AcidosisPhase 1/2NCT02809183

Evaluation of TRC101 in Subjects With Chronic Kidney Disease and Metabolic Acidosis

A Phase 1/2 study testing TRC101 in people with Acidosis, run by Tricida, Inc. at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Acidosis
What is being tested?: TRC101
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 135 participants
Where: 5 sitesin 2 countries
Study dates: Mar 2016to Nov 2016
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Estimated glomerular filtration rate (eGFR) of 20 to <60 mL/min/1.73m2
Serum bicarbonate level of 12 to 20 mEq/L

Who cannot join

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.

Trial locations and contacts

5 sites in 2 countries.

Country

City, postcode or hospital

5 sites in 2 countries

Georgia4 sites

Investigative Site 3
Tbilisi
Investigative Site 4
Tbilisi
Investigative Site 5
Tbilisi
Investigative Site 6
Tbilisi

Other trials in Georgia

Bulgaria1 site

Investigative Site 1
Sofia

Other trials in Bulgaria

About this study

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

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.

Conditions: Acidosis
Being tested: Placebo, TRC101
Keywords: metabolic acidosis, serum bicarbonate, kidney disease
Medical subject headings: Acidosis, Kidney Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
oral suspension
TRC101Drug
Also called Veverimer
oral suspension

Study groups in NCT02809183
Study group	Role	What they receive
Placebo-BID	Placebo comparator	Administered twice daily (BID) for 14 days Receives: Drug: Placebo
TRC101 (1.5g BID)	Experimental	Administered twice daily (BID) for 14 days Receives: Drug: TRC101
TRC101 (3g BID)	Experimental	Administered twice daily (BID) for 14 days Receives: Drug: TRC101
TRC101 (4.5g BID)	Experimental	Administered twice daily (BID) for 14 days Receives: Drug: TRC101
TRC101 (6g QD)	Experimental	Administered once daily (QD) for 14 days Receives: Drug: TRC101
Placebo-QD	Placebo comparator	Administered once daily (QD) for 14 days Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
Measured: Baseline and Day 15

Secondary outcomes (8)

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
Measured: Baseline and Day 15
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline and Day 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2016Nov 2016

First posted22 Jun 2016 (estimated)
Study startMar 2016
Primary completionNov 2016
Study completionNov 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for AcidosisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 135 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02809183
Sponsor's protocol ID: TRCA-101
Other IDs: 2015-004327-31, 2015
Status last verified: Jan 2020
First submitted: 14 Jun 2016
Last updated: 14 Jan 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 29102959

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Acidosis trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02809183
Acronym / sponsor ID: TRCA-101
Conditions: Acidosis
Keywords: metabolic acidosis, serum bicarbonate, kidney disease
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 135 participants (actual)
Lead sponsor: Tricida, Inc.Industry (pharma, biotech, devices)
Study start: Mar 2016 (actual)
Primary completion: Nov 2016 (actual)
Study completion: Nov 2016 (actual)
First posted: 22 Jun 2016 (estimated)
Results: Posted 14 Jan 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The maximum study duration per subject was anticipated to be up to 42 days.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 6

Arm	Type	Receives
Placebo-BID	Placebo comparator	Drug: PlaceboAdministered twice daily (BID) for 14 days
TRC101 (1.5g BID)	Experimental	Drug: TRC101Administered twice daily (BID) for 14 days
TRC101 (3g BID)	Experimental	Drug: TRC101Administered twice daily (BID) for 14 days
TRC101 (4.5g BID)	Experimental	Drug: TRC101Administered twice daily (BID) for 14 days
TRC101 (6g QD)	Experimental	Drug: TRC101Administered once daily (QD) for 14 days
Placebo-QD	Placebo comparator	Drug: PlaceboAdministered once daily (QD) for 14 days

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Estimated glomerular filtration rate (eGFR) of 20 to <60 mL/min/1.73m2
Serum bicarbonate level of 12 to 20 mEq/L

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Placebooral suspension	Drug	Placebo-BID, Placebo-QD
TRC101Also: Veverimeroral suspension	Drug	TRC101 (1.5g BID), TRC101 (3g BID), TRC101 (4.5g BID), TRC101 (6g QD)

