Long-term Safety Extension to Study TRCA-301

A Blinded, Placebo-Controlled Extension to Study TRCA-301 to Evaluate the Long-term Safety and Durability of Effect of TRC101 in Subjects With Chronic Kidney Disease and Metabolic Acidosis

This study is a 40-week, blinded, placebo-controlled extension of Study TRCA-301 (NCT03317444). Eligible subjects who complete the 12-week treatment period in Study TRCA-301 have the option to participate in this extension study evaluating the long-term safety and durability of effect of TRC101 in subjects with non-dialysis dependent chronic kidney disease and metabolic acidosis. Eligible subjects will be treated with TRC101 or placebo once daily (QD) on an out-patient basis for the subsequent 40 weeks. Subjects will continue to receive the same blinded treatment (TRC101 or placebo) that they received in Study TRCA-301.

Study Overview

• Status: Completed
• Conditions: Metabolic Acidosis
• Intervention / Treatment: Drug: Placebo; Drug: TRC101

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Investigative Site 11
• Georgia
  • Tbilisi, Georgia
    • Investigative Site 31
  • Tbilisi, Georgia
    • Investigative Site 32
  • Tbilisi, Georgia
    • Investigative Site 33
  • Tbilisi, Georgia
    • Investigative Site 34
  • Tbilisi, Georgia
    • Investigative Site 35
  • Tbilisi, Georgia
    • Investigative Site 36
  • Tbilisi, Georgia
    • Investigative Site 37
• Hungary
  • Budapest, Hungary
    • Investigative Site 41
  • Budapest, Hungary
    • Investigative Site 46
  • Hódmezővásárhely, Hungary
    • Investigative Site 49
  • Kistarcsa, Hungary
    • Investigative Site 44
• Serbia
  • Vršac, Serbia
    • Investigative Site 61
• Slovenia
  • Jesenice, Slovenia
    • Investigative Site 72
  • Maribor, Slovenia
    • Investigative Site 71
• Ukraine
  • Kharkiv, Ukraine
    • Investigative Site 81
  • Kharkiv, Ukraine
    • Investigative Site 83
  • Kharkiv, Ukraine
    • Investigative Site 87
  • Kharkiv, Ukraine
    • Investigative Site 88
  • Kyiv, Ukraine
    • Investigative Site 84
  • Kyiv, Ukraine
    • Investigative Site 85
  • Kyiv, Ukraine
    • Investigative Site 86
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Investigative Site 55
  • California
    • Los Angeles, California, United States, 90022
      • Investigative Site 91
  • Florida
    • Hialeah, Florida, United States, 33015
      • Investigative Site 59
    • Hollywood, Florida, United States, 33024
      • Investigative Site 93
    • Lauderdale Lakes, Florida, United States, 33313
      • Investigative Site 92
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Investigative Site 95
  • Texas
    • San Antonio, Texas, United States, 78215
      • Investigative Site 52

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Completed the 12-week treatment period and attended the Week 12 Visit in the parent study TRCA-301.
• Blood bicarbonate level of >= 12 mEq/L at the Week 12 Visit in the parent study TRCA-301.

Key Exclusion Criteria:

