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

Study Overview
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Brief Summary
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This is a multicenter, double-blind, placebo-controlled, parallel-design study. The study will enroll approximately 210 adult male and female subjects with stage 3 or 4 chronic kidney disease and metabolic acidosis. The study dosing (TRC101 or placebo) will continue for 12 weeks once daily. The maximum study duration is anticipated to be up to 16 weeks.

Official Title
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A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TRC101 in Subjects With Chronic Kidney Disease and Metabolic Acidosis

Conditions
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Metabolic Acidosis

Intervention / Treatment
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* Drug: TRC101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Blood bicarbonate level of 12 to 20 mEq/L. Estimated glomerular filtration rate (eGFR) of 20 to 40 mL/min/1.73m2. Stable kidney function defined as <=20% variability in eGFR during screening period. Key Exclusion Criteria: Any level of low blood bicarbonate during the screening period that in the opinion of the Investigator, requires emergency intervention or evaluation for an acute acidotic process. Anuria, dialysis, acute kidney injury, or history of acute kidney insufficiency within 3 months prior to screening. Heart failure with maximum New York Heart Association (NYHA) Class IV symptoms or that required hospitalization during the preceding 6 months. Heart or kidney transplant. Chronic obstructive pulmonary disease (COPD) that is treated with chronic oral steroids, that requires the subject to be on oxygen, or that required hospitalization within the previous 6 months. Change in doses to alkali therapy in the 4 weeks prior to screening. History or current diagnosis of diabetic gastroparesis, bowel obstruction, swallowing disorders, inflammatory bowel disease, major gastrointestinal surgery, frequent diarrhea or active gastric/duodenal ulcers. Serum calcium <= 8.0 mg/dL at screening. Planned initiation of renal replacement therapy within 12 weeks following randomization. Use of polymeric binder drugs within 14 days prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TRC101<br>Administered once daily (QD) for 12 weeks | Drug: TRC101<br>* Oral suspension<br>* Other names: Veverimer;|
| Placebo Comparator: Placebo<br>Administered once daily (QD) for 12 weeks | Drug: Placebo<br>* Oral suspension<br>|

What is the study measuring?
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Primary 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 | Composite endpoint of the percentage of subjects having a change from baseline in serum bicarbonate ≥ 4 mEq/L or having serum bicarbonate in the normal range (22 - 29 mEq/L) at the end of treatment (Week 12 Visit). | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Treatment in Serum Bicarbonate | Mean change from baseline to end of treatment (Week 12 Visit) in serum bicarbonate | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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blood bicarbonate, kidney disease