7 years, and the mean number of menopausal years was 15.7. In the subgroup

of patients with inflammatory biomarker data (n = 96, placebo 33 patients, acetaminophen 33 patients, fluvastatin 30 patients), demographic and background characteristics were similar to those in the ITT population, and the treatment groups remained well matched. Compliance was excellent and well balanced across treatment groups. There were no compliance issues with respect to fluvastatin, as the sole dose was administered by study personnel; for acetaminophen and acetaminophen-matching placebo, the mean number of capsules taken ranged from 21.2 to 21.5 (out of 24). Efficacy outcomes Following a single infusion of ZOL 5 mg, acetaminophen was found to be superior to placebo in preventing or reducing post-dose symptoms over the subsequent 3-day period. Clinically significant increases in oral

body temperature or SBI-0206965 mouse use of rescue medication occurred in 60.7% (162) of 267 patients in the placebo group vs. 39.8% (105 of 264 patients) in the acetaminophen group (p < 0.001; Fig. 1). In contrast, no effect was observed from a single dose of fluvastatin taken 45 min prior to the ZOL infusion, with a total of 61.8% of patients (162 of 262) having increased temperature or using rescue medication. Subgroup analyses showed that all age groups (45–55 years, 56–64 years, and 65 years and older) experienced significant benefits from LY411575 price acetaminophen. Fig. 1 Proportion of patients with fever (clinically significant increase in oral body temperature [1°C or more from baseline and 38.5°C or more overall]) or use of at least one dose of rescue medication during the 3-day period following IV zoledronic acid infusion (intent-to-treat

population). Cross-hatching indicates proportion of patients in each group with one or more episodes of fever LDN-193189 mouse recorded in the patient diary (no p values shown for the latter comparisons). acet acetaminophen, fluv fluvastatin, plac placebo Acetaminophen also produced significant benefits with respect to secondary efficacy variables. Compared with placebo, acetaminophen Tideglusib significantly decreased the proportion of patients with increased body temperature, of those who used rescue medication, of those who experienced a major increase in severity of symptoms, and of those who reported at least one episode of severe symptoms. Fluvastatin did not significantly affect any symptom variables (Table 1). Table 1 Clinically significant increase in oral body temperature, rescue medication use, worsening symptoms, and severe symptoms during the 3-day period following IV zoledronic acid infusion Variables PLAC (N = 267) ACET (N = 264) FLUV (N = 262) Number Percentage (%) Number Percentage (%) Number Percentage (%) Clinically significant increase in temperaturea 28 10.5 13 4.9b 30 11.5 Use of rescue medication 153 57.3 102 38.6c 156 59.5 Major increase in severity of symptoms Feeling feverish 105 39.3 62 23.5c 104 39.7 Headache 104 39.0 67 25.4c 115 43.