Effects of Pyridoxamine in Combined Phase 2 Studies of Patients with Type 1 and Type 2 Diabetes and Overt Nephropathy
| Autor: | Khalifah Rg, McGill Jb, Mark E. Williams, Schotzinger Rj, Degenhardt Tp, Warren K. Bolton |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Glycation End Products Advanced Male medicine.medical_specialty Adolescent Type 2 diabetes Disease Gastroenterology Diabetic nephropathy chemistry.chemical_compound Double-Blind Method Diabetes mellitus Internal medicine medicine Humans Diabetic Nephropathies In patient Aged business.industry Middle Aged Creatine medicine.disease Diabetes Mellitus Type 1 Treatment Outcome Overt nephropathy Endocrinology Diabetes Mellitus Type 2 chemistry Tolerability Nephrology Vitamin B Complex Kidney Failure Chronic Female Pyridoxamine business |
| Zdroj: | American Journal of Nephrology. 27:605-614 |
| ISSN: | 1421-9670 0250-8095 |
| Popis: | Background/Aims: Treatments of diabetic nephropathy (DN) delay the onset of end-stage renal disease. We report the results of safety/tolerability studies in patients with overt nephropathy and type 1/type 2 diabetes treated with pyridoxamine, a broad inhibitor of advanced glycation. Methods: The two 24-week studies were multicenter Phase 2 trials in patients under standard-of-care. In PYR-206, patients were randomized 1:1 and had baseline serum creatinine (bSCr) ≤2.0 mg/dl. In PYR-205/207, randomization was 2:1 and bSCr was ≤2.0 for PYR-205 and ≧2.0 but ≤3.5 mg/dl for PYR-207. Treated patients (122 active, 90 placebo) received 50 mg pyridoxamine twice daily in PYR-206; PYR-205/207 patients were escalated to 250 mg twice daily. Results: Adverse events were balanced between the groups (p = NS). Slight imbalances, mainly in the PYR-205/207 groups, were noted in deaths (from diverse causes, p = NS) and serious adverse events (p = 0.05) that were attributed to pre-existing conditions. In a merged data set, pyridoxamine significantly reduced the change from baseline in serum creatinine (p < 0.03). In patients similar to the RENAAL/IDNT studies (bSCr ≧1.3 mg/dl, type 2 diabetes), a treatment effect was observed on the rise in serum creatinine (p = 0.007). No differences in urinary albumin excretion were seen. Urinary TGF-β1 also tended to decrease with pyridoxamine (p = 0.049) as did the CML and CEL AGEs. Conclusion: These data provide a foundation for further evaluation of this AGE inhibitor in DN. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|