Safety and Systemic Exposure of Triamcinolone Acetonide Following Ultrasound-Guided Intra-Articular Injection of Triamcinolone Extended-Release or Standard Triamcinolone Acetonide in Patients with Shoulder Osteoarthritis: An Open-Label, Randomized Study

Abstract

Background and objectives: Osteoarthritis (OA) is a major public health burden. While knee and hip joints are most commonly affected, the glenohumoral (shoulder) joint is also frequently involved. We evaluated the pharmacokinetics and safety/tolerability of triamcinolone acetonide extended-release (TA-ER) and triamcinolone acetonide crystalline suspension (TAcs) in patients with shoulder OA.

Methods: In this phase 2, randomized, open-label, single-dose study (NCT03382262), adults with moderately-to-severely symptomatic shoulder OA for ≥ 6 months randomly received a single ultrasound-guided intra-articular (IA) injection of TA-ER 32 mg or TAcs 40 mg. Safety was evaluated throughout 12 weeks post-injection; blood samples for pharmacokinetic evaluations were collected pre-injection and through Day 85 post-injection.

Results: Among 25 randomized patients, 12 received TA-ER and 13 received TAcs. Most patients were female (60%), and all had moderate (72%) or severe (28%) shoulder OA. Adverse events (AEs) were reported by four (33%) patients following TA-ER and three (23%) following TAcs injection. No AE was serious or led to study discontinuation. Systemic exposure following TAcs was approximately 1.5-fold higher than that following TA-ER injection (geometric mean [GM] AUC0-last 873,543 vs 557,602 h × pg/mL). GM Cmax was also higher in TAcs- than TA-ER-treated patients (2034 vs 1283 pg/mL). Bioequivalence testing confirmed lower systemic TA exposure following TA-ER than TAcs IA injection.

Conclusion: These pharmacokinetic data confirm protracted release of TA from TA-ER following IA injection in patients with shoulder OA. Lower peak and systemic TA exposure following TA-ER suggests TA-ER could potentially confer an improved systemic safety profile over TAcs.

Trial registration number: NCT03382262 (December 22, 2017 retrospectively registered).

Conflict of interest statement

Peter Hanson is an employee of BioSolutions Clinical Research Center; is a paid consultant for Centrexion and Flexion Therapeutics, Inc.; and has received research support from Centrexion, Flexion, and Samumed. Alan Kivitz serves on advisory committees or review panels for AbbVie, Boehringer Ingelheim, Genzyme, Janssen, Pfizer, Regeneron, Sanofi, and UCB; has received compensation for speaking and teaching from Celgene, Flexion Therapeutics, Inc., Genzyme, Horizon, Merck, Novartis, Pfizer, and Sanofi; serves as a paid consultant for Amgen, Gilead, Pfizer, Regeneron, Sanofi, and Sun Pharma Advanced Research; holds stock in Pfizer, Regeneron, and Sanofi; and serves on a steering committee for Flexion. Purvi Mehra is an employee of ARTEMIS Institute for Clinical Research, a clinical research firm with clients in the pharmaceutical and medical device industries. Louis Kwong reports no conflicts of interest. Amy Cinar is an employee of Flexion Therapeutics, Inc. and owns stock/stock options in Flexion. Joelle Lufkin was an independent consultant for Flexion Therapeutics, Inc. at the time the study was conducted and owns stock in Flexion Therapeutics, Inc. Scott D. Kelley was an employee of Flexion Therapeutics, Inc. at the time the study was conducted and owns stock in Flexion Therapeutics, Inc.

© 2021. The Author(s).

Figures

Fig. 1

Disposition of patients with symptomatic shoulder OA receiving single intra-articular injections of TA-ER (32 mg) or TAcs (40 mg). OA osteoarthritis, TAcs triamcinolone acetonide crystalline suspension, TA-ER triamcinolone acetonide extended-release

Fig. 2

Plasma TA concentration-time curves following single intra-articular injections of TA-ER (32 mg) or TAcs (40 mg) to the index joint of adult patients with symptomatic shoulder OA. Data are shown for the first 12 h (A, B) and up to 85 days (C and D) post-injection expressed on linear (A, C) or logarithmic (B, D) scale. CI confidence interval, OA osteoarthritis, TAcs triamcinolone acetonide crystalline suspension, TA-ER triamcinolone acetonide extended-release