An open-label, multicenter, randomized, parallel, single-dose, comparative bioavailability study of two triamcinolone hexacetonide injectable suspensions in patients with knee osteoarthritis

Abstract

Background: Triamcinolone hexacetonide (THA), a synthetic glucocorticoid with low solubility, can provide sustained pain relief and less systemic side effects in patients with knee osteoarthritis. This study aimed to characterize pharmacokinetic profile of THA-test product containing 20 mg/ml injectable suspension and compare its bioavailability with the standard reference in Indian patients with knee osteoarthritis. Methods: In this open-label, randomized, multicenter study, 44 adult patients were randomized (1:1; test n=23, reference n=21) to receive a single dose of test or reference products. The primary objective was to characterize the pharmacokinetic profile and compare bioavailability of both products via serum triamcinolone acetonide (TCA) concentration. Secondary objectives included safety and tolerability evaluation, impact on hypothalamic-pituitary-adrenal axis, and efficacy of test and reference products in reducing index knee pain. Results: Both products were absorbed with a median Tmax of 23.9 hours. Comparative bioavailability analysis demonstrated no statistically significant formulation effect for ln-transformed Cmax (1098.052 pg/ml for test, 1333.850 pg/ml for reference) and AUC0-t (159112.561 pg×h/ml for test, 211531.035 pg×h/ml for reference) for TCA. T/R ratio for Cmax was 82.3% and T/R ratio for AUC0-t was 75.2%, with >100% inter-subject variability for both Cmax and AUC0-t. Additionally, recovery time of cortisol levels of test and reference arms was 96 hours and 456 hours, respectively. Both products significantly reduced knee pain (p<0.0001). Conclusions: The test product provided lower systemic exposure and faster recovery of serum cortisol levels than the reference, while still providing similar beneficial effect in sustained index knee pain reduction.