Primary outcome

Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Number of Subjects Who Discontinued Study Drug Due to a TEAE
Time frame: Through treatment period completion (Day 15)
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.
Change From Baseline to the End of Treatment (Day 15) in Serum Bicarbonate Within Each Individual TRC101 Dose Group
Time frame: Baseline and Day 15
Serum bicarbonate at Day 15 minus serum bicarbonate at Baseline

8 secondary outcomes

Comparison of Change From Baseline in Serum Bicarbonate at Day 15 Between Each TRC101 Dose Group Versus Placebo
Time frame: Baseline and Day 15
Change From Baseline in Serum Bicarbonate at Day 15 Within the Combined TRC101 Treatment Group
Time frame: Baseline and Day 15
Comparison of Change From Baseline in Serum Bicarbonate at Day 15 Between the Combined TRC101 Treatment Group Versus Placebo
Time frame: 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
Time frame: Baseline and Day 15
Change From Baseline in Serum Bicarbonate at Day 15 Within the TRC101 6g QD Dose Group
Time frame: Baseline and Day 15
Change From Baseline in Serum Bicarbonate at Day 15 Comparison Between the TRC101 6g QD Dose Group Versus Placebo
Time frame: 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
Time frame: 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
Time frame: Baseline and Day 15

Results and safety

Results posted to the registry on 14 Jan 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo BID	25	25
1.5g TRC101 BID	25	25
3g TRC101 BID	25	25
4.5g TRC101 BID	26	26
Placebo QD	6	6
6g TRC101 QD	28	28

Primary outcome: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Number of Subjects Who Discontinued Study Drug Due to a TEAE

Time frame: Through treatment period completion (Day 15). Count of participants. Unit: Participants

Measure	Pooled Placebo n = 31	1.5g TRC101 BID n = 25	3g TRC101 BID n = 25	4.5g TRC101 BID n = 26	6g TRC101 QD n = 28
Subjects Reporting any TEAE	14	13	9	17	17
≥ 1 Mild TEAE	11	9	8	14	15
≥ 1 Moderate TEAE	3	4	1	3	2
≥ 1 Severe TEAE	0	0	0	0	0
≥ 1 Serious TEAE	0	0	0	0	0
Study Drug Discontinuation Due to TEAE	0	0	0	0	0

Population analysed: Safety Analysis Set

Primary outcome: Change From Baseline to the End of Treatment (Day 15) in Serum Bicarbonate Within Each Individual TRC101 Dose Group

Time frame: Baseline and Day 15. Least squares mean (Standard Error). Unit: mEq/L

Measure	Pooled Placebo n = 31	1.5g TRC101 BID n = 25	3g TRC101 BID n = 25	4.5g TRC101 BID n = 26
Value	-0.2 (0.4)	3.2 (0.4)	3.0 (0.4)	3.7 (0.4)

Pooled Placebo: Group LS mean: -0.2 (95% CI -0.9 to 0.5), p = 0.5547, Mixed Models Analysis
1.5g TRC101 BID: Group LS mean: 3.2 (95% CI 2.4 to 4.0), p < 0.0001, Mixed Models Analysis
3g TRC101 BID: Group LS mean: 3.0 (95% CI 2.2 to 3.8), p < 0.0001, Mixed Models Analysis

Population analysed: Full Analysis Set

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Through treatment period completion (Day 15). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pooled Placebo	0 of 31 (0%)	12 of 31 (38.7%)	0 of 31
1.5g TRC101 BID	0 of 25 (0%)	13 of 25 (52%)	0 of 25
3g TRC101 BID	0 of 25 (0%)	9 of 25 (36%)	0 of 25
4.5g TRC101 BID	0 of 26 (0%)	17 of 26 (65.4%)	0 of 26
6g TRC101 QD	0 of 28 (0%)	13 of 28 (46.4%)	0 of 28

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 29102959Bushinsky 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Yuri Stasiv, PhD study director

Tricida, Inc.

5 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TRC101 in people with Acidosis, run by Tricida, Inc. at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Georgia, Bulgaria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Number of Subjects Who Discontinued Study Drug Due to a TEAE (time frame: Through treatment period completion (Day 15)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02809183, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2020.