Trevena, Inc.: Oliceridine

Please refer to your New Drug Application (NDA) dated and received November 2, 2017, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Oliceridine injection, | mg/mL.

We also acknowledge receipt of your amendment dated October 31, 2018, which was not reviewed for this action.

1. You have not submitted adequate data to support the safety of oliceridine for the management of moderate-to-severe acute pain in adult patients for whom an intravenous (IV) opioid is warranted due to concerns related to QT prolongation.

You have not provided adequate data to support that the QT prolonging effects of oliceridine can be mitigated by labeling or monitoring.

The submitted exposure database is not of adequate size to evaluate and support the safety of oliceridine for the proposed labeling.

You have proposed a maximum daily dose of 40 mg ™® You were advised at the End-ofPhase 2 and pre-NDA meetings that the safety database needed to include at least 350 patients exposed to the highest doses for the longest duration of use.

Provide an exposure database that is of adequate size to evaluate and support the safety of oliceridine for the proposed labeling.

Specifically, the safety database must include at least 350 patients exposed to the highest dose proposed for the longest duration of use indicated in the labeling.

Validation reports for the analytical methods used for the leachables study have not been provided to the Agency.

Validate your newly developed analytical methods for leachables as per the ICH Q2 recommendation and provide the validation reports to the Agency.