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CompletedNCT03390842Updated Oct 22, 2021Results posted

Long-term Safety Extension to Study TRCA-301

A Phase 3 interventional study of TRC101 and Placebo in Metabolic Acidosis, sponsored by Tricida, Inc.. Completed at 29 sites in 7 countries. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2021-10-22.

Sponsored by Tricida, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
196
Allocation
Randomized
Ages
18 Years to 85 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Metabolic Acidosis

Keywords

  • blood bicarbonate, kidney disease
03

In context

Acidosis

111 studies on the registry are indexed under Acidosis; 19 are open to participants now.

This study's enrollment of 196 is above the median of 52 across 79 interventional studies indexed under Acidosis.

Browse Acidosis studies →

Lead sponsor

Tricida, Inc. is the lead sponsor of 4 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  • Completed the 12-week treatment period and attended the Week 12 Visit in the parent study TRCA-301.
  • Blood bicarbonate level of >= 12 mEq/L at the Week 12 Visit in the parent study TRCA-301.

Key Exclusion Criteria:

  • Any level of low blood bicarbonate at the Week 12 Visit that, in the opinion of the Investigator, requires emergency intervention or evaluation for an acute acidotic process.
  • Required dialysis for acute kidney injury or worsening CKD during the parent study TRCA-301.
  • Planned initiation of renal replacement therapy within 6 months following study entry.
  • History or current diagnosis of diabetic gastroparesis, bowel obstruction, swallowing disorders, severe gastrointestinal disorders, inflammatory bowel disease, major gastrointestinal surgery, or active gastric/duodenal ulcers.
  • Serum calcium \<= 8.0 mg/dL at the Week 10 in the parent study TRCA-301.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
196 participants (actual)

Study arms

  • Experimental
    TRC101

    Administered once daily (QD) for 40 weeks

    Drug: TRC101

  • Placebo comparator
    Placebo

    Administered once daily (QD) for 40 weeks

    Drug: Placebo

Interventions

  • DrugTRC101

    Oral suspension

    Also known as: Veverimer

  • DrugPlacebo

    Oral suspension

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Week 12 Visit in the parent study, TRCA-301, to the Week 54 Visit in the extension study, TRCA-301E.

Secondary outcomes

  1. 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).

    Time frame: Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.

  2. Change From Baseline in Serum Bicarbonate at the End of Treatment

    Change from baseline in serum bicarbonate at the end of treatment (Week 52).

    Time frame: Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.

  3. 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.

    Time frame: Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.

  4. 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.

    Time frame: Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.

07

Results

Posted Oct 22, 2021

Participant flow

Participant flow — Overall Study
MilestoneTRC101 Treatment ArmPlacebo Treatment Arm
Started11482
Completed11174
Not completed38

Outcome measures

PrimaryIncidence 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.

Time frame:
Week 12 Visit in the parent study, TRCA-301, to the Week 54 Visit in the extension study, TRCA-301E.
Reported as:
Number · percentage of participants
Incidence of Adverse Events, Serious Adverse Events, and Adverse Events Leading to Withdrawal.
percentage of participantsTRC101 Treatment ArmPlacebo Treatment Arm
Incidence of Adverse Events, Serious Adverse Events, and Adverse Events Leading to Withdrawal.01.2
SecondarySubjects 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).

Time frame:
Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.
Reported as:
Number · percentage of participants
Subjects With Change From Baseline in Serum Bicarbonate of ≥ 4 mEq/L or Serum Bicarbonate Within the Normal Range
percentage of participantsTRC101 Treatment ArmPlacebo Treatment Arm
Subjects With Change From Baseline in Serum Bicarbonate of ≥ 4 mEq/L or Serum Bicarbonate Within the Normal Range62.7 (53.0 to 71.8)37.8 (26.8 to 49.9)
Statistical analysis
  • TRC101 Treatment Arm vs Placebo Treatment Arm · Fisher Exact · p = = 0.0015 · Difference in % of subjects: 24.9 · 95% CI 10.2 to 38.7
  • TRC101 Treatment Arm vs Placebo Treatment Arm · Fisher Exact · p = = 0.0015 · Treatment difference in % of subjects: 24.4 · 95% CI 9.7 to 38.2
  • TRC101 Treatment Arm vs Placebo Treatment Arm · Fisher Exact · p = < 0.0001 · Treatment difference in % of subjects: 30.2 · 95% CI 15.6 to 43.7
SecondaryChange From Baseline in Serum Bicarbonate at the End of Treatment

Change from baseline in serum bicarbonate at the end of treatment (Week 52).

Time frame:
Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.
Reported as:
Least squares mean · mEq/L
Change From Baseline in Serum Bicarbonate at the End of Treatment
mEq/LTRC101 Treatment ArmPlacebo Treatment Arm
Change From Baseline in Serum Bicarbonate at the End of Treatment4.70 ± 0.3352.71 ± 0.403
Statistical analysis
  • TRC101 Treatment Arm vs Placebo Treatment Arm · Mixed-effect repeated measures model · p = = 0.0002 · Treatment difference in ls means: 1.99 · 95% CI 0.96 to 3.03Standard error presented above is for the LS mean.
SecondaryChange 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.

