuminuria (baseline PCR ≥ 1200 mg/g) and elevated serum creatinine (baseline SCr between 1.3 mg/dL and 3.7 mg/dL)
- Treatment period of 12 months
- Treatment was on top of standard of care
- All patients were on standard of care throughout the treatment period, i.e. adequate blood pressure control and a stable dose of antihypertensive medications in the class of angiotensin converting enzyme inhibitors (ACEi) or angiotensisn II receptor blockers (ARBs)
- Approximately 70% of patients were on previously established standard of care prior to initial screening
- Approximately 30% of patients required a run-in period to establish standard of care prior to randomization
- Enrolled 317 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™ 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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“"One out of every five healthcare dollars is spent caring for someone with diagnosed diabetes, while one in ten healthcare dollars is attributed to diabetes."
American Diabetes Association
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