- Limited number of asymptomatic, transient rises in serum sodium triggers pre-specified safety review and protocol clinical hold
- No CR845-associated serious adverse events (SAEs) observed to date
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Conference call today at 4:30 p.m. ET
SHELTON, Conn., Feb. 25, 2016 (GLOBE NEWSWIRE) -- Cara Therapeutics, Inc. (NASDAQ:CARA), a biotechnology company focused on developing and commercializing new chemical entities designed to alleviate pain and pruritus by selectively targeting kappa opioid receptors, today announced that it has received oral notification from the U.S. Food and Drug Administration (FDA) that its adaptive pivotal trial of I.V. CR845 for postoperative pain has been placed on protocol clinical hold pending a pre-specified safety review. A protocol-specified stopping rule, based on elevated serum sodium levels greater than 150 mmol/L, was met during the first phase of the study, and a review of unblinded safety data has been undertaken by both Cara and the Independent Data Monitoring Committee (IDMC) in accordance with the protocol. The initial results of this safety data review show:
- Out of 90 total patients dosed to date, four patients in the highest CR845 dose group (5 ug/kg) exhibited transient serum sodium levels equal to or greater than 150 mmol/L (mild-to-moderate hypernatremia). All four patients were asymptomatic and sodium levels resolved to normal levels (<146 mmol/L) within 24 hours post-dosing with standard fluid management. No patients in the other two dose groups — 2 ug/kg and 1 ug/kg — exhibited serum sodium levels greater than 150 mmol/L.
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The most common adverse events (> 5%) reported across treatment groups and placebo so far were nausea, hypernatremia, abdominal distension and procedural hypotension. All cases of abdominal distension and procedural hypotension were attributed to the surgical procedure and not to study drug. There were no cases of respiratory depression, no adverse events greater than Grade 1, and no CR845-associated serious adverse events have been reported.
"We are working closely with the FDA to review patient safety data and resolve this issue in a timely manner," said Derek Chalmers, Ph.D., D.Sc., President and Chief Executive Officer of Cara Therapeutics. "We remain very confident in the overall efficacy and safety profile of I.V. CR845 in the treatment of postoperative pain, and are encouraged that there have been no serious CR845-related adverse events so far in our Phase 3 program. We look forward to continuing the study, pending FDA review, as we work to bring this novel class of therapeutics to patients in need of additional pain treatment options."
The CLIN3001 study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group adaptive design Phase 3 trial with repeated doses of I.V. CR845 or placebo administered both prior to and following abdominal surgery in male and female patients. The trial is enrolling up to 600 patients undergoing either hysterectomy, prostatectomy, hemi-colectomy or ventral hernia repair at 30 clinical sites within the U.S. Three doses of I.V. CR845 (1.0, 2.0 and 5.0 ug/kg I.V.) are being compared to placebo. The primary efficacy measure is the Change in Pain Intensity over the 24-hour postoperative period (AUC-24) using the patient-reported Numeric Rating Scale (NRS) score collected at pre-specified time points through 24 hours. Postoperative nausea and vomiting (PONV), which were reduced in previous clinical trials of I.V. CR845, are being evaluated as a secondary efficacy measure. Based on ex vivo reductions in inflammatory biomarkers in synovial joint cells from patients with inflammatory disease, the impact of CR845 treatment on these biomarkers is also being explored.
Conference Call
Cara management will host a conference call today at 4:30 p.m. ET to discuss the ongoing safety review for CLIN3001.
To participate in the conference call, please dial 855-445-2816 (domestic) or 484-756-4300 (international) and refer to conference ID 60305319. 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 both pain intensity and opioid-related side effects. In 495 subjects dosed to date, I.V. CR845 was found 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. Cara initiated its Phase 3 Program of I.V. CR845 for acute pain with a first adaptive pivotal trial in laparoscopic abdominal surgery in 3Q'15.
About Cara Therapeutics
Cara Therapeutics is a clinical-stage biotechnology company focused on developing and commercializing new chemical entities designed to alleviate pain and pruritus by selectively targeting kappa opioid receptors. Cara is developing a novel and proprietary class of product candidates that target the body's peripheral nervous system and have demonstrated efficacy in patients with moderate-to-severe pain without inducing many of the undesirable side effects typically associated with currently available pain therapeutics.
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 the ongoing safety review related to the trial of I.V. CR845 and the potential removal of the protocol clinical hold and resumption of the trial. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks include risks that the company may be unable to obtain a release of the protocol clinical hold, that the FDA may elevate the protocol clinical hold to a full clinical hold, as well as those risks described more fully in Cara Therapeutics' filings with the Securities and Exchange Commission, including the "Risk Factors" section of the Company's Annual Report on Form 10-K for the year ended December 31, 2014, the Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and its other documents subsequently filed with or furnished to the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Cara Therapeutics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
CORPORATE CONTACT: Derek Chalmers, Ph.D., D.Sc. President & CEO Cara Therapeutics, Inc. 203-567-1500 MEDIA CONTACT: Annie Starr 6 Degrees 973-415-8838 [email protected] INVESTOR CONTACT: Jesse Baumgartner Stern Investor Relations, Inc. 212-362-1200 [email protected]