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This study is a 40-week, blinded, placebo-controlled extension of Study TRCA-301 (NCT03317444). Eligible subjects who complete the 12-week treatment period in Study TRCA-301 have the option to participate in this extension study evaluating the long-term safety and durability of effect of TRC101 in subjects with non-dialysis dependent chronic kidney disease and metabolic acidosis. Eligible subjects will be treated with TRC101 or placebo once daily (QD) on an out-patient basis for the subsequent 40 weeks. Subjects will continue to receive the same blinded treatment (TRC101 or placebo) that they received in Study TRCA-301.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TRC101 | Experimental | Administered once daily (QD) for 40 weeks |
|
| Placebo | Placebo Comparator | Administered once daily (QD) for 40 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TRC101 | Drug | Oral suspension |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Adverse Events, Serious Adverse Events, and Adverse Events Leading to Withdrawal. | The incidence of adverse events (AEs), serious adverse events (SAEs) and AEs leading to withdrawal. For incidence of AEs and SAEs, see Adverse Events Section. For incidence of AEs leading to withdrawal, see endpoint values below. | Week 12 Visit in the parent study, TRCA-301, to the Week 54 Visit in the extension study, TRCA-301E. |
| Measure | Description | Time Frame |
|---|---|---|
| Subjects With Change From Baseline in Serum Bicarbonate of ≥ 4 mEq/L or Serum Bicarbonate Within the Normal Range | Percent of subjects having a change from baseline in serum bicarbonate of at least 4 mEq/L or bicarbonate in the normal range (22 - 29 mEq/L) at the end of treatment (Week 52). | Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Operations | Tricida, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigative Site 55 | Phoenix | Arizona | 85032 | United States | ||
| Investigative Site 91 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31248662 | Result | Wesson DE, Mathur V, Tangri N, Stasiv Y, Parsell D, Li E, Klaerner G, Bushinsky DA. Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension. Lancet. 2019 Aug 3;394(10196):396-406. doi: 10.1016/S0140-6736(19)31388-1. Epub 2019 Jun 24. | |
| 35216581 |
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| ID | Title | Description |
|---|---|---|
| FG000 | TRC101 Treatment Arm | TRC101 was self-administered orally as an aqueous suspension, QD with food, at approximately the same time each day for 40 weeks. Subjects entered the study on the same blinded TRC101 dose they were receiving in the parent study, TRCA-301, as follows: 0, 3, 6 or 9 g TRC101 QD (0, 1, 2 or 3 packets, respectively). Subjects could have had a blinded dose adjustment using these same doses in accordance with a protocol-specified titration algorithm at each study visit. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 17, 2018 | Sep 24, 2021 |
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| Placebo |
| Drug |
Oral suspension |
|
| Change From Baseline in Serum Bicarbonate at the End of Treatment | Change from baseline in serum bicarbonate at the end of treatment (Week 52). | Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E. |
| Change From Baseline in the Total Score of the KDQOL-PFD at the End of Treatment | Change from baseline in the total score of the Kidney Disease Quality of Life Physical Function Domain (KDQOL-PFD) at the end of treatment. The KDQOL is a validated, kidney disease-specific measure of health-related quality of life. For study TRCA-301E, and the parent study TRCA-301, the 10-question Item 3 of the KDQOL, also known as the SF-36 Physical Function subscale, was selected to measure physical functioning and is referenced herein as the KDQOL-PFD. The KDQOL-PFD was chosen as a patient-reported outcome measurement to evaluate the effects of TRC101 on daily activities that may be adversely affected by loss of muscle caused by metabolic acidosis. The minimum score for each of the 10 questions is 0 (physical activity highly limited) and the maximum is 100 (physical activity not limited). The total KDQOL-PFD score is calculated by adding the scores for all 10 questions, for a minimum and maximum possible total KDQOL-PFD score of 0 or 100, respectively. | Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E. |
