Trial Outcomes & Findings for Evaluation of TRC101 in Subjects With Metabolic Acidosis Associated With Chronic Kidney Disease (NCT NCT03317444)

Last Updated: 2021-04-26

Results Overview

Composite endpoint of the percentage of subjects having a change from baseline in serum bicarbonate ≥ 4 mEq/L or having serum bicarbonate in the normal range (22 - 29 mEq/L) at the end of treatment (Week 12 Visit).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

217 participants

Primary outcome timeframe

Baseline to Week 12

Results posted on

2021-04-26

Participant Flow

Participant milestones

Participant milestones
Measure	TRC101 Treatment Arm The first dose of blinded study drug (2 packets for a total of 6 g TRC101) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, TRC101 was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 3 or 9 g (0, 1 or 3 packets, respectively) of TRC101 QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.	Placebo Treatment Arm The first dose of blinded study drug (2 packets of placebo) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, placebo was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 1 or 3 packets of placebo QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.
Overall Study STARTED	124	93
Overall Study COMPLETED	119	89
Overall Study NOT COMPLETED	5	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TRC101 Treatment Arm n=124 Participants The first dose of blinded study drug (2 packets for a total of 6 g TRC101) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, TRC101 was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 3 or 9 g (0, 1 or 3 packets, respectively) of TRC101 QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.	Placebo Treatment Arm n=93 Participants The first dose of blinded study drug (2 packets of placebo) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, placebo was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 1 or 3 packets of placebo QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.	Total n=217 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	59 Participants n=5 Participants	44 Participants n=7 Participants	103 Participants n=5 Participants
Age, Categorical >=65 years	65 Participants n=5 Participants	49 Participants n=7 Participants	114 Participants n=5 Participants
Age, Continuous	62.9 years STANDARD_DEVIATION 12.64 • n=5 Participants	63.3 years STANDARD_DEVIATION 12.08 • n=7 Participants	63.1 years STANDARD_DEVIATION 12.38 • n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	33 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	60 Participants n=7 Participants	134 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	121 Participants n=5 Participants	89 Participants n=7 Participants	210 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
History of Hypertension	120 Participants n=5 Participants	90 Participants n=7 Participants	210 Participants n=5 Participants
History of Diabetes Mellitus	76 Participants n=5 Participants	65 Participants n=7 Participants	141 Participants n=5 Participants
History of Congestive Heart Failure	36 Participants n=5 Participants	31 Participants n=7 Participants	67 Participants n=5 Participants
Baseline Estimated Glomerular Filtration Rate (eGFR)	29.2 mL/min/1.73m^2 STANDARD_DEVIATION 6.29 • n=5 Participants	27.8 mL/min/1.73m^2 STANDARD_DEVIATION 5.45 • n=7 Participants	28.6 mL/min/1.73m^2 STANDARD_DEVIATION 5.97 • n=5 Participants
Baseline Bicarbonate	17.27 mEq/L STANDARD_DEVIATION 1.429 • n=5 Participants	17.30 mEq/L STANDARD_DEVIATION 1.504 • n=7 Participants	17.28 mEq/L STANDARD_DEVIATION 1.458 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 12

Population: The Modified Intent-to-Treat (MITT) Analysis Set was defined as all randomized subjects who had both baseline and at least one postbaseline serum bicarbonate value measured using an i-STAT device. The MITT Analysis Set was used for evaluation of efficacy, based on planned treatment assignment.

Outcome measures

Outcome measures
Measure	TRC101 Treatment Arm n=120 Participants The first dose of blinded study drug (2 packets for a total of 6 g TRC101) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, TRC101 was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 3 or 9 g (0, 1 or 3 packets, respectively) of TRC101 QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.	Placebo Treatment Arm n=89 Participants The first dose of blinded study drug (2 packets of placebo) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, placebo was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 1 or 3 packets of placebo QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.
Subjects With Change From Baseline in Serum Bicarbonate of ≥ 4 mEq/L or Serum Bicarbonate Within the Normal Range Subjects with change from baseline serum bicarbonate ≥ 4 mEq/L or serum bicarbonate in normal range	59.2 percentage of participants Interval 49.8 to 68.0	22.5 percentage of participants Interval 14.3 to 32.6
Subjects With Change From Baseline in Serum Bicarbonate of ≥ 4 mEq/L or Serum Bicarbonate Within the Normal Range Subjects with change from baseline serum bicarbonate ≥ 4 mEq/L	55.8 percentage of participants Interval 46.5 to 64.9	21.3 percentage of participants Interval 13.4 to 31.3
Subjects With Change From Baseline in Serum Bicarbonate of ≥ 4 mEq/L or Serum Bicarbonate Within the Normal Range Subjects with serum bicarbonate in normal range	50.0 percentage of participants Interval 40.7 to 59.3	16.9 percentage of participants Interval 9.8 to 26.3

