Abstract: PO2116
No Adverse Effects of Veverimer on Volume Status or Blood Pressure in Patients with CKD and Metabolic Acidosis
Session Information
- CVD, BP, and Kidney Diseases: Exploring the Link
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1402 Hypertension and CVD: Clinical, Outcomes, and Trials
Authors
- Wesson, Donald E., Baylor Scott & White Health and Wellness Center, Dallas, Texas, United States
- Mathur, Vandana S., MathurConsulting, Woodside, California, United States
- Tangri, Navdeep, University of Manitoba, Winnipeg, Manitoba, Canada
- Stasiv, Yuri, Tricida, Inc., South San Francisco, California, United States
- Parsell, Dawn, 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
- Bushinsky, David A., University of Rochester Medical Center, Rochester, New York, United States
Background
Current American Heart Association guidelines recommend sodium (Na) restriction of <1.5 g/day. Drugs can be a source of Na, potentially contributing to inadequate control of blood pressure (BP) and volume. For example, each NaHCO3 tablet (650 mg) contains 170 mg of Na and multiple tablets per day are required to effectively treat metabolic acidosis.
Veverimer is a non-absorbed polymer that treats metabolic acidosis by binding and removing HCl from the GI tract. It is not an exchange resin and does not introduce unwanted cations such as Na or K. We hypothesized that veverimer would not increase BP, weight or induce volume overload. In Phase 3 randomized, blinded placebo-controlled trials in acidotic patients (pts) with CKD (baseline mean eGFR 29 mL/min/1.73 m2), veverimer significantly increased serum bicarbonate (LS mean +4.7 mEq/L at Week 52) with safety profile similar to placebo (Wesson et al. Lancet, 2019).
Methods
We analyzed parameters related to volume status in these Phase 3 trials.
Results
In these studies, 97% and 31% of pts, had HTN and CHF, respectively and 193 pts were treated with veverimer or placebo for up to 52 weeks. Treatment with veverimer (v placebo) had no effect on weight, BP, urine Na/creatinine ratio, volume-related adverse events, or increased use of diuretics or antihypertensives (Table).
Conclusion
Veverimer, a novel non-absorbed HCl binder, effectively treats metabolic acidosis in CKD without adversely affecting BP or volume status.
| Placebo (N = 81) | Veverimer (N = 112) | |
| Mean (SD) Change from Baseline to Week 52 | ||
| BP (systolic/diastolic, mmHg) | -2.0 (7.1)/-2.9 (5.8) | -2.0 (7.6)/-2.6 (8.0) |
| Body Weight (kg) | 0.5 (2.2) | -0.3 (2.7) |
| Urine Na/Creatinine (mol/mol) | 1.10 (10.35) | -0.08 (13.32) |
| Patients with Selected Adverse Events during 52-Week Study | ||
| Congestive Heart Failure | 4 (4%) | 3 (2%) |
| Hypertension | 4 (4%) | 7 (6%) |
| Peripheral Edema | 3 (3%) | 0 |
| Patients Starting Selected Medications during 52-Week Study | ||
| Diuretics | 8 (9%) | 8 (6%) |
| Antihypertensives | 5 (5%) | 9 (7%) |
Data presented are mean (SD) or n (%)
Funding
- Commercial Support –