The agency placed the hold last month after elevated serum sodium levels were found in four patients who received the highest dose of 5 ug/kg.
Cara Therapeutics’ analysis confirmed that the excess sodium levels in the blood were dose-dependent and asymptomatic, with the lowest frequency of events identified in the 1 ug/kg cohort.
The trial will now continue with three arms: 0.5 ug/kg, 1.0 ug/kg and placebo, removing the 5 ug/kg dose.
Cara Therapeutics president and CEO Derek Chalmers said: "Our unblinded analysis of the initial cohort of patients has identified interim efficacy signals for pain, supplemental opioid use and opioid-related side effects that support our dose selections.
"We look forward to continuing patient recruitment next month and to providing further updates on our progress later this year."
The study, CLIN3001, will enroll up to 450 patients undergoing either hysterectomy, prostatectomy, hemi-colectomy or ventral hernia repair.
The primary endpoint is the change in pain intensity over 24 hours after surgery as measured by the patient-reported numeric rating scale. Postoperative nausea and vomiting will be assessed as a secondary measure.
CR845 is a peripherally acting kappa opioid receptor agonist being developed to treat acute and chronic pain and pruritus.
I.V. CR845 treatment reduced pain intensity and opioid-related side effects in several randomized, double-blind, placebo-controlled phase 2 trials in patients undergoing laparoscopic hysterectomy or bunionectomy procedures.