Time frame:
Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.
Reported as:
Mean · KDQOL-PFD total score
Change From Baseline in the Total Score of the KDQOL-PFD at the End of Treatment
KDQOL-PFD total scoreTRC101 Treatment ArmPlacebo Treatment Arm
Change From Baseline in the Total Score of the KDQOL-PFD at the End of Treatment11.42 ± 2.201-0.71 ± 2.268
Statistical analysis
  • TRC101 Treatment Arm vs Placebo Treatment Arm · ANCOVA · p = < 0.0001 (p-value based on analysis of covariance model with rank of change from baseline in total score as dependent variable; treatment (PBO or TRC101) as a fixed effect; and baseline total score, Baseline eGFR, Baseline Bicarbonate as continuous covariates.)
SecondaryChange 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.

Time frame:
Baseline in the parent study, TRCA-301, to the Week 52 Visit in the extension study, TRCA-301E.
Reported as:
Mean · seconds
Change From Baseline in the Duration of Repeated Chair Stand Test at the End of Treatment
secondsTRC101 Treatment ArmPlacebo Treatment Arm
Change From Baseline in the Duration of Repeated Chair Stand Test at the End of Treatment-4.28 ± 1.240-1.42 ± 1.248
Statistical analysis
  • TRC101 Treatment Arm vs Placebo Treatment Arm · ANCOVA · p = < 0.0001

Adverse events

Collected over Week 12 visit in the parent study, TRCA-301, to the Week 54 follow-up visit in the extension study, TRCA-301E.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
TRC101 Treatment Arm0/112 (0%)2/112 (1.8%)78/112 (69.6%)
Placebo Treatment Arm2/81 (2.5%)4/81 (4.9%)39/81 (48.1%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
EventTRC101 Treatment ArmPlacebo Treatment Arm
Cardiac failure congestiveCardiac disorders0/1121/81
Cerebrovascular accidentNervous system disorders0/1121/81
Renal impairmentRenal and urinary disorders0/1121/81
AzotaemiaRenal and urinary disorders0/1121/81
HyponatraemiaMetabolism and nutrition disorders0/1121/81
HyperkalaemiaMetabolism and nutrition disorders0/1121/81
PneumoniaInfections and infestations0/1121/81
Angina unstableCardiac disorders1/1120/81
Cardiac failureCardiac disorders1/1120/81
Abdominal discomfortGastrointestinal disorders1/1120/81
Most frequent other events
Most frequent other events
EventTRC101 Treatment ArmPlacebo Treatment Arm
HeadacheNervous system disorders17/11220/81
HyperkalaemiaMetabolism and nutrition disorders16/1128/81
InfluenzaInfections and infestations12/1126/81
Renal impairmentRenal and urinary disorders5/1127/81
FlatulenceGastrointestinal disorders8/1125/81
CoughRespiratory, thoracic and mediastinal disorders7/1123/81
DiarrhoeaGastrointestinal disorders7/1125/81
AnaemiaBlood and lymphatic system disorders6/1121/81

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)TRC101 Treatment ArmPlacebo Treatment ArmTotal
<=18 years000
Between 18 and 65 years5644100
>=65 years583896
Age, Continuous
Age, Continuous(years)TRC101 Treatment ArmPlacebo Treatment ArmTotal
Mean62.9 ± 12.0761.7 ± 11.8862.4 ± 11.98
Sex: Female, Male
Sex: Female, Male(Participants)TRC101 Treatment ArmPlacebo Treatment ArmTotal
Female463177
Male6851119
Race (NIH/OMB)
Race (NIH/OMB)(Participants)TRC101 Treatment ArmPlacebo Treatment ArmTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American134
White11379192
More than one race000
Unknown or Not Reported000
History of Hypertension
History of Hypertension(Participants)TRC101 Treatment ArmPlacebo Treatment ArmTotal
Count of participants11079189
History of Diabetes Mellitus
History of Diabetes Mellitus(Participants)TRC101 Treatment ArmPlacebo Treatment ArmTotal
Count of participants7057127
History of Congestive Heart Failure
History of Congestive Heart Failure(Participants)TRC101 Treatment ArmPlacebo Treatment ArmTotal
Count of participants342862
Baseline eGFR
Baseline eGFR(mL/min/1.73m^2)TRC101 Treatment ArmPlacebo Treatment ArmTotal
Mean29.4 ± 6.4127.9 ± 5.4228.8 ± 6.05

1 further baseline measures are reported on the registry.

08

Study locations

29 sites
  • Investigative Site 55
    Phoenix, Arizona 85032, United States
  • Investigative Site 91
    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
09

References and documents

Publications

  • 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. PubMed 31248662 ↗
  • 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. PubMed 35216581 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 22, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03390842
Lead sponsor
Tricida, Inc.
Responsible party
Sponsor
First posted
Jan 4, 2018
Start date
Dec 20, 2017
Primary completion
Feb 22, 2019
Completion
Feb 22, 2019
Results posted
Oct 22, 2021
Last update
Oct 22, 2021

Study contacts

Clinical Operations
study director · Tricida, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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