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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-004327-31 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | oral suspension |
| |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yuri Stasiv, PhD | Tricida, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigative Site 1 | Sofia | Bulgaria | ||||
| Investigative Site 3 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29102959 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo BID | Placebo administered twice daily (BID) for 14 days |
| FG001 | 1.5g TRC101 BID | 1.5g TRC101 administered twice daily (BID) for 14 days |
| FG002 | 3g TRC101 BID | 3g TRC101 administered twice daily (BID) for 14 days |
| FG003 | 4.5g TRC101 BID | 4.5g TRC101 administered twice daily (BID) for 14 days |
| FG004 | Placebo QD | Placebo administered once daily (QD) for 14 days |
| FG005 | 6g TRC101 QD | 6g TRC101 administered once daily (QD) for 14 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Intent-to-treat (ITT) population
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| ID | Title | Description |
|---|---|---|
| BG000 | Pooled Placebo | Pooled placebo treatment groups (Placebo administered twice daily [BID] for 14 days + Placebo administered once daily [QD] for 14 days) |
| BG001 | 1.5g TRC101 BID |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Safety Analysis Set | Posted | Count of Participants | Participants | Through treatment period completion (Day 15) |
|
Through treatment period completion (Day 15)
All subjects completed dosing per protocol and are included in the safety results.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pooled Placebo | Pooled Placebo treatment group (Placebo administered twice daily [BID] for 14 days + Placebo administered once daily [QD] for 14 days) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (19.0) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Information | Tricida, Inc. | 415-429-7800 | medinfo@tricida.com |
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| ID | Term |
|---|---|
| D000138 | Acidosis |
| D007674 | Kidney Diseases |
| ID | Term |
|---|---|
| D000137 | Acid-Base Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| C000630913 | veverimer |
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| TRC101 |
| Drug |
oral suspension |
|
|
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 |
| Tbilisi |
| Georgia |
| Investigative Site 4 | Tbilisi | Georgia |
| Investigative Site 5 | Tbilisi | Georgia |
| Investigative Site 6 | Tbilisi | Georgia |
1.5g TRC101 administered twice daily (BID) for 14 days
| BG002 | 3g TRC101 BID | 3g TRC101 administered twice daily (BID) for 14 days |
| BG003 | 4.5g TRC101 BID | 4.5g TRC101 administered twice daily (BID) for 14 days |
| BG004 | 6g TRC101 QD | 6g TRC101 administered once daily (QD) for 14 days |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Diabetes | Count of Participants | Participants |
|
| Hypertension | Count of Participants | Participants |
|
| Heart Failure | Count of Participants | Participants |
|
| Serum Bicarbonate | Mean | Standard Deviation | mEq/L |
|
| eGFR | Mean | Standard Deviation | mL/min/1.73m^2 |
|
1.5g TRC101 administered twice daily (BID) for 14 days |
| OG002 | 3g TRC101 BID | 3g TRC101 administered twice daily (BID) for 14 days |
| OG003 | 4.5g TRC101 BID | 4.5g TRC101 administered twice daily (BID) for 14 days |
| OG004 | 6g TRC101 QD | 6g TRC101 administered once daily (QD) for 14 days |
|
|
| 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 | Full Analysis Set | Posted | Least Squares Mean | Standard Error | mEq/L | 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 | Full Analysis Set | Posted | Least Squares Mean | Standard Error | mEq/L | 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 | Full Analysis Set | Posted | Least Squares Mean | Standard Error | mEq/L | 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 | Full Analysis Set | Posted | Least Squares Mean | Standard Error | mEq/L | 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 | Full Analysis Set | Posted | Count of Participants | Participants | 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 | Full Analysis Set | Posted | Least Squares Mean | Standard Error | mEq/L | 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 | Full Analysis Set | Posted | Least Squares Mean | Standard Error | mEq/L | 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 | Full Analysis Set | Posted | Least Squares Mean | Standard Error | mEq/L | 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 | Full Analysis Set | Posted | Count of Participants | Participants | Baseline and Day 15 |
|
|
|
|
| 0 |
| 31 |
| 0 |
| 31 |
| 12 |
| 31 |
| EG001 | 1.5g TRC101 BID | 1.5g TRC101 administered twice daily (BID) for 14 days | 0 | 25 | 0 | 25 | 13 | 25 |
| EG002 | 3g TRC101 BID | 3g TRC101 administered twice daily (BID) for 14 days | 0 | 25 | 0 | 25 | 9 | 25 |
| EG003 | 4.5g TRC101 BID | 4.5g TRC101 administered twice daily (BID) for 14 days | 0 | 26 | 0 | 26 | 17 | 26 |
| EG004 | 6g TRC101 QD | 6g TRC101 administered once daily (QD) for 14 days | 0 | 28 | 0 | 28 | 13 | 28 |
| Constipation | Gastrointestinal disorders | MedDRA (19.0) |
|
| Glomerular filtration rate decreased | Investigations | MedDRA (19.0) |
|
| Blood glucose increased | Investigations | MedDRA (19.0) |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (19.0) |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (19.0) |
|
| Headache | Nervous system disorders | MedDRA (19.0) |
|
| Hypertension | Vascular disorders | MedDRA (19.0) |
|
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| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
The null hypothesis is that the mean change from baseline within the 1.5g TRC101 BID treatment group = 0 mEq/L.
