Abstract: PO2374
Action of Veverimer on Gastrointestinal Acid Binding Is Not Affected by Omeprazole
Session Information
- Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Parsell, Dawn, Tricida, Inc., South San Francisco, California, United States
- Guttendorf, Robert, Aclairo Pharmaceutical Development Group, Vienna, Virginia, United States
- Stasiv, Yuri, Tricida, Inc., South San Francisco, California, United States
- Li, Elizabeth, PharmaStat LLC, Fremont, California, United States
- Klaerner, Gerrit, Tricida, Inc., South San Francisco, California, United States
- Mathur, Vandana S., MathurConsulting, Woodside, California, United States
Background
Veverimer, an orally administered, non-absorbed polymer that selectively binds and removes hydrochloric acid (HCl) from the gastrointestinal tract, has been shown to correct metabolic acidosis in patients with CKD. Unlike proton pump inhibitors (PPIs), which do not affect systemic acid-base status, the removal of HCl from the gastrointestinal tract by veverimer leads to a net increase in blood bicarbonate. Veverimer was designed to bind HCl across a wide range of intraluminal pH, but the effect of veverimer on acid binding in the presence of PPIs has not been previously described.
Methods
To evaluate the effect of veverimer on gastric pH, we conducted a Phase 1, open-label, 2-stage study in which subjects (N=46) were randomized 1:1:1:1 to receive 1 of 4 study drug treatments (water fasted; water fed; veverimer fasted; veverimer fed) in the presence and absence of a steady-state level of omeprazole. Gastric pH was measured continuously for 22 hours (hrs) using a microelectrode pH probe positioned in the gastric fundus.
Results
Ingestion of veverimer caused a modest, transient increase in gastric pH that peaked within 1 hr post-dose. In the absence and presence of food, the median (distribution-free 95% CI) times to peak pH after veverimer administration was 0.25 (0.17, 1.00) and 0.71 (0.25, 1.17) hrs, respectively. Peak pH after veverimer administration was ~3 and ~1.5 pH units greater than that observed after water control in the fasted and fed states, respectively. The magnitudes of these increases were in the same range in the presence of omeprazole. Gastric pH returned to baseline after ~1.5 hrs under fasting conditions and after ~3 hrs under fed conditions. In the presence of omeprazole, the veverimer-induced gastric pH increase dissipated by 4 hrs post-dose or shortly after initiation of the subsequent meal.
Conclusion
The effect of veverimer on gastric pH is transient and similar in the presence or absence of omeprazole. The magnitude of the individual effects of food, veverimer, and omeprazole on gastric pH were similar (increase of 2–4 pH units). These findings are consistent with prior studies in patients with CKD in which the magnitude of efficacy of veverimer was unaffected by use of H2-receptor antagonists and PPIs (Wesson et al. Lancet, 2019).
Funding
- Commercial Support –