Phase I Pilot Study of a Novel Celecoxib-Containing Paste for Local Application Following Mandibular Third Molar...

Postoperative pain after mandibular third molar extraction remains a significant clinical challenge. Local drug delivery to the extraction socket may enable targeted analgesia with minimal systemic exposure. This first-in-human pilot study aimed to evaluate the safety and tolerability of a novel celecoxib-containing paste applied to extraction sockets and to assess the feasibility of the dose-escalation design, outcome measures, and study procedures to inform a future definitive randomized controlled trial.

This single-center, open-label, dose-escalation study enrolled 18 adult patients undergoing mandibular third molar extraction in three sequential cohorts (n = 6 each): low (0.5 mg/mL), medium (1.0 mg/mL), and high (2.0 mg/mL) celecoxib paste. Following extraction, 1-2 mL of paste was applied to the socket. The primary safety outcome was the incidence of alveolar osteitis (dry socket) by day 8. Feasibility outcomes included recruitment and retention rates, protocol adherence, and the performance of exploratory efficacy measures, including the visual analog scale (VAS) pain scores, rescue analgesic consumption, and patient-reported effectiveness. The study followed the Consolidated Standards of Reporting Trials (CONSORT) extension for pilot and feasibility trials, adapted for a non-randomized design.

All 18 participants completed the study with no withdrawals (retention rate: 100%). No cases of dry socket or treatment-related adverse events were observed (0/18; 95% CI: 0-15.3%). Mean VAS pain scores declined consistently across all cohorts from days 1 to 5. Higher-dose groups showed numerically greater reductions in rescue analgesic consumption. The dose-escalation protocol, outcome measures, and data collection procedures were feasible and performed as intended.

Application of celecoxib-containing paste to extraction sockets was well tolerated without dry socket or other safety concerns. The study procedures were feasible, and preliminary efficacy signals support progression to a larger, randomized, placebo-controlled trial.

Japan Registry of Clinical Trials (jRCT; https://jrct.niph.go.jp/; identifier: jRCT2051230162). Registered on January 11, 2024.