ystemic antifungal therapy (Patients might have met more than one of these criteria). This study assessed patients while on treatment plus 7 days and 100 days postrandomization. The mean duration of therapy was comparable between the 2 treatment groups (29 days, posaconazole; 25 days, fluconazole or itraconazole). Table 18 contains the results from Oral Suspension Study 2.
Table 18: Results from Open-Label Clinical Study 2 in Prophylaxis of IFI in All Randomized Patients with Hematologic Malignancy and Prolonged Neutropenia: Oral Suspension Study 2
Posaconazole
n=304
Fluconazole/Itraconazole
n=298
* 95% confidence interval (posaconazole-fluconazole/itraconazole) = (-22.9%, -7.8%).† Patients may have met more than one criterion defining failure.‡ Use of systemic antifungal therapy (SAF) criterion is based on protocol definitions (empiric/IFI usage >3 consecutive days).§ Patients who are lost to follow-up (not observed for 100 days), and who did not meet another clinical failure endpoint. These patients were considered failures.
On therapy plus 7 days
Clinical Failure*,† 82 (27%) 126 (42%)
Failure due to:
Proven/Probable IFI 7 (2%) 25 (8%)
(Aspergillus) 2 (1%) 20 (7%)
(Candida) 3 (1%) 2 (1%)
(Other) 2 (1%) 3 (1%)
All Deaths 17 (6%) 25 (8%)
Proven/probable fungal infection prior to death 1 (<1%) 2 (1%)
SAF‡ 67 (22%) 98 (33%)
Through 100 days postrandomization
Clinical Failure† 158 (52%) 191 (64%)
Failure due to:
Proven/Probable IFI 14 (5%) 33 (11%)
(Aspergillus) 2 (1%) 26 (9%)
(Candida) 10 (3%) 4 (1%)
(Other) 2 (1%) 3 (1%)
All Deaths 44 (14%) 64 (21%)
Proven/probable fungal infection prior to death 2 (1%) 16 (5%)
SAF‡ 98 (32%) 125 (42%)
Event free lost to follow-up§ 34 (11%) 24 (8%)
In summary, 2 clinical studies of prophylaxis were conducted with the posaconazole oral suspension. As seen in the accompanying tables (Tables 17 and 18), clinical failure represented a composite endpoint of breakthrough IFI, mortality and use of systemic antifungal therapy. In Oral Suspension Study 1 (Table 17), the clinical failure rate of posaconazole (33%) was similar to fluconazole (37%), (95% CI for the difference posaconazole–comparator -11.5% to 3.7%) while in Oral Suspension Study 2 (Table 18) clinical failure was lower for patients treated with posaconazole (27%) when compared to patients treated with fluconazole or itraconazole (42%), (95% CI for the difference posaconazole–comparator -22.9% to -7.8%).
All-cause mortality was similar at 16 weeks for both treatment arms in Oral Suspension Study 1 [POS 58/301 (19%) vs. FLU 59/299 (20%)]; all-cause mortality was lower at 100 days for posaconazole-treated patients in Oral Suspension Study 2 [POS 44/304 (14%) vs. FLU/ITZ 64/298 (21%)]. Both studies demonstrated substantially fewer breakthrough infections caused by Aspergillus species in patients receiving posaconazole prophylaxis when compared to patients receiving fluconazole or itraconazole.
14.2 Treatment of Oropharyngeal Candidiasis with Posaconazole Oral Suspension
Posaconazole Oral Suspension Study 3 was a randomized, controlled, eva luator-blinded study in HIV-infected patients with oropharyngeal candidiasis. Patients were treated with posaconazole or f
