Novel xanthine oxidase/URAT1 may cause acute kidney injury
With rise in research and development, there has been addition of several new xanthine oxidase (XO) inhibitors. But before including these novel drugs in treatment plan, it is important to study their safety and efficacy.
Recently, a phase 1 clinical study has been conducted to evaluate the safety and urate lowering activity of a novel urate transporter 1 (URAT1)/ xanthine oxidase (XO) inhibitor PF-06743649 in patients with gout. Increasing doses of PF-06743649 or placebo were given to gout patients and healthy (young and elderly) patients.
Examination included serum uric acid (sUA) and urinary pharmacodynamic markers. Safety was evaluated by assembling adverse events, safety labs, ECG’s and vital signs. There was rapid decrease in sUA for all groups of patients. Change of 69% from the baseline was reported with 40 mg dose. All other biomarkers were found to be constant with inhibition of both URAT1 and XO.
While dosing was accepted well by the groups, two patients experienced serious adverse events of acute kidney injury. They were hospitalized due to increase in the serum creatinine and blood urea nitrogen in first 3 days after first dose. One patient exhibited oliguria for the first 24 h. Complete recovery was seen in both patients with nominal treatment. Due to an identified renal safety risk, further development was stopped.
The findings suggest that PF-06743649 is definitely effective at rapidly lowering sUA, but must be used cautiously in gout patients as it carries risk of renal injuries.