Evaluation of TRC101 in Subjects With Chronic Kidney Disease and Metabolic Acidosis

A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Efficacy of TRC101 in Subjects With Chronic Kidney Disease and Low Serum Bicarbonate Levels

This was a double-blind, placebo-controlled, parallel-design, 6-arm, fixed dose study. The study enrolled 135 adult male and female subjects with Stage 3 or 4 chronic kidney disease and low serum bicarbonate levels. The study was conducted in two parts. In Part 1 study drug dosing (TRC101 or placebo) continued for 14 days twice daily (BID). In Part 2 study drug dosing (TRC101 or placebo) continued for 14 days once daily (QD).

The maximum study duration per subject was anticipated to be up to 42 days.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Investigative Site 1
• Georgia
  • Tbilisi, Georgia
    • Investigative Site 3
  • Tbilisi, Georgia
    • Investigative Site 4
  • Tbilisi, Georgia
    • Investigative Site 5
  • Tbilisi, Georgia
    • Investigative Site 6

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Estimated glomerular filtration rate (eGFR) of 20 to <60 mL/min/1.73m2
• Serum bicarbonate level of 12 to 20 mEq/L

Exclusion Criteria:

• Any level of low serum bicarbonate that, in the opinion of the Investigator, requires emergency intervention.
• Severe comorbid conditions other than chronic kidney disease.
• Chronic obstructive pulmonary disease.
• Anticipated changes in doses of any of the following drugs or drug classes: diuretics, non-ophthalmic carbonic anhydrase inhibitors, oral diabetes drugs, antihypertensive drugs, antacids, H2-blockers, or proton pump inhibitors.
• Excluded drugs or drug classes: insulin, non-daily or "as needed" diuretics, herbal products, dietary supplements, multivitamins, naturopathic remedies, sodium bicarbonate, potassium citrate, sodium citrate or other alkali therapy, non-steroidal anti-inflammatory drugs (NSAIDs), fiber supplements, laxatives, calcium and magnesium supplements, or electrolyte binders and other binder drugs.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo-BID; Administered twice daily (BID) for 14 days	Drug: Placebo; oral suspension
Experimental: TRC101 (1.5g BID); Administered twice daily (BID) for 14 days	Drug: TRC101; oral suspension; Other Names: Veverimer
Experimental: TRC101 (3g BID); Administered twice daily (BID) for 14 days	Drug: TRC101; oral suspension; Other Names: Veverimer
Experimental: TRC101 (4.5g BID); Administered twice daily (BID) for 14 days	Drug: TRC101; oral suspension; Other Names: Veverimer
Experimental: TRC101 (6g QD); Administered once daily (QD) for 14 days	Drug: TRC101; oral suspension; Other Names: Veverimer
Placebo Comparator: Placebo-QD; Administered once daily (QD) for 14 days	Drug: Placebo; oral suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Number of Subjects Who Discontinued Study Drug Due to a TEAE	The number and percentage of subjects who reported treatment-emergent adverse events (TEAEs) summarized by system organ class and preferred term (see Reported Adverse Events) as well as by severity, causality, seriousness, and action taken with regard to study drug. All analyses were descriptive.	Through treatment period completion (Day 15)
Change From Baseline to the End of Treatment (Day 15) in Serum Bicarbonate Within Each Individual TRC101 Dose Group	Serum bicarbonate at Day 15 minus serum bicarbonate at Baseline	Baseline and Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Change From Baseline in Serum Bicarbonate at Day 15 Between Each TRC101 Dose Group Versus Placebo	Serum bicarbonate at Day 15 minus serum bicarbonate at Baseline for each TRC101 dose group versus that for Placebo	Baseline and Day 15
Change From Baseline in Serum Bicarbonate at Day 15 Within the Combined TRC101 Treatment Group	Serum bicarbonate at Day 15 minus serum bicarbonate at Baseline	Baseline and Day 15
Comparison of Change From Baseline in Serum Bicarbonate at Day 15 Between the Combined TRC101 Treatment Group Versus Placebo	Serum bicarbonate at Day 15 minus serum bicarbonate at Baseline for the Combined TRC101 Treatment Group versus that for Placebo	Baseline and Day 15
Comparison of the Proportion of Subjects Whose Serum Bicarbonate Values Increased From Baseline to Day 15 by Greater Than or Equal to 2, 3, or 4 mEq/L Between Each TRC101 Dose Group Versus Placebo	Comparison of the proportion of subjects whose serum bicarbonate values increased from Baseline to Day 15 by greater than or equal to 2, 3, or 4 mEq/L between each TRC101 BID Dose Group versus Placebo	Baseline and Day 15
Change From Baseline in Serum Bicarbonate at Day 15 Within the TRC101 6g QD Dose Group	Serum bicarbonate at Day 15 minus serum bicarbonate at Baseline	Baseline and Day 15
Change From Baseline in Serum Bicarbonate at Day 15 Comparison Between the TRC101 6g QD Dose Group Versus Placebo	Serum bicarbonate at Day 15 minus serum bicarbonate at Baseline for the TRC101 6g dose group versus that for Placebo	Baseline and Day 15
Change From Baseline in Serum Bicarbonate at Day 15 Comparison Between the TRC101 6g QD Dose Group Versus the TRC101 3g BID Dose Group	Serum bicarbonate at Day 15 minus serum bicarbonate at Baseline for the TRC101 6g QD dose group versus that for the TRC101 3g BID dose group	Baseline and Day 15
Comparison of the Proportion of Subjects in the TRC101 6g QD Dose Group Whose Serum Bicarbonate Values Increased From Baseline to Day 15 by Greater Than or Equal to 2, 3, or 4 mEq/L Versus Placebo	Comparison of the proportion of subjects whose serum bicarbonate values increased from Baseline to Day 15 by greater than or equal to 2, 3, or 4 mEq/L between the 6g TRC101 QD Dose Group versus Placebo	Baseline and Day 15

Collaborators and Investigators

• Sponsor: Tricida, Inc.
• Investigators: Study Director: Yuri Stasiv, PhD, Tricida, Inc.

Publications and helpful links

General Publications

• Bushinsky DA, Hostetter T, Klaerner G, Stasiv Y, Lockey C, McNulty S, Lee A, Parsell D, Mathur V, Li E, Buysse J, Alpern R. Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD. Clin J Am Soc Nephrol. 2018 Jan 6;13(1):26-35. doi: 10.2215/CJN.07300717. Epub 2017 Nov 4. Erratum In: Clin J Am Soc Nephrol. 2019 Feb 7;14(2):277.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: June 14, 2016
• First Submitted That Met QC Criteria: June 17, 2016
• First Posted (Estimate): June 22, 2016

Study Record Updates

• Last Update Posted (Actual): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 2, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: kidney disease; serum bicarbonate; metabolic acidosis
• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Acid-Base Imbalance; Kidney Diseases; Renal Insufficiency, Chronic; Acidosis
• Other Study ID Numbers: TRCA-101; 2015-004327-31 (EudraCT Number)

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