- Statistically significant 39 percent reduction in mean joint pain score in hip patients at eight weeks with 5.0 mg dose -
- 35 percent reduction in mean joint pain score for all patients at eight weeks with 5.0 mg dose -
- All tablet strengths well tolerated over eight-week treatment period -
- Conference call today at
"Developing effective analgesics that lack the high abuse potential and serious side effects of currently available drug classes remains the most pressing need in chronic pain," said Dr.
Oral CR845 Phase 2b Trial Design and Results
The Phase 2b trial was a randomized, double-blind, placebo-controlled trial of three tablet strengths of CR845, 1.0 mg, 2.5 mg and 5.0 mg, dosed twice a day (BID) over an eight-week treatment period in 476 patients with osteoarthritis of the hip or knee experiencing moderate-to-severe pain.
- The primary efficacy endpoint was the change from baseline at week eight, with respect to the weekly mean of the daily pain intensity score using a numerical rating scale (NRS).
- Secondary endpoints included overall Patient Global Assessment (PGA) score, mean reduction in rescue medication and overall improvement in WOMAC scores.
- The trial design incorporated a four-week titration period for a response, followed by a four-week maintenance period. Sixty-seven percent of CR845-treated patients in the maintenance period titrated to the 5.0 mg dose after the four-week titration period, based on change in the observed mean joint pain score (NRS).
- Patients with OA of the hip maintained on the 5.0 mg dose to the end of the eight-week treatment period exhibited a statistically significant 39 percent reduction in mean joint pain score (p=0.043 vs. placebo); all patients (OA of the knee or hip) maintained on the 5.0 mg dose to the end of the eight-week treatment period exhibited a 35 percent reduction in mean joint pain score (p=0.111 vs. placebo).
- Patients maintained on the 1.0 mg and 2.5 mg tablet strengths did not exhibit significant reductions in mean joint pain scores compared to placebo.
- For patients maintained on the 5.0 mg dose, there was a statistically significant increase in the proportion of patients whose OA was "very much improved" or "much improved" as indicated by Patient Global Assessment score in both the total patient group (p < 0.005 vs. placebo) and in patients with primary OA of the hip (p < 0.006 vs. placebo).
- The reduction in pain score in the 5.0 mg dose group in hip patients was accompanied by a reduction in mean rescue medication of 41 percent at week eight versus placebo.
- An overall improvement of 62 percent from baseline in WOMAC scores was observed over the eight-week treatment period for the 5.0 mg dose group in hip patients.
- All tablet strengths were generally well tolerated with no drug-related serious adverse events (SAEs). For the 5.0 mg dose, the most common adverse events reported at the > 5 percent incidence level were dry mouth (six percent) and constipation (12 percent). Importantly, there were no clinically significant changes in serum sodium levels observed during the eight-week treatment period for any dose group.
"We believe that the present trial of oral CR845 has highlighted the potential of a peripherally acting kappa agonist to provide clinical benefit in a chronic pain population and we're pleased that statistical significance was achieved for the 5.0 mg dose in patients with OA of the hip," said
Conference Call
Cara management will host a conference call today at 4:30 p.m. ET to discuss the Oral CR845 OA trial results and next steps for the program. To participate in the conference call, please dial (855) 445-2816 (domestic) or (484) 756-4300 (international) and refer to conference ID 47802588. A live webcast of the call can be accessed under "Events and Presentations" in the News & Investors section of the Company's website at www.CaraTherapeutics.com.
An archived webcast recording will be available on the Cara website beginning approximately two hours after the call.
About CR845
CR845 is a peripherally acting kappa opioid receptor agonist currently in development for the treatment of acute and chronic pain and pruritus. In multiple randomized, double-blind, placebo-controlled Phase 2 trials in patients undergoing laparoscopic hysterectomy or bunionectomy procedures, I.V. CR845 treatment resulted in statistically significant reductions in pain intensity and opioid-related side effects. In more than 1200 subjects dosed to date, CR845 was observed to be well-tolerated, without incurring the dysphoric and psychotomimetic side effects that have been reported with centrally acting (CNS-active) kappa opioid receptor agonists, and lacking the respiratory depression and abuse liability of mu opioid receptor agonists.
About
Forward-looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Examples of
these forward-looking statements include statements concerning oral CR845's potential to treat chronic pain patients and expand the potential clinical utility of CR845 beyond acute pain, the establishment of the clinical utility of Oral CR845 and the future clinical development of Oral CR845, including the expected timing and design of any additional clinical trial(s). Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in
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