| Change From Baseline in the Duration of Repeated Chair Stand Test at the End of Treatment | Change from baseline in the duration of repeated chair stand test at the end of treatment (Week 52). The five-times repeated chair stand test was used as a measure of lower extremity muscle strength. In this test, the time it took for a subject to repeatedly stand from a chair five times was recorded. This test is among the group of measures (gait speed, chair stand, and balance tests) comprising the Short Physical Performance Battery (SPPB), which has been used as a predictive tool for possible disability and for monitoring physical functioning in older people. | Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E. |
| Los Angeles |
| California |
| 90022 |
| United States |
| Investigative Site 59 | Hialeah | Florida | 33015 | United States |
| Investigative Site 93 | Hollywood | Florida | 33024 | United States |
| Investigative Site 92 | Lauderdale Lakes | Florida | 33313 | United States |
| Investigative Site 95 | Atlanta | Georgia | 30342 | United States |
| Investigative Site 52 | San Antonio | Texas | 78215 | United States |
| Investigative Site 11 | Sofia | Bulgaria |
| Investigative Site 31 | Tbilisi | Georgia |
| Investigative Site 32 | Tbilisi | Georgia |
| Investigative Site 33 | Tbilisi | Georgia |
| Investigative Site 34 | Tbilisi | Georgia |
| Investigative Site 35 | Tbilisi | Georgia |
| Investigative Site 36 | Tbilisi | Georgia |
| Investigative Site 37 | Tbilisi | Georgia |
| Investigative Site 41 | Budapest | Hungary |
| Investigative Site 46 | Budapest | Hungary |
| Investigative Site 49 | Hódmezővásárhely | Hungary |
| Investigative Site 44 | Kistarcsa | Hungary |
| Investigative Site 61 | Vršac | Serbia |
| Investigative Site 72 | Jesenice | Slovenia |
| Investigative Site 71 | Maribor | Slovenia |
| Investigative Site 81 | Kharkiv | Ukraine |
| Investigative Site 83 | Kharkiv | Ukraine |
| Investigative Site 87 | Kharkiv | Ukraine |
| Investigative Site 88 | Kharkiv | Ukraine |
| Investigative Site 84 | Kyiv | Ukraine |
| Investigative Site 85 | Kyiv | Ukraine |
| Investigative Site 86 | Kyiv | Ukraine |
| Mathur VS, Wesson DE, Tangri N, Li E, Bushinsky DA. Effects of veverimer on serum bicarbonate and physical function in women with chronic kidney disease and metabolic acidosis: a subgroup analysis from a randomised, controlled trial. BMC Nephrol. 2022 Feb 25;23(1):82. doi: 10.1186/s12882-022-02690-1. |
| FG001 | Placebo Treatment Arm | Placebo was self-administered orally as an aqueous suspension, QD with food, at approximately the same time each day for 40 weeks. Subjects entered the study on the same blinded placebo dose they were receiving in the parent study, TRCA-301, as follows: 0, 1, 2 or 3 placebo packets QD. Subjects could have had a blinded dose adjustment using these same doses in accordance with a protocol-specified titration algorithm at each study visit. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | TRC101 Treatment Arm | TRC101 was self-administered orally as an aqueous suspension, QD with food, at approximately the same time each day for 40 weeks. Subjects entered the study on the same blinded TRC101 dose they were receiving in the parent study, TRCA-301, as follows: 0, 3, 6 or 9 g TRC101 QD (0, 1, 2 or 3 packets, respectively). Subjects could have had a blinded dose adjustment using these same doses in accordance with a protocol-specified titration algorithm at each study visit. |
| BG001 | Placebo Treatment Arm | Placebo was self-administered orally as an aqueous suspension, QD with food, at approximately the same time each day for 40 weeks. Subjects entered the study on the same blinded placebo dose they were receiving in the parent study, TRCA-301, as follows: 0, 1, 2 or 3 placebo packets QD. Subjects could have had a blinded dose adjustment using these same doses in accordance with a protocol-specified titration algorithm at each study visit. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Age (years) was calculated as the number of years between date of birth and date of informed consent in the parent study TRCA-301, expressed as an integer. | Count of Participants | Participants |
| |||||||||||||||||
| Age, Continuous | Age (years) was calculated as the number of years between date of birth and date of informed consent in the parent study TRCA-301, expressed as an integer. | Mean | Standard Deviation | years |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| History of Hypertension | Count of Participants | Participants |
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| History of Diabetes Mellitus | Count of Participants | Participants |
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| History of Congestive Heart Failure | Count of Participants | Participants |
