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

Acidosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02809183
• Other study ID #: TRCA-101
• Secondary ID: 2015-004327-31
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2016
• Est. completion date: November 2016

Study information

• Verified date: January 2020
• Source: Tricida, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acidosis
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Placebo
oral suspension
• TRC101
oral suspension

Locations

Country	Name	City	State
Bulgaria	Investigative Site 1	Sofia
Georgia	Investigative Site 3	Tbilisi
Georgia	Investigative Site 4	Tbilisi
Georgia	Investigative Site 5	Tbilisi
Georgia	Investigative Site 6	Tbilisi

Sponsors (1)

Lead Sponsor	Collaborator
Tricida, Inc.

Countries where clinical trial is conducted

Bulgaria,  Georgia, 

References & Publications (1)

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): — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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