Safety of Injectable HPβCD-Diclofenac in Older Patients with Acute Moderate-to-Severe Postoperative Pain: A Pooled Analysis of Three Phase III Trials

BACKGROUND: Hydroxypropyl-β-cyclodextrin-diclofenac (HPβCD-diclofenac) is an NSAID used to treat acute moderate-to-severe postoperative pain. This post hoc analysis investigated the safety of HPβCD-diclofenac in patients aged ≥ 65 years. METHODS: Data from three phase III trials of HPβCD-diclofenac in adult patients with acute moderate-to-severe postoperative pain were pooled (NCT00448110, NCT00507026, and NCT00726388). Patients who received one or more dose of HPβCD-diclofenac or placebo were included and stratified according to age: < 65, 65–74, or ≥ 75 years. Numerical and categorical variables were compared across the groups using ANOVA and Cochran–Mantel–Haenszel tests, respectively. Cochran–Mantel–Haenszel relative risks compared with placebo were calculated, adjusted by study. RESULTS: Overall, 1289 patients were included: 878, 282, and 129 in the < 65, 65–74, and ≥ 75-years groups, respectively. Overall incidence of treatment-emergent adverse events (TEAEs) was similar in the three groups (p = 0.4360). Incidences of postoperative anemia (p < 0.0001), constipation (p = 0.0017), and hypotension (p = 0.0003) increased significantly across the age groups, whereas headache (p = 0.0008) and flatulence (p = 0.0118) decreased significantly. Relative risks for all System Organ Class categories and preferred terms investigated were similar among the groups and similar to placebo. CONCLUSIONS: Overall incidence of TEAEs in patients aged 65–74 or ≥ 75 years was similar to patients aged < 65 years. The groups displayed similar relative risks for the most frequent TEAEs, which were all similar to placebo. The TEAE profiles of the groups showed differences, all of which may be anticipated due to age-related differences in susceptibility and the types of surgery most commonly performed in each group. CLINICALTRIALS.GOV IDENTIFIERS: NCT00448110, NCT00507026, and NCT00726388.