Why carry out this study?

Oliceridine, a new intravenous opioid, is shown in nonclinical studies to be a G protein-biased agonist at the μ-opioid receptor. This preferential activity may result in potent analgesia with reduced recruitment of β-arrestin, a signaling pathway associated with opioid-related adverse events (ORAEs).

In two randomized, placebo- and active-controlled phase 3 studies, we have previously reported that oliceridine administered via patient-controlled analgesia provided effective analgesia with a favorable safety profile.

An understanding of the relationship between efficacy and safety is important to assess the benefit–risk profile of a new compound. Randomized clinical trials are typically designed to evaluate efficacy and the statistical analytical methods used may be underpowered to identify any differences on the adverse event profile between treatments.

Logistic regression offers a framework that allows an estimate of the probability of an adverse reaction associated with a treatment, including the assessment of the strength of association. It is routinely used in the evaluation of post-marketing adverse effects reports to determine association of causality.

In this exploratory analysis, we utilized the logistic regression method to evaluate the safety of oliceridine when adjusted for equal levels of analgesia compared to morphine using data from the two pivotal randomized clinical trials. The ORAEs of nausea, vomiting, sedation, dizziness, pruritus, and hypoxia, with at least one treatment-emergent adverse event, was used as the composite safety endpoint.

What was learned from the study?

The analysis demonstrates that at comparable levels of analgesia, patients receiving oliceridine were less likely to experience the composite safety endpoint consisting of ORAEs compared to patients treated with morphine.