Background and aims
Dual Enkephalinase Inhibitors (DENKIs) inhibit the metallopeptidases NEP and APN and increase the bioavailability of enkephalins, which regulate nociception of pain via opioid receptors. STR-324 is a human endogenous compound belonging to the DENKI pharmacological class. This first-in-human study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of STR-324 in healthy male subjects.

Methods
This study was a placebo-controlled partial cross-over study following an interleaving dosing schedule in 30 subjects in two groups, each receiving four dose levels (0.00425–11.475mg/h) of STR-324 or placebo (ratio 4:1) by 4-hour intravenous infusion over four treatment periods (part 1). In part 2, 48 subjects divided in three groups received either the active drug or placebo (ratio 3:1) by 48-hour intravenous infusion. The three dose levels (1.25–11.25mg/h) were selected based on tolerability in part 1 and on expected analgesic activity.
Treatment-emergent (serious) adverse events (TE(S)AEs), pharmacokinetics and effects on neurocognitive tasks and on a nociceptive test battery were evaluated.

Results
No specific pattern of AE was identified. No clinically relevant changes in ECG, vital signs or laboratory tests were observed. Analyses of the analgesic effects and the pharmacokinetic profile of STR-324 are ongoing. 

Conclusions
STR-324 displayed favourable safety and tolerability profiles in healthy subjects at all doses up to 11.475mg/h. Final results on pharmacokinetic and pharmacodynamic endpoints will be presented at the conference. 

Disclosure
This study was supported by Stragen France SAS.

A FIRST-IN-HUMAN CLINICAL TRIAL TO ASSESS SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF STR-324, A DUAL ENKELPHALINASE INHIBITOR AND THERAPEUTIC CANDIDATE FOR PAIN MANAGEMENT