• Any level of low blood bicarbonate at the Week 12 Visit that, in the opinion of the Investigator, requires emergency intervention or evaluation for an acute acidotic process.
• Required dialysis for acute kidney injury or worsening CKD during the parent study TRCA-301.
• Planned initiation of renal replacement therapy within 6 months following study entry.
• History or current diagnosis of diabetic gastroparesis, bowel obstruction, swallowing disorders, severe gastrointestinal disorders, inflammatory bowel disease, major gastrointestinal surgery, or active gastric/duodenal ulcers.
• Serum calcium <= 8.0 mg/dL at the Week 10 in the parent study TRCA-301.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TRC101; Administered once daily (QD) for 40 weeks	Drug: TRC101; Oral suspension; Other Names: Veverimer
Placebo Comparator: Placebo; Administered once daily (QD) for 40 weeks	Drug: Placebo; Oral suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events, Serious Adverse Events, and Adverse Events Leading to Withdrawal.	The incidence of adverse events (AEs), serious adverse events (SAEs) and AEs leading to withdrawal. For incidence of AEs and SAEs, see Adverse Events Section. For incidence of AEs leading to withdrawal, see endpoint values below.	Week 12 Visit in the parent study, TRCA-301, to the Week 54 Visit in the extension study, TRCA-301E.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects With Change From Baseline in Serum Bicarbonate of ≥ 4 mEq/L or Serum Bicarbonate Within the Normal Range	Percent of subjects having a change from baseline in serum bicarbonate of at least 4 mEq/L or bicarbonate in the normal range (22 - 29 mEq/L) at the end of treatment (Week 52).	Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.
Change From Baseline in Serum Bicarbonate at the End of Treatment	Change from baseline in serum bicarbonate at the end of treatment (Week 52).	Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.
Change From Baseline in the Total Score of the KDQOL-PFD at the End of Treatment	Change from baseline in the total score of the Kidney Disease Quality of Life Physical Function Domain (KDQOL-PFD) at the end of treatment. The KDQOL is a validated, kidney disease-specific measure of health-related quality of life. For study TRCA-301E, and the parent study TRCA-301, the 10-question Item 3 of the KDQOL, also known as the SF-36 Physical Function subscale, was selected to measure physical functioning and is referenced herein as the KDQOL-PFD. The KDQOL-PFD was chosen as a patient-reported outcome measurement to evaluate the effects of TRC101 on daily activities that may be adversely affected by loss of muscle caused by metabolic acidosis. The minimum score for each of the 10 questions is 0 (physical activity highly limited) and the maximum is 100 (physical activity not limited). The total KDQOL-PFD score is calculated by adding the scores for all 10 questions, for a minimum and maximum possible total KDQOL-PFD score of 0 or 100, respectively.	Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.
Change From Baseline in the Duration of Repeated Chair Stand Test at the End of Treatment	Change from baseline in the duration of repeated chair stand test at the end of treatment (Week 52). The five-times repeated chair stand test was used as a measure of lower extremity muscle strength. In this test, the time it took for a subject to repeatedly stand from a chair five times was recorded. This test is among the group of measures (gait speed, chair stand, and balance tests) comprising the Short Physical Performance Battery (SPPB), which has been used as a predictive tool for possible disability and for monitoring physical functioning in older people.	Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.

Collaborators and Investigators

• Sponsor: Tricida, Inc.
• Investigators: Study Director: Clinical Operations, Tricida, Inc.

Publications and helpful links

General Publications

• Wesson DE, Mathur V, Tangri N, Stasiv Y, Parsell D, Li E, Klaerner G, Bushinsky DA. Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension. Lancet. 2019 Aug 3;394(10196):396-406. doi: 10.1016/S0140-6736(19)31388-1. Epub 2019 Jun 24.
• Mathur VS, Wesson DE, Tangri N, Li E, Bushinsky DA. Effects of veverimer on serum bicarbonate and physical function in women with chronic kidney disease and metabolic acidosis: a subgroup analysis from a randomised, controlled trial. BMC Nephrol. 2022 Feb 25;23(1):82. doi: 10.1186/s12882-022-02690-1.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2017
• Primary Completion (Actual): February 22, 2019
• Study Completion (Actual): February 22, 2019

Study Registration Dates

• First Submitted: December 28, 2017
• First Submitted That Met QC Criteria: December 28, 2017
• First Posted (Actual): January 4, 2018

Study Record Updates

• Last Update Posted (Actual): October 22, 2021
• Last Update Submitted That Met QC Criteria: September 24, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: blood bicarbonate, kidney disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Acidosis
• Other Study ID Numbers: TRCA-301E

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No