Trial | NCT02809183  Report issue

Title

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

  • Phase

    Phase 1/Phase 2

  • Study Type

    Interventional

  • Intervention/Treatment

    Veverimer ...

  • Study Participants

    135
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 Started
Mar 31
2016
Primary Completion
Nov 30
2016
Study Completion
Nov 30
2016
Results Posted
Jan 14
2020
Last Update
Jan 14
2020

Drug Placebo

oral suspension

Drug TRC101

oral suspension

  • Other names: Veverimer

Placebo-BID Placebo Comparator

Administered twice daily (BID) for 14 days

TRC101 (1.5g BID) Experimental

Administered twice daily (BID) for 14 days

TRC101 (3g BID) Experimental

Administered twice daily (BID) for 14 days

TRC101 (4.5g BID) Experimental

Administered twice daily (BID) for 14 days

TRC101 (6g QD) Experimental

Administered once daily (QD) for 14 days

Placebo-QD Placebo Comparator

Administered once daily (QD) for 14 days

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.

Summary

Pooled Placebo

1.5g TRC101 BID

3g TRC101 BID

4.5g TRC101 BID

6g TRC101 QD

All Events

Event Type Organ System Event Term Pooled Placebo 1.5g TRC101 BID 3g TRC101 BID 4.5g TRC101 BID 6g TRC101 QD

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

Pooled Placebo

-0.2
mEq/L (Least Squares Mean)
Standard Error: 0.4

1.5g TRC101 BID

3.2
mEq/L (Least Squares Mean)
Standard Error: 0.4

3g TRC101 BID

3.0
mEq/L (Least Squares Mean)
Standard Error: 0.4

4.5g TRC101 BID

3.7
mEq/L (Least Squares Mean)
Standard Error: 0.4

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.

Pooled Placebo

≥ 1 Mild TEAE

≥ 1 Moderate TEAE

≥ 1 Serious TEAE

≥ 1 Severe TEAE

Study Drug Discontinuation Due to TEAE

Subjects Reporting any TEAE

1.5g TRC101 BID

≥ 1 Mild TEAE

≥ 1 Moderate TEAE

≥ 1 Serious TEAE

≥ 1 Severe TEAE

Study Drug Discontinuation Due to TEAE

Subjects Reporting any TEAE

3g TRC101 BID

≥ 1 Mild TEAE

≥ 1 Moderate TEAE

≥ 1 Serious TEAE

≥ 1 Severe TEAE

Study Drug Discontinuation Due to TEAE

Subjects Reporting any TEAE

4.5g TRC101 BID

≥ 1 Mild TEAE

≥ 1 Moderate TEAE

≥ 1 Serious TEAE

≥ 1 Severe TEAE

Study Drug Discontinuation Due to TEAE

Subjects Reporting any TEAE

6g TRC101 QD

≥ 1 Mild TEAE

≥ 1 Moderate TEAE

≥ 1 Serious TEAE

≥ 1 Severe TEAE

Study Drug Discontinuation Due to TEAE

Subjects Reporting any TEAE

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

Combined TRC101

3.3
mEq/L (Least Squares Mean)
Standard Error: 0.2

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

Pooled Placebo

-0.2
mEq/L (Least Squares Mean)
Standard Error: 0.4

Combined TRC101

3.3
mEq/L (Least Squares Mean)
Standard Error: 0.2

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

Pooled Placebo

=> 2 mEq/L Baseline Serum Bicarbonate

=> 3 mEq/L Baseline Serum Bicarbonate

=> 4 mEq/L Baseline Serum Bicarbonate

1.5g TRC101 BID

=> 2 mEq/L Baseline Serum Bicarbonate

=> 3 mEq/L Baseline Serum Bicarbonate

=> 4 mEq/L Baseline Serum Bicarbonate

3g TRC101 BID

=> 2 mEq/L Baseline Serum Bicarbonate

=> 3 mEq/L Baseline Serum Bicarbonate

=> 4 mEq/L Baseline Serum Bicarbonate

4.5g TRC101 BID

=> 2 mEq/L Baseline Serum Bicarbonate

=> 3 mEq/L Baseline Serum Bicarbonate

=> 4 mEq/L Baseline Serum Bicarbonate

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

6g TRC101 QD

3.5
mEq/L (Least Squares Mean)
Standard Error: 0.4

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

Pooled Placebo

-0.2
mEq/L (Least Squares Mean)
Standard Error: 0.4

6g TRC101 QD

3.5
mEq/L (Least Squares Mean)
Standard Error: 0.4

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

3g TRC101 BID

3.0
mEq/L (Least Squares Mean)
Standard Error: 0.4

6g TRC101 QD

3.5
mEq/L (Least Squares Mean)
Standard Error: 0.4

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

Pooled Placebo

=> 2 mEq/L Baseline Serum Bicarbonate

=> 3 mEq/L Baseline Serum Bicarbonate

=> 4 mEq/L Baseline Serum Bicarbonate

6g TRC101 QD

=> 2 mEq/L Baseline Serum Bicarbonate

=> 3 mEq/L Baseline Serum Bicarbonate

=> 4 mEq/L Baseline Serum Bicarbonate

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

Pooled Placebo

-0.2
mEq/L (Least Squares Mean)
Standard Error: 0.4

1.5g TRC101 BID

3.2
mEq/L (Least Squares Mean)
Standard Error: 0.4

3g TRC101 BID

3.0
mEq/L (Least Squares Mean)
Standard Error: 0.4

4.5g TRC101 BID

3.7
mEq/L (Least Squares Mean)
Standard Error: 0.4

Total

135
Participants

Age, Continuous

60.3
years (Mean)
Standard Deviation: 12.44

Diabetes

94
Participants

eGFR

35.70
mL/min/1.73m^2 (Mean)
Standard Deviation: 12.419

Heart Failure

29
Participants

Hypertension

126
Participants

Serum Bicarbonate

17.72
mEq/L (Mean)
Standard Deviation: 1.197

Sex: Female, Male

Overall Study

Placebo BID

1.5g TRC101 BID

3g TRC101 BID

4.5g TRC101 BID

Placebo QD

6g TRC101 QD