| ||||||||||||||||||
| Baseline eGFR | Baseline eGFR is defined as the average of values of eGFR collected at the Screening 1 Visit, Screening 2 Visit, and Baseline Visit (i.e., Day 1 pre-dose) in the parent study TRCA-301, as measured by the central laboratory, based on serum creatinine values using the CKD-EPI formula. | Mean | Standard Deviation | mL/min/1.73m^2 |
| ||||||||||||||||
| Baseline Bicarbonate | Baseline Bicarbonate is defined as the average of the values of serum bicarbonate collected at the Screening 1 Visit, Screening 2 Visit, and Baseline Visit (i.e., Day 1 pre-dose) in the parent study TRCA-301, measured onsite using an i-STAT point-of-care device. | Mean | Standard Deviation | mEq/L |
|
| 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 | Incidence of Adverse Events, Serious Adverse Events, and Adverse Events Leading to Withdrawal. | The incidence of adverse events (AEs), serious adverse events (SAEs) and AEs leading to withdrawal. For incidence of AEs and SAEs, see Adverse Events Section. For incidence of AEs leading to withdrawal, see endpoint values below. | The TRCA-301E Safety Analysis Set included all subjects who received any amount of study drug (TRC101 or placebo) in Study TRCA-301E. | Posted | Number | percentage of participants | Week 12 Visit in the parent study, TRCA-301, to the Week 54 Visit in the extension study, TRCA-301E. |
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| Secondary | Subjects With Change From Baseline in Serum Bicarbonate of ≥ 4 mEq/L or Serum Bicarbonate Within the Normal Range | Percent of subjects having a change from baseline in serum bicarbonate of at least 4 mEq/L or bicarbonate in the normal range (22 - 29 mEq/L) at the end of treatment (Week 52). | The TRCA-301E Modified Intent-to-Treat (MITT) Analysis Set included all randomized subjects who had both baseline and at least one postbaseline serum bicarbonate value measured using the i-STAT device in the parent study, TRCA-301, and at least one serum bicarbonate value after the Week 12 Visit in Study TRCA-301E. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E. |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Serum Bicarbonate at the End of Treatment | Change from baseline in serum bicarbonate at the end of treatment (Week 52). | The TRCA-301E Modified Intent-to-Treat (MITT) Analysis Set included all randomized subjects who had both baseline and at least one postbaseline serum bicarbonate value measured using the i-STAT device in the parent study, TRCA-301, and at least one serum bicarbonate value after the Week 12 Visit in Study TRCA-301E. | Posted | Least Squares Mean | Standard Error | mEq/L | Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E. |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in the Total Score of the KDQOL-PFD at the End of Treatment | Change from baseline in the total score of the Kidney Disease Quality of Life Physical Function Domain (KDQOL-PFD) at the end of treatment. The KDQOL is a validated, kidney disease-specific measure of health-related quality of life. For study TRCA-301E, and the parent study TRCA-301, the 10-question Item 3 of the KDQOL, also known as the SF-36 Physical Function subscale, was selected to measure physical functioning and is referenced herein as the KDQOL-PFD. The KDQOL-PFD was chosen as a patient-reported outcome measurement to evaluate the effects of TRC101 on daily activities that may be adversely affected by loss of muscle caused by metabolic acidosis. The minimum score for each of the 10 questions is 0 (physical activity highly limited) and the maximum is 100 (physical activity not limited). The total KDQOL-PFD score is calculated by adding the scores for all 10 questions, for a minimum and maximum possible total KDQOL-PFD score of 0 or 100, respectively. | The TRCA-301E Modified Intent-to-Treat (MITT) Analysis Set included all randomized subjects who had both baseline and at least one postbaseline serum bicarbonate value measured using the i-STAT device in the parent study, TRCA-301, and at least one serum bicarbonate value after the Week 12 Visit in Study TRCA-301E. | Posted | Mean | Standard Error | KDQOL-PFD total score | Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E. |
