Rabeprazole use with vadadustat shows no change in pharmacokinetic exposure
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No clinically relevant changes were found with vadadustat pharmacokinetic exposure following co-administration of rabeprazole and vadadustat, according to a speaker at the virtual National Kidney Foundation Spring Clinical Meetings.
“When vadadustat was administered in combination with rabeprazole, there were no clinically relevant changes in the [maximum concentration of the drug achieved in the plasma] Cmax and [area under the curve] AUC values of vadadustat,” Rishikesh Sawant, director of clinical pharmacology at Akebia Therapeutics Inc., wrote in the abstract. Akebia is conducting clinical trials with vadadustat, a hypoxia-inducible factor stabilizer.
To determine if gastric acidity could alter the absorption of vadadustat, the effect of the acid-reducing agent rabeprazole was assessed on vadadustat pharmacokinetics. According to Sawant, the secondary objective of this study was to assess the safety and tolerability of vadadustat co-administered with rabeprazole.
In phase 1 of the fixed-sequence, open-label study, 19 adult patients (with BMIs between 18 kg/m2 and 30 kg/m2 with a minimum body weight of 45 kg for women and 50 kg for men) were recruited. Patients received a single oral dose of vadadustat (300 mg) on day 1, rabeprazole (20 mg) every 12 hours on days 2 through 5 and vadadustat plus rabeprazole on day 6.
Blood samples were collected prior to dosing and up to 48 hours post-dose for vadadustat pharmacokinetics evaluation on day 1 and day 6.
According to Sawant, the primary endpoints were vadadustat AUC from dosing to last quantifiable concentration, to infinity and maximum plasma concentration.
Results found exposure parameter values for vadadustat were similar after a single dose of vadadustat alone or vadadustat plus rabeprazole. No clinically relevant changes were found in the maximum concentration of the drug achieved in the plasma following dose administration and AUC values of vadadustat.
Most adverse events evaluated were mild in severity (92%) with headache (35%), constipation (15%), abdominal pain (10%) and nausea (10%) being the most frequently reported adverse events with vadadustat.
No serious adverse events were reported.
“Since administration of vadadustat after treatment with rabeprazole did not affect exposure of vadadustat, it is unlikely that other acid-reducing agents will affect vadadustat exposure due to changes in gastric pH,” Sawant wrote. – by Erin T. Welsh
Reference:
Sawant R. Abstract #194. Presented at: National Kidney Foundation Spring Clinical Meetings; March 26-29, 2020 (virtual meeting).
Disclosure: This study was funded by Akebia Therapeutics Inc.
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