Comparison of posaconazole adverse event profiles in healthy volunteers and in patients with invasive fungal infections

Abstract number: 1134_02_305

Pedicone L., Ullmann A., Graybill J., Sansone A., Courtney R., Laughlin M., Raad I.

Objectives:

To better define the adverse event (AE) profile of posaconazole (POS), we compared the safety profiles of patients with invasive fungal infections (IFIs) enrolled in POS clinical trials with those of healthy volunteers enrolled in clinical pharmacology studies.

Methods:

AE analyses from 428 patients with IFIs from 2 open-label clinical trials and from 449 healthy volunteers from 18 clinical pharmacology trials were compared. In the healthy volunteer studies, compliance with dosing regimens was strictly enforced and participants had no significant underlying diseases or concomitant medications that could confound interpretation of safety data. Therefore, for the purpose of this analysis, the healthy volunteers served as a control group for the patient population. In both groups, most subjects received POS 800 mg/d in divided doses.

Results:

Treatment-related AEs (TRAEs) occurred in 44% (196/449) of healthy volunteers; the most common were headache (17%), dry mouth (9%), and dizziness (6%). In patients, many AEs were consistent with underlying diseases. TRAEs occurred in 38% of patients (164/428); the most common were nausea (8%), vomiting (6%), headache (5%), abdominal pain (4%), and diarrhoea (4%). Notably, gastrointestinal (GI) TRAEs occurred in 18% of healthy volunteers and 19% of patients. Treatment-related abnormal liver function test results were observed in 2% of healthy volunteers and up to 3% of patients. There were no clinically significant differences in mean QTc interval change from baseline in either population. Serious AEs (SAE) considered possibly or probably related to POS occurred in 35 (8%) patients and 1 healthy volunteer. The most common SAEs in patients were altered drug level, increased hepatic enzymes, nausea, rash, and vomiting (1% each). No significant trends related to age, sex, or race were observed in either group. Additionally, no unique TRAEs were identified in patients during long-term exposure (>6 months) compared with those identified during shorter-duration therapy.

Conclusion:

The safety profile of POS in patients was similar to that observed in a controlled population of healthy volunteers and is likely indicative of what will be observed in the clinical setting. Headache and GI events (nausea, vomiting, abdominal pain, diarrhoea) were the most common TRAEs observed in patients. Given its favorable safety profile, POS should provide an additional treatment option for severely ill patients with IFIs.