Adverse Reactions Following First-Dose Administration of Co-Crystal of Tramadol-Celecoxib Versus Tramadol Alone for Moderate-To-Severe Acute Pain.

INTRODUCTION

Phase 3 clinical trials in moderate-to-severe acute pain have shown that co-crystal of tramadol-celecoxib (CTC) has improved efficacy and comparable tolerability versus immediate-release tramadol 50 mg alone, with a similar tramadol daily dose, over a 48-h treatment period. However, it is not known how first-dose tolerability compares, given that the administered dose of tramadol is higher in CTC 200 mg (88 mg) versus immediate-release tramadol 50 mg. This was explored in a post hoc analysis of a pivotal phase 3 trial.

METHODS

A randomized, double-blind, factorial, active- and placebo-controlled phase 3 trial was conducted in patients with moderate-to-severe acute postoperative pain (NCT03108482) and has been previously reported. This post hoc analysis evaluated the prevalence of the four most common study drug-related, opioid-associated, treatment-emergent adverse reactions reported in phase 3 CTC clinical trials: somnolence, nausea, dizziness, and vomiting. Prevalence was evaluated in 2-h intervals, up to 6 h post first dose (just before second-dose administration) of CTC 200 mg or immediate-release tramadol 50 mg p.o. Descriptive analysis was performed.

RESULTS

Each group comprised 183 participants for analysis. The proportions of patients reporting drug-related, treatment-emergent adverse reactions of somnolence, nausea, dizziness, and vomiting were similar between treatment groups at 2, 4, and 6 h following the first dose.

CONCLUSIONS

This post hoc analysis indicates that the higher dose of tramadol (88 mg) given in CTC 200 mg did not result in an increase in drug-related adverse reactions after first-dose administration, and had a similar tolerability profile, compared with immediate-release tramadol 50 mg alone (the lowest dose recommended for the management of moderate-to-severe acute pain). This is in line with earlier findings for the 48-h treatment period of this phase 3 trial and may be explained by CTC's differentiated physiochemical properties related to its co-crystal structure. These findings may have utility for practicing clinicians.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03108482.