Tricida Announces Publication of Positive TRC101 Pivotal Trial Results in The Lancet
“TRC101 substantially increased blood bicarbonate levels in the TRCA-301
“The publication of our Phase 3 TRC101 clinical trial results in The
Lancet, a leading independent general medical journal, is an
important milestone for
Results from the TRCA-301 clinical trial were previously presented at
Primary and Secondary Endpoints Met with High Statistical Significance
The TRCA-301 clinical trial achieved both its prespecified primary and secondary endpoints. After 12 weeks of treatment, the primary endpoint, the proportion of patients achieving a ≥4 mEq/L increase from baseline in blood bicarbonate at Week 12 or a blood bicarbonate in the normal range, was met by 59.2% of patients in the TRC101-treated group compared to 22.5% of patients in the placebo group (p<0.0001). The secondary endpoint, the least squares (LS) mean blood bicarbonate increase from baseline to Week 12 was 4.4 mEq/L (TRC101) vs. 1.8 mEq/L (placebo) (p<0.0001).
Promising Data from Prespecified Exploratory Physical Functioning Endpoints
Because of the potential for adverse effects of acidosis on muscle, two measures of physical functioning were evaluated as prespecified exploratory endpoints in the trial. The first exploratory endpoint examined the effect of treatment with TRC101 on self-reported responses to the 10-question SF-36 Physical Function subscale of the Kidney Disease and Quality of Life survey, which quantifies patients’ reported degree of limitation in performing daily activities such as climbing stairs and walking. The second exploratory endpoint objectively measured physical functioning, assessed using a repeated chair stand test involving a timed measurement of five repetitions of moving from a seated to standing position.
At Week 12, self-reported physical functioning increased significantly in TRC101-treated patients compared to placebo-treated patients (p = 0.0122). At the end of 12 weeks of treatment, physical functioning, as measured objectively by the repeated chair stand test, numerically improved in the TRC101 group (p = 0.0249) and numerically worsened in the placebo group (p = 0.5727), but the between-group difference was not statistically significant (p = 0.0630). As the physical functioning results were not normally distributed, post-hoc rank-based statistical analyses were conducted and showed consistent results for patient-reported physical function (p=0.0117) and a stronger association for the between-group difference in the time to complete the repeated chair stand test (p=0.0027), both favoring TRC101.
Safety Profile Assessed
Dosing compliance, defined as ≥80% of doses administered, was >98%. The overall safety profile of TRC101 observed in the trial was consistent with that expected for the general population of patients with Stage 3 to 5 CKD and with similar non-absorbed polymer drugs with a site of action in the gastrointestinal tract. There were two deaths in the study and both occurred in the placebo group. The incidence of serious adverse events was low and balanced between the two arms and none were considered related to study drug by the site investigators or occurred in more than one patient. The most common body system in which adverse events in the TRC101 group occurred was gastrointestinal; of these, non-treatment limiting diarrhea was the most common event: 11 (9%) versus 3 (3%) in the TRC101 and placebo groups, respectively. The most common treatment-related adverse events were also in the gastrointestinal system, occurring in 5 (5%) patients in the placebo group and 16 (13%) in the TRC101-treated group, and most of these were mild or moderate. Treatment-related gastrointestinal adverse events that occurred in more than one subject were diarrhea, flatulence, nausea and constipation. Over 95% of the patients in each group completed the trial.
TRCA-301 Clinical Trial Design
Phase 3, multicenter, parallel, randomized, double-blind,
placebo-controlled trial, TRCA-301, was conducted at 37 sites in
Eligible patients who completed the TRCA-301 trial were invited to participate in a 40-week safety extension trial, TRCA-301E. Of the 208 patients who completed the TRCA-301 trial, 196 were enrolled in the TRCA-301E safety extension trial.
In addition to Dr. Wesson, study authors included:
Metabolic acidosis is estimated to pose a health risk to approximately
three million patients with CKD in
Metabolic acidosis in patients with CKD has traditionally been treated with sodium-based alkali supplements that enter the systemic circulation and neutralize accumulated acid. Alternative treatments for metabolic acidosis include vegetarian diets, but these limit patient choice and have low long-term adherence issues. An alternative potential treatment would remove, rather than neutralize, acid, without administering a sodium load. Removal of acid by binding it to a non-absorbed polymer, such as TRC101, then excreting it, is a potential first-in-class treatment of metabolic acidosis in patients with CKD.
For more information about
Cautionary Note on Forward-Looking Statements
This press release includes forward-looking statements, including for
example, statements about our ability to submit an NDA for TRC101 under
the FDA’s Accelerated Approval Program. Forward‐looking statements
involve known and unknown risks, uncertainties, assumptions and other
factors that may cause our actual results, performance or achievements
to be materially different from any future results, performance or
achievements expressed or implied by the forward‐looking
statements. These risks and uncertainties include, among others, include
the timing of Tricida’s NDA submission; that many drug candidates that
have completed Phase 3 trials do not become approved drugs on a timely
or cost effective basis or at all; there can be no assurance that the
Jackie Cossmon, IRC
Vice President of Investor Relations and Communications