* 33 patients contributed to the analyses of these parameters 

† 14 patients contributed to the analyses of these parameters 

1 Median (min, max) values for t max 

Triamcinolone Acetonide 

PK Parameters1 ZILRETTA 

(N=60) Triamcinolone Acetonide 

(N=18) 

Cmax (pg/mL) 1143.7 

(611.06)  21062.2 

(18466.79)  

AUC0-24 hour 

(pg•h/mL) 21219.2 

(11325.62)  297545.3 

(222402.77)  

AUC0-inf 

(pg•h/mL) 842149.2 

(1062004.97)*  1567565.0 

(1246330.95) † 

tmax 

(h) 7 

(1, 1008)  6 

(2, 24)  

t1/2 

(h) 633.9 

(893.0)*  146.9 

(213.29) †  

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 

Carcinogenesis 

Long-term animal studies to eva luate the carcinogenic potential of ZILRETTA have not been conducted. 

Mutagenesis 

Adequate mutagenicity studies have not been conducted with ZILRETTA. 

Impairment of Fertility 

Studies in animals to eva luate the impairment of fertility of ZILRETTA have not been conducted. 

14 CLINICAL STUDIES

The efficacy of ZILRETTA was demonstrated in a multi-center, international, randomized, double-blind, parallel-arm, placebo- and active-controlled study in patients with osteoarthritis pain of the knee. A total of 484 patients (ZILRETTA 32 mg, N=161; placebo [saline], N=162; active control [a crystalline suspension, immediate-release formulation of triamcinolone acetonide 40 mg], N=161) were treated and followed for up to 24 weeks. Patients had a mean age of 62 (range 40 to 85 years); baseline demographics and disease characteristics were balanced across treatment arms. Twenty-five percent (25%) of patients had received at least one prior corticosteroid intra-articular injection more than 3 months prior to treatment. A total of 470 patients (97%) completed follow-up to Week 12, the time point for primary efficacy determination, and 443 (91.5%) completed to Week 24. 

The primary efficacy endpoint comparing ZILRETTA to placebo was change from baseline at Week 12 in the weekly mean of the Average Daily Pain intensity scores (ADP) as assessed by a 0-10 Numeric Rating Scale (NRS). ZILRETTA demonstrated a statistically significant reduction in pain intensity at the primary endpoint vs placebo. ZILRETTA also demonstrated a reduction in pain intensity scores each week from Weeks 1 through 12 ( Figure 1). 

In a secondary exploratory analysis, statistical significance was not demonstrated between the ZILRETTA and the active control (immediate-release triamcinolone acetonide) treatment groups for the change from baseline at Week 12 in weekly mean ADP. 

Figure 1: Weekly Change from Baseline to Week 12 in Average Daily Pain 

Figure 1  

16 HOW SUPPLIED/STORAGE AND HANDLING

Description NDC Presentation/How Supplied 

ZILRETTA  NDC 70801-003-01  ZILRETTA (triamcinolone acetonide extended-release injectable suspension) single-dose kit.