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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acidosis

Intervention / Treatment
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* Drug: Placebo
* Drug: TRC101


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metabolic acidosis, serum bicarbonate, kidney disease