| Mixed Models Analysis |
| < 0.0001 |
The null hypothesis is that the mean change from baseline within the 1.5g TRC101 BID group = 0 mEq/L |
| Group LS mean |
| 3.2 |
| Standard Error of the Mean |
| 0.4 |
| 2-Sided |
| 95 |
| 2.4 |
| 4.0 |
| Other |
Single-group test |
| Mixed Models Analysis | < 0.0001 | The null hypothesis is the 3g TRC101 BID treatment group mean change from baseline = 0 mEq/L. | Group LS mean | 3.0 | Standard Error of the Mean | 0.4 | 2-Sided | 95 | 2.2 | 3.8 | Other | Single-group test |
| Mixed Models Analysis | < 0.0001 | The null hypothesis is the 4.5g TRC101 BID treatment group mean change from baseline = 0 mEq/L | Group LS mean | 3.7 | Standard Error of the Mean | 0.4 | 2-Sided | 95 | 2.9 | 4.5 | Other | Single-group test |
| Mixed Models Analysis |
| < 0.0001 |
The null hypothesis is the difference between treatment groups (3g TRC101 BID - Pooled Placebo) in the mean change from baseline = 0 mEq/L. |
| Difference between group LS means |
| 3.2 |
| Standard Error of the Mean |
| 0.5 |
| 2-Sided |
| 95 |
| 2.2 |
| 4.3 |
| Other |
Two-group test |
| Mixed Models Analysis | < 0.0001 | The null hypothesis is the difference between the treatment groups (4.5g TRC101 BID - Pooled Placebo) in the mean change from baseline = 0 mEq/L. | Difference between group LS means | 3.9 | Standard Error of the Mean | 0.5 | 2-Sided | 95 | 2.9 | 5.0 | Other | Two-group test |
| => 3 mEq/L Baseline Serum Bicarbonate |
|
| => 4 mEq/L Baseline Serum Bicarbonate |
|
| Fisher Exact |
| < 0.0001 |
The null hypothesis is that the difference between treatment groups (1.5g TRC101 BID - Pooled Placebo) in proportion of subjects whose serum bicarbonate increased from baseline to Day 15 by => 3 mEq/L = 0. |
| Other |
Two-group test |
| Fisher Exact | 0.0074 | The null hypothesis is that the difference between treatment groups (1.5g TRC101 BID - Pooled Placebo) in proportion of subjects whose serum bicarbonate increased from baseline to Day 15 by => 4 mEq/L = 0. | Other | Two-group test |
| Fisher Exact | 0.0012 | The null hypothesis is that the difference between treatment groups (3g TRC101 BID - Pooled Placebo) in proportion of subjects whose serum bicarbonate increased from baseline to Day 15 by => 2 mEq/L = 0. | Other | Two-group test |
| Fisher Exact | 0.0032 | The null hypothesis is that the difference between treatment groups (3g TRC101 BID - Pooled Placebo) in proportion of subjects whose serum bicarbonate increased from baseline to Day 15 by => 3 mEq/L = 0. | Other | Two-group test |
| Fisher Exact | 0.0013 | The null hypothesis is that the difference between treatment groups (3g TRC101 BID - Pooled Placebo) in proportion of subjects whose serum bicarbonate increased from baseline to Day 15 by => 4 mEq/L = 0. | Other | Two-group test |
| Fisher Exact | < 0.0001 | The null hypothesis is that the difference between treatment groups (4.5g TRC101 BID - Pooled Placebo) in proportion of subjects whose serum bicarbonate increased from baseline to Day 15 by => 2 mEq/L = 0. | Other | Two-group test |
| Fisher Exact | < 0.0001 | The null hypothesis is that the difference between treatment groups (4.5g TRC101 BID - Pooled Placebo) in proportion of subjects whose serum bicarbonate increased from baseline to Day 15 by => 3 mEq/L = 0. | Other | Two-group test |
| Fisher Exact | < 0.0006 | The null hypothesis is that the difference between treatment groups (4.5g TRC101 BID - Pooled Placebo) in proportion of subjects whose serum bicarbonate increased from baseline to Day 15 by => 4 mEq/L = 0. | Other | Two-group test |
| => 4 mEq/L Baseline Serum Bicarbonate |
|
| Fisher Exact |
| 0.0003 |
The null hypothesis is that the difference between treatment groups (6g TRC101 QD - Pooled Placebo) in the proportion of subjects whose serum bicarbonate increased from baseline to Day 15 by => 3 mEq/L = 0. |
| Other |
Two-group test |
| Fisher Exact | 0.0003 | The null hypothesis is that the difference between treatment groups (6g TRC101 QD - Pooled Placebo) in the proportion of subjects whose serum bicarbonate increased from baseline to Day 15 by => 4 mEq/L = 0. | Other | Two-group test |