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| Secondary | Change From Baseline in the Duration of Repeated Chair Stand Test at the End of Treatment | Change from baseline in the duration of repeated chair stand test at the end of treatment (Week 52). The five-times repeated chair stand test was used as a measure of lower extremity muscle strength. In this test, the time it took for a subject to repeatedly stand from a chair five times was recorded. This test is among the group of measures (gait speed, chair stand, and balance tests) comprising the Short Physical Performance Battery (SPPB), which has been used as a predictive tool for possible disability and for monitoring physical functioning in older people. | The TRCA-301E Modified Intent-to-Treat (MITT) Analysis Set included all randomized subjects who had both baseline and at least one postbaseline serum bicarbonate value measured using the i-STAT device in the parent study, TRCA-301, and at least one serum bicarbonate value after the Week 12 Visit in Study TRCA-301E. | Posted | Mean | Standard Error | seconds | Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E. |
|
Week 12 visit in the parent study, TRCA-301, to the Week 54 follow-up visit in the extension study, TRCA-301E.
The TRCA-301E Safety Analysis Set included all subjects who received any amount of study drug (TRC101 or placebo) in TRCA-301E. Three subjects were excluded (2 TRC101, 1 placebo) because they entered TRCA-301E on a dose hold and remained on the dose hold for the duration of the study because their bicarbonate levels remained within the normal range.
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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 | TRC101 Treatment Arm | TRC101 was self-administered orally as an aqueous suspension, QD with food, at approximately the same time each day for 40 weeks. Subjects entered the study on the same blinded TRC101 dose they were receiving in the parent study, TRCA-301, as follows: 0, 3, 6 or 9 g TRC101 QD (0, 1, 2 or 3 packets, respectively). Subjects could have had a blinded dose adjustment using these same doses in accordance with a protocol-specified titration algorithm at each study visit. | 0 | 112 | 2 | 112 | 78 | 112 |
| EG001 | Placebo Treatment Arm | Placebo was self-administered orally as an aqueous suspension, QD with food, at approximately the same time each day for 40 weeks. Subjects entered the study on the same blinded placebo dose they were receiving in the parent study, TRCA-301, as follows: 0, 1, 2 or 3 placebo packets QD. Subjects could have had a blinded dose adjustment using these same doses in accordance with a protocol-specified titration algorithm at each study visit. | 2 | 81 | 4 | 81 | 39 | 81 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure congestive | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
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| Angina unstable | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Renal impairment | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
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| Azotaemia | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
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| Chronic kidney disease | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Renal impairment | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Information | Tricida, Inc. | 415-429-7800 | medinfo@tricida.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 12, 2019 | Sep 24, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000138 | Acidosis |
| D007674 | Kidney Diseases |
| ID | Term |
|---|---|
| D000137 | Acid-Base Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C000630913 | veverimer |
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| >=65 years |
|
| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| OG001 | Placebo Treatment Arm | Placebo was self-administered orally as an aqueous suspension, QD with food, at approximately the same time each day for 40 weeks. Subjects entered the study on the same blinded placebo dose they were receiving in the parent study, TRCA-301, as follows: 0, 1, 2 or 3 placebo packets QD. Subjects could have had a blinded dose adjustment using these same doses in accordance with a protocol-specified titration algorithm at each study visit. |
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| OG001 |
| Placebo Treatment Arm |
Placebo was self-administered orally as an aqueous suspension, QD with food, at approximately the same time each day for 40 weeks. Subjects entered the study on the same blinded placebo dose they were receiving in the parent study, TRCA-301, as follows: 0, 1, 2 or 3 placebo packets QD. Subjects could have had a blinded dose adjustment using these same doses in accordance with a protocol-specified titration algorithm at each study visit. |
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