Industry Briefs

Tramadol Appears to Be Less Effective as Adjunctive Therapy for MDD Than Amitriptyline

E-Therapeutics plc last month announced disappointing results for its phase 2b trial of ETS6103, a controlled-released version of the analgesic tramadol. The trial was evaluating the medication as second-line therapy for patients with major depressive disorder (MDD) who have not responded adequately to first-line therapy with a selective serotonin reuptake inhibitor.

The study included 164 patients with MDD who continued to report significant depressive symptoms after six weeks on citalopram. The participants were randomized into one of three study arms: one arm received a high dose of ETS6103, a second received a low dose of ETS6103, and a third received one dose of tricyclic amitriptyline. Patients were dosed once daily over an eight-week period.

The results showed that both ETS6103 arms failed overall to achieve the primary endpoint of being as effective as amitriptyline in achieving remission of depressive symptoms, based on obtaining a score of 11 or lower on the Montgomery–Åsberg Depression Rating Scale.

The company plans to further analyze the data and provide a full update of the phase 2b trial by the end of the month.

FDA Puts Hold on Trial of Potential Abuse-Deterrent Painkiller

Last week, Cara Therapeutics Inc. announced that the Food and Drug Administration has placed the company’s phase 3 clinical trial of the postoperative intravenous analgesic CR845 on hold pending a safety review.

The trial was stopped, in accordance with the protocol, after four patients in the highest R845 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 (less than 146 mmol/L) within 24 hours postdosing 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.

Previous phase 2 clinical trials with CR845 found the medication to reduce postoperative pain intensity and opioid-related side effects in patients who underwent laparoscopic hysterectomy or bunionectomy procedures; it also had a lower potential to be abused than the opioid painkiller pentazocine. CR845 targets the kappa opioid receptor. ■