SECONDARY outcome

Timeframe: Baseline to Week 12

Mean change from baseline to end of treatment (Week 12 Visit) in serum bicarbonate

Outcome measures

Outcome measures
Measure	TRC101 Treatment Arm n=123 Participants The first dose of blinded study drug (2 packets for a total of 6 g TRC101) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, TRC101 was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 3 or 9 g (0, 1 or 3 packets, respectively) of TRC101 QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.	Placebo Treatment Arm n=93 Participants The first dose of blinded study drug (2 packets of placebo) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, placebo was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 1 or 3 packets of placebo QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.
Change From Baseline to End of Treatment in Serum Bicarbonate	4.42 mEq/L Interval 3.85 to 4.98	1.78 mEq/L Interval 1.13 to 2.44

Adverse Events

TRC101 Treatment Arm

Serious events: 3 serious events

Other events: 31 other events

Deaths: 0 deaths

Placebo Treatment Arm

Serious events: 2 serious events

Other events: 13 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	TRC101 Treatment Arm n=124 participants at risk The first dose of blinded study drug (2 packets of TRC101 \[6 g\]) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, TRC101 was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 3 or 9 g (0, 1 or 3 packets, respectively) of TRC101 QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.	Placebo Treatment Arm n=93 participants at risk The first dose of blinded study drug (2 packets of placebo) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, placebo was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 1 or 3 packets of placebo QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.
Injury, poisoning and procedural complications Fall	0.81% 1/124 • Number of events 1 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.	0.00% 0/93 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.
Cardiac disorders Angina unstable	0.00% 0/124 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.	1.1% 1/93 • Number of events 1 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.
Cardiac disorders Acute left ventricular failure	0.81% 1/124 • Number of events 1 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.	0.00% 0/93 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.
Cardiac disorders Cardiac failure congestive	0.81% 1/124 • Number of events 1 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.	0.00% 0/93 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.
Nervous system disorders Diabetic hyperglycaemic coma	0.00% 0/124 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.	1.1% 1/93 • Number of events 1 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.
General disorders Asthenia	0.81% 1/124 • Number of events 1 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.	0.00% 0/93 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.
Renal and urinary disorders Acute kidney injury	0.81% 1/124 • Number of events 1 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.	0.00% 0/93 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.
Infections and infestations Pneumonia	0.00% 0/124 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.	1.1% 1/93 • Number of events 1 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.

Other adverse events

Other adverse events
Measure	TRC101 Treatment Arm n=124 participants at risk The first dose of blinded study drug (2 packets of TRC101 \[6 g\]) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, TRC101 was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 3 or 9 g (0, 1 or 3 packets, respectively) of TRC101 QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.	Placebo Treatment Arm n=93 participants at risk The first dose of blinded study drug (2 packets of placebo) was given at the study site on Day 1 in the morning with food. For the remainder of the Treatment Period, placebo was self-administered orally as an aqueous suspension, QD with lunch, for 12 weeks. Beginning at the Week 4 Visit, subjects could have had a blinded dose adjustment to 0, 1 or 3 packets of placebo QD in accordance with a protocol-specified titration algorithm. The last dose of study drug was to be taken the day before the Week 12 Visit, unless the subject was enrolled in the extension Study TRCA-301E.
Nervous system disorders Headache	5.6% 7/124 • Number of events 7 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.	4.3% 4/93 • Number of events 5 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.
Gastrointestinal disorders Diarrhoea	8.9% 11/124 • Number of events 20 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.	3.2% 3/93 • Number of events 6 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.
Metabolism and nutrition disorders Hyperkalaemia	10.5% 13/124 • Number of events 16 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.	6.5% 6/93 • Number of events 6 • Data are the number of patients with adverse events occurring on or after the date of the first dose of TRC101 or placebo up to 14 weeks.

Additional Information

Medical Information

Tricida, Inc.

Phone: 415-429-7800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place