Robert H. Spencer

Poster 147 CR845, a Peripheral Kappa Opioid Receptor Agonist, Provides Better Pain Relief With Less Nausea and Vomiting Than Placebo in Patients After Bunionectomy

Disclosures: J. W. Stauffer: Employment Cara Therapeutics, Inc. Objective: To assess the analgesic efficacy of CR845, a peripherallyacting, selective kappa opioid receptor agonist. Design: Double-blind, placebo-controlled clinical study. Setting: Single-center clinical research organization. Participants: Adult patients (N1⁄451) undergoing elective primary unilateral first metatarsal bunionectomy surgery. Interventions: One day after bunionectomy, patients were randomized 2:1 to CR845 (5 mcg/kg, IV) or placebo after reporting a Visual Analogue Scale (VAS) pain score 40 (out of 100) at rest. Within 30-60 minutes after the initial study drug dose, patients could receive an additional dose, as needed, and then every 8 hours as needed over the next 48 hours. Rescue medication (fentanyl 50 mcg IV) was available as needed. Main Outcome Measures: Pain intensity (VAS) was assessed periodically during the 48-hour study period. The mean summed pain intensity differences from baseline over 24 hours (SPID0-24) was the primary efficacy measurement. Results or Clinical Course: In the prespecified analysis of the completer population, a statistically significant reduction in SPID0-24 with CR845 compared to placebo (P 1⁄4.033) was observed, with only CR845 having a 95% CI significantly less than 0 (P 1⁄4.0007). This observation was supported using the modified intent-to-treat population in which a greater decrease in SPID0-24 was observed with CR845 than placebo, although this difference was not significant (P 1⁄4.116). Again, only CR845 had a 95% CI significantly less than 0 (P 1⁄4.022). The SPID0-48 difference between treatment groups was statistically significant for the completer population (P 1⁄4.024). Compared to placebo, patients treated with CR845 experienced fewer treatment-emergent adverse events (AEs) of nausea (23.6% vs. 58.8% for placebo; P 1⁄4.028) and vomiting (5.9% vs. 23.9% for placebo; P 1⁄4.034). Mild transient facial tingling (paresthesia) and somnolence were observed with CR845 (11.8% for both), but there were no reports of psychiatric AEs characteristic of centrally-acting kappa opioids. Conclusion: In this study, CR845 resulted in reduced pain intensity with lower incidence of nausea and vomiting versus placebo in patients after bunionectomy surgery. Sponsored by: Cara Therapeutics, Inc.

Poster 146 CR845, a Novel Peripherally-Acting Kappa Opioid Receptor Agonist, Has Low Abuse Potential Compared With Pentazocine

Disclosures: D. Park: I Have No Relevant Financial Relationships To Disclose. Objective: To determine the effects of graded lumbar stabilization exercises on lumbar stabilizing muscles. Design: Cross-sectional study. Setting: Tertiary teaching hospital. Participants: Ten healthy males. Interventions: Five common exercises for strengthening the lumbar stabilizing muscles were selected: curl up, dead bug, side bridge, superman and bird dog exercises. And each exercise was divided into five levels by varied level of intensity. Main Outcome Measures: Using superficial electromyography, the electrical activity of rectus abdominis (RA), external oblique abdominis (EO), multifidus (MF) and erector spinae (ES) muscles was recorded during the exercise. The areas under the curve which were adjusted to different duration and peak amplitude were calculated. The Kruskal Wallis test and the post-hoc test with Mann-Whitney test were used. Results or Clinical Course: As the level of intensity of each exercise increased, the activity of related lumbar stabilizing muscles was generally increased. In detail, the activity of RA and EO was distinctly increased when trunk curl was added to neck flexed or supine position in the curl up exercise. However the posture of upper extremities didn’t influence the activity change of recorded lumbar stabilizing muscles. In the dead bug posture, the activities of RA, EO and MF were more increased while performing both arm and leg movements rather than arm or leg movement alone. In the side bridge posture, when leg abduction was added, mean area of MF was significantly increased. In the prone posture, lengthening the duration of the superman exercise increased the mean area of MF, ES and RA. In the bird dog posture, the activities of ES and MF were more increased while performing both arm and leg lifts rather than arm or leg lift alone. Conclusion: The graded lumbar stabilization exercises could be effective ways to strength muscles and increase the patient compliance. According to the physical ability of patients, they will be prescribed the proper level of the exercise intensity, and also only small numbers of exercise were needed to educate, instead of various kinds of different lumbar stabilization exercises.