Data from Pharmawand - Curated by EPG Health - Date added 06 June 2018
Tricida announced results from its pivotal Phase III double-blind, randomized, placebo-controlled, multi-center Phase III clinical trial, TRCA 301, in 217 chronic kidney disease (CKD) patients with metabolic acidosis. Based on the initial topline analyses, the TRCA-301 trial met both its primary and secondary endpoints in a highly statistically significant manner (p < 0.0001 for all primary and secondary endpoints). TRC101 was well tolerated in the TRCA-301 trial. Both active (124 subjects) and placebo groups (93 subjects) had low discontinuation rates and low rates of treatment-related adverse events.
For the primary endpoint, after 12 weeks of treatment, 59.2% of subjects in the TRC101 treatment group exhibited an increase in blood bicarbonate level of at least 4 milliequivalents per liter (mEq/L) or achieved a blood bicarbonate level in the normal range of 22 to 29 mEq/L, compared with 22.5% of subjects in the placebo group (p< 0.0001). For the secondary endpoint, the mean change in blood bicarbonate from baseline to week 12, subjects in the TRC101 treatment group exhibited a mean increase in blood bicarbonate of 4.49 mEq/L, compared with 1.66 mEq/L in the placebo group (p<0.0001). In addition, two pre-specified exploratory endpoints of the pivotal Phase III TRCA-301 trial assessed patient quality of life and improvement in muscle function. The first exploratory endpoint examined the effect of treatment with TRC101 on self-reported responses to the physical functioning subpart of the Kidney Disease and Quality of Life Short Form survey (KDQOL-SF survey).
The second exploratory endpoint objectively measured physical function, assessed using a repeated chair stand test, involving a timed measurement of five repetitions of moving from a seated to standing position. Initial topline analyses of the results of the physical functioning KDQOL-SF survey showed a statistically significant positive difference in the TRC101-treated subjects compared with the placebo group after 12 weeks of treatment (p=0.0122) and the repeated chair stand test showed a trend toward significance in the positive difference in the TRC101-treated subjects compared with the placebo group (p=0.0630).
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. The incidence of serious adverse events was low and balanced in the two treatment groups and none were assessed to be related to TRC101 by the clinical investigator, Medical Monitor or Drug Safety and Pharmacovigilance Team. There were two deaths in the study and both occurred in the placebo group. Overall treatment-related adverse events occurred in 9.7% of subjects in the placebo group and 13.7% of the TRC101-treated subjects. Treatment-related gastrointestinal adverse events that occurred in more than one subject include diarrhea, flatulence, nausea and constipation. Over 95% of the subjects in each group completed the trial.0>