Clinical trial NCT02809183: Evaluation of TRC101 in Subjects With Chronic Kidney Disease and Metabolic Acidosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acidosis
Keywords: metabolic acidosis
serum bicarbonate
kidney disease
Lead sponsor: Tricida, Inc.
Sponsor class: INDUSTRY
First posted: 2016-06-22
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Number of Subjects Who Discontinued Study Drug Due to a TEAE
timeFrame: Through treatment period completion (Day 15)
measure: Change From Baseline to the End of Treatment (Day 15) in Serum Bicarbonate Within Each Individual TRC101 Dose Group
timeFrame: Baseline and Day 15
Secondary outcomes:
measure: Comparison of Change From Baseline in Serum Bicarbonate at Day 15 Between Each TRC101 Dose Group Versus Placebo
timeFrame: Baseline and Day 15
measure: Change From Baseline in Serum Bicarbonate at Day 15 Within the Combined TRC101 Treatment Group
timeFrame: Baseline and Day 15
measure: Comparison of Change From Baseline in Serum Bicarbonate at Day 15 Between the Combined TRC101 Treatment Group Versus Placebo
timeFrame: Baseline and Day 15
measure: 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
timeFrame: Baseline and Day 15
measure: Change From Baseline in Serum Bicarbonate at Day 15 Within the TRC101 6g QD Dose Group
timeFrame: Baseline and Day 15
measure: Change From Baseline in Serum Bicarbonate at Day 15 Comparison Between the TRC101 6g QD Dose Group Versus Placebo
timeFrame: Baseline and Day 15
measure: Change From Baseline in Serum Bicarbonate at Day 15 Comparison Between the TRC101 6g QD Dose Group Versus the TRC101 3g BID Dose Group
timeFrame: Baseline and Day 15
measure: 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
timeFrame: Baseline and Day 15
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Investigative Site 1
city: Tbilisi
country: Georgia
facility: Investigative Site 3
city: Tbilisi
country: Georgia
facility: Investigative Site 4
city: Tbilisi
country: Georgia
facility: Investigative Site 5
city: Tbilisi
country: Georgia
facility: Investigative Site 6
Study officials:
affiliation: Tricida, Inc.
name: Yuri Stasiv, PhD
role: STUDY_DIRECTOR
References:
citation: 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.