Trevena, Inc. announced the initiation of a Phase 2b clinical trial of TRV130 for acute postoperative pain in patients following abdominoplasty surgery. TRV130 is a small molecule biased ligand at the mu-opioid receptor that Trevena is developing as a first-line intravenous treatment for patients experiencing moderate-to-severe acute pain. In this multicenter, randomized, double-blind, placebo- and active-controlled clinical trial, TRV130's efficacy and tolerability will be evaluated in the management of postoperative pain following abdominoplasty surgery, a representative soft tissue surgery.

The study will include morphine as a benchmark and utilize a flexible dose, patient-controlled analgesia (PCA) administration regimen intended to optimize treatment and reflect the as-needed dosing most commonly used with post-operative opioid analgesics. Approximately 200 patients will be assigned randomly to a post-operative regimen of TRV130, placebo, or morphine, in a 2:1:2 ratio respectively, for 24 hours after surgery, beginning when post-operative pain becomes moderate or severe in intensity. Treatment in the study will begin with a double-blind loading dose of TRV130, morphine or placebo, after which each patient can self-administer lower doses as needed for pain relief.

This allows patients to increase dosing if analgesia is insufficient and to limit dosing if side effects are intolerable. After the first hour of treatment, the investigator may increase the strength of the available patient-administered dose by 50% in a double-blind fashion if additional pain relief is needed. The primary endpoint of this study is the time-weighted average change from baseline in the numeric pain rating scale scores over the 24-hour assessment interval for TRV130 compared to placebo.

TRV130 will be compared to morphine as a secondary endpoint. Other secondary assessments include evaluation of pain scores over shorter assessment intervals; rates of opioid-related adverse effects as measured by oxygen saturation, nausea numeric rating scale, and rescue antiemetic utilization; and patient satisfaction using the Patient Global Assessment of the Method of Pain Control. This study will progress in parallel with the Companyâ s ongoing preparations for Phase 3 clinical trials of TRV130, which are expected to begin in the first quarter of 2016.

Top-line data from this Phase 2 study are expected in mid-2015. TRV130 was designed to optimize opioid receptor pharmacology to deliver an improved analgesic profile. TRV130 is a biased mu-opioid receptor ligand, a novel opioid receptor modulator which in preclinical studies activated analgesic signals while avoiding signals that can interfere with analgesia and promote respiratory depression and gastrointestinal dysfunction.

The company recently reported top-line data for a Phase 2a/b trial comparing TRV130 to placebo and morphine following bunionectomy surgery. In this trial TRV130 demonstrated superior efficacy to a standard dose of morphine, with average reduction in numeric pain rating scale up to 6 points from a baseline of 7 points. This efficacy was achieved without any serious adverse events and without significant respiratory depression as measured by oxygen desaturation.

Trends in respiratory depression were worse for morphine than for TRV130. Doses of TRV130 that showed superior efficacy to morphine had similar tolerability to morphine. Trevena believes that TRV130 may have an improved profile compared to currently used opioid analgesics and could offer enhanced pain relief with a reduced burden of opioid-related adverse events.

Trevena anticipates that the initial market opportunity for TRV130 will be in the acute care settings, with a focus on postoperative pain in the hospital.