A Randomized, Open-Label, Single-Dose Study to Assess Safety and Systemic Exposure of Triamcinolone Acetonide Extended-Release in Patients With Hip Osteoarthritis

Abstract

Introduction: Intra-articular (IA) corticosteroids, including triamcinolone acetonide (TA), are a recommended treatment for hip osteoarthritis. We compared the safety and systemic exposure of TA extended-release (TA-ER) versus TA crystalline suspension (TAcs) in patients with hip osteoarthritis.

Methods: In this phase 2, randomized, multicenter, open-label, single-dose study (NCT03382262), patients with hip osteoarthritis were randomly assigned 1:1 to receive single IA injections of TA-ER 32 mg or TAcs 40 mg. Safety assessments included treatment-emergent adverse events (TEAEs). Blood samples were collected for pharmacokinetic (PK) analysis up to day 85. PK parameters included area under the concentration-time curve, total body drug clearance, maximum concentration (Cmax), mean residence time, half-life, and time to maximum concentration.

Results: Of 30 patients (TA-ER: n = 15; TAcs: n = 15) randomized and included in the Safety Population, 25 patients were evaluated in the PK Population. TEAEs were reported in four of 15 (26.7%) patients who received TA-ER and in seven of 15 (46.7%) patients who received TAcs. The most common TEAEs included arthralgia and headache. All TEAEs were of grade 1 or 2 in severity. TA-ER produced substantially lower peak plasma TA concentrations compared with TAcs (Cmax geometric mean: 890.4 vs. 5549.4 pg/ml), and these were less variable with TA-ER versus TAcs. Similarly, overall TA systemic exposure was substantially lower for TA-ER versus TAcs, with gradual elimination from systemic circulation through day 85.

Conclusions: Following a single IA injection in the hip, TA-ER was generally well tolerated, with a safety profile comparable to that of TAcs. Systemic TA exposure was markedly lower in TA-ER-treated patients, consistent with the PK profile observed in knee osteoarthritis.

Clinicaltrials: gov identifier: NCT03382262.

Keywords: Corticosteroids; Hip osteoarthritis; Pharmacokinetics; Triamcinolone acetonide crystalline suspension; Triamcinolone acetonide extended-release.

© 2022. The Author(s).

Figures

Fig. 1

Patient disposition. PK pharmacokinetic, TAcs triamcinolone acetonide crystalline suspension, TA-ER triamcinolone acetonide extended-release. aOne patient was enrolled in the study at two different study centers and received TAcs at one study center and then received TA-ER 5 days later at another study center, with both study drugs administered in the right hip; this patient is included in both treatment groups. bThe Safety Population included all patients who received any amount of study treatment. The patient noted above who received two injections is included in both treatment groups. cThe PK Population included all patients from the Safety Population who received a full dose of study drug (three patients excluded from TA-ER PK Population because of incomplete dosing), completed PK sampling, and had sufficient plasma concentration measurements for PK analysis. The patient noted above who received two injections (TAcs followed by TA-ER) is excluded from both treatment groups

Fig. 2

Plasma TA concentration over time after injection of TA-ER (n = 11) or TAcs (n = 14). a Log-linear GM (95% CI) baseline to day 85; b Linear–linear GM (95% CI) baseline to day 85; c Log-linear GM (95% CI) baseline to hour 24; d Linear–linear GM (95% CI) baseline to hour 24 (PK Population). CI confidence interval, GM geometric mean, PK pharmacokinetic, TA triamcinolone acetonide, TAcs triamcinolone acetonide crystalline suspension, TA-ER triamcinolone acetonide extended-release