Results from respiratory physiology study of head-to-head comparison of Olinvyk and IV morphine in elderly/overweight subjects.

Dr. Dahan’s team compared the analgesic and respiratory effects of two doses of Olinvyk (0.5mg and 2.0mg) and morphine (2.0mg and 8.0mg) administered intravenously in a population of elderly individuals (age range 56 to 87 years, mean age = 71.2) across a range of body weight (BMI range from 20 to 34 kg/m2, mean BMI= 26.3). Subjects were tested on 4 occasions and randomized by drug and dose. On each visit, the ventilatory response to inhaled carbon dioxide was measured to evaluate the potential effect of the drug on the brain respiratory centers. Elderly and overweight patients are known to be at higher risk of respiratory depression with the use of opioid medications. This study hypothesized that, at similar levels of analgesia, there would be a reduced impact on respiratory function with Olinvyk compared to IV morphine. The primary endpoint of the study was ventilatory rate at an extrapolated PCO2 of 55 mmHg (VE55).

Key Findings : i. Both Olinvyk and IV morphine achieved comparable levels of pain relief. However, a statistically significantly reduced impact on respiratory function was observed in patients treated with Olinvyk compared to IV morphine, as measured by the mean respiratory ventilation profiles over time (P < 0.0001). ii. In contrast to the lower dose of IV morphine, very little impact on respiratory function was observed with the lower dose of Olinvyk. iii. At the higher dose of both drugs studied, less respiratory depression over the 6 h measurement period was observed with Olinvyk. The peak level was lower for Olinvyk compared to morphine, though this difference was not statistically significant (P > 0.05). In addition, in contrast to morphine, respiratory function at the higher dose of Olinvyk rapidly returned toward baseline from 3 hours onward (all time points P < 0.05 in pairwise comparison). iv. The data replicate the results from a previously reported study in younger subjects. v. Comparing the sensitivity of the impact on respiratory function from the earlier study and the results from the current study suggests that there is a nearly identical impact on respiratory function with Olinvyk in the younger and elderly age groups, while IV morphine data suggests an increase in impact in the elderly compared to the younger subjects.

“We believe these data from Dr. Dahan’s study team are important. They replicate the results from an earlier study reported by Trevena in younger subjects using a similar methodology, and they extend our knowledge to patients who are at higher risk for the development of respiratory depression with the use of opioids, namely elderly and overweight patients,” said Mark A. Demitrack, M.D., Senior Vice President and Chief Medical Officer of Trevena. “As with all opioids, serious, life-threatening, or fatal respiratory depression may occur in patients treated with Olinvyk. We look forward to seeing further analysis of this data by Dr. Dahan’s team and working with him to see these results reported to the wider scientific community and submitted for publication in the near future.”