CARA Cara Therapeutics Inc

On December 3, 2019, the Company issued a press release announcing top-line data from its Phase 2 clinical trial of Oral KORSUVA for CKD-aP.

The Phase 2, multicenter, randomized, double-blind, placebo-controlled 12-week trial was designed to evaluate the safety and efficacy of three tablet strengths (0.25 mg, 0.5 mg and 1 mg, once daily administration) of Oral KORSUVA versus placebo in approximately 240 stage III-V (moderate to severe) CKD patients with moderate-to-severe pruritus. The primary efficacy endpoint was the change from baseline in the weekly mean of the daily 24-hour worst itch Numeric Rating Scale (“WI-NRS”) score at Week 12 of the treatment period. Secondary endpoints included change from baseline in itch-related quality of life scores at the end of Week 12, as assessed by the total Skindex-10 and 5-D itch scores, as well as the proportion of patients achieving an improvement from baseline ≥3 points with respect to the weekly mean of the daily 24-hour WI-NRS score at Week 12.

Primary Endpoint: Patients treated with the 1 mg once daily tablet strength of Oral KORSUVA achieved the primary endpoint of statistically significant reduction in weekly mean of the daily WI-NRS scores versus placebo after the 12-week treatment period (-4.4 KORSUVA vs. -3.3 placebo, p=0.018). The treatment effect was statistically significant after 2 weeks of treatment and sustained through the 12-week treatment period.

Secondary Endpoints:

Proportion of Responders. The proportion of patients on 1 mg tablet strength achieving a 3 point or greater improvement from baseline in the weekly mean of the daily WI-NRS score at Week 12 was 72% versus 58% for patients on placebo but did not achieve statistical significance.

Itch-Related Quality of Life Measures. Patients on Oral KORSUVA showed dose-related improvements vs. placebo in itch-related quality of life endpoints as measured using self-assessment Skindex-10 and 5-D Itch scales but did not achieve statistical significance.

Safety and Tolerability: Oral KORSUVA was generally well tolerated with a safety profile consistent with that seen in earlier KORSUVA clinical trials. Overall, the incidence of treatment-emergent adverse events (“AEs”) were similar across KORSUVA and placebo groups. The most common treatment-emergent AEs reported in >5% of patients in the 1 mg KORSUVA group versus placebo were dizziness (7.5% KORSUVA vs. 0% placebo), fall (6% KORSUVA vs. 0% placebo), diarrhea (6% KORSUVA vs. 1.5% placebo) and constipation (KORSUVA 6% vs. 3% placebo).