Initiation of PF614 Phase 3 Trial: A New Chapter in Opioid Safety

Ensysce Biosciences has initiated a phase 3 trial of PF614, a next-generation opioid with an intrinsic abuse-deterrent layer designed to limit rapid-onset exposure while treating moderate–severe postoperative pain.

The randomized, double‑blind study is enrolling adult abdominoplasty patients with moderate–severe postoperative pain in a multicenter, placebo-controlled surgical model. The protocol uses objective analgesic measures and opioid-consumption endpoints to evaluate both pain relief and opioid‑sparing potential, supporting generalizability through its surgical comparator arms.

PF614’s design incorporates an intrinsic chemical layer intended to blunt rapid concentration spikes that can drive misuse, producing a smoother plasma profile rather than a physical tamper-resistant barrier or the incorporation of opioid receptor antagonists. This pharmacokinetic strategy aims to reduce the theoretical likelihood of rapid-onset misuse by lowering bolus-like exposure, without implying clinical proof that abuse will be reduced.

Primary and key secondary endpoints include validated pain-intensity measures (time‑weighted average or AUC pain scores) and cumulative opioid consumption to quantify opioid‑sparing effects. Responder rates and duration of analgesia will serve as clinically meaningful efficacy readouts; safety monitoring will capture treatment‑emergent adverse events and opioid‑related respiratory depression during the immediate postoperative window typical for abdominoplasty studies.