A phase 3 study has found that oliceridine was generally well tolerated in a real-world population of patients with moderate to severe acute pain for whom a parenteral opioid was warranted, according to a study presented here at the 2018 Annual Meeting of the American Society of Anesthesiologists (ASA).
“I was happy to see that oliceridine was useful as an analgesic agent and provided rapid pain relief and the pain control was sustained,” said lead author Harold Minkowitz, MD, Memorial Hermann Memorial City Medical Center, Houston, Texas. “In the diverse population studied, it provided titratable control of moderate to severe acute pain.”
The use of opioids to treat pain has surged in recent years, but managing pain with conventional opioids can be challenging due to dose-limiting adverse events that can compromise pain outcomes. These opioid-related adverse events may be particularly problematic in patients of advanced age, those who are receiving polypharmacy, and those with comorbidities.
Researchers have found that some opioid-related adverse events, including gastrointestinal and respiratory complications, may be associated with the unselective activation of G-protein and beta-arrestin signalling pathways by conventional opioids.
The investigational analgesic oliceridine is a G protein-biased ligand at the µ-opioid receptor, which acts as a full agonist for G-protein coupling but exhibits limited beta-arrestin recruitment.
In phase 3 controlled studies, oliceridine has been shown to be an effective analgesia with the potential for improved safety and tolerability compared with morphine in patients who have undergone bunionectomy and abdominoplasty.
In the current phase 3 open-label study, Dr. Minkowitz and colleagues evaluated the safety/tolerability and efficacy of oliceridine in moderate to severe acute pain for which parenteral opioid therapy was warranted in patients undergoing representative surgeries and procedures.
Study sites included ambulatory surgical centres and hospital-based outpatient, inpatient, and emergency departments. They treated 768 adult patients with a score ≥4 on an 11-point numeric rating scale for pain intensity with intravenous oliceridine as needed (duration ≤14 days) via clinician-administered IV bolus dosing (1-3 mg) and/or patient-controlled analgesia ( (loading dose of 1.5 mg; demand dose of 0.5 mg; 6-minute lockout interval).
The majority of the patients were female (65%) and white (78%) with a mean age of 54.1 years. Mean baseline pain score was 6.3. All patients had at least 1 comorbid condition, most (78%) were overweight/obese, and most received multimodal pain treatment.
They saw a mean reduction from baseline in pain score of 2.2 at 30 minutes after the first dose, and this reduction was maintained until the end of treatment.
Adverse events occurred in 64% of the patients and were mostly of mild (37%) or moderate (25%) severity. The incidence of significant adverse events and adverse events leading to early discontinuation was low (3% and 2%, respectively), and there were no deaths.
The incidence of adverse events was lowest in patients receiving ≤4 mg, and it increased and generally plateaued in those receiving higher doses. The most common adverse events were nausea (31%), constipation (11%), and vomiting (10%). There were no treatment-related respiratory arrests or critical events, and they reported no unexpected findings for vital signs, oxygen saturation, somnolence, or sedation.
“We now have the potential for a new treatment option in our armamentarium to treat moderate to severe pain in a controlled acute care setting,” said Dr. Minkowitz. “The study demonstrated safety in a wide variety of procedures and patients with a vast array of comorbidities.”