(7%)
(Candida) 4 (1%) 4 (1%)
(Other) 5 (2%) 2 (1%)
All Deaths 58 (19%) 59 (20%)
Proven/probable fungal infection prior to death 10 (3%) 16 (5%)
SAF† 26 (9%) 30 (10%)
Event free lost to follow-up§ 24 (8%) 30 (10%)
The second study (Oral Suspension Study 2) was a randomized, open-label study that compared posaconazole oral suspension (200 mg 3 times a day) with fluconazole suspension (400 mg once daily) or itraconazole oral solution (200 mg twice a day) as prophylaxis against IFIs in neutropenic patients who were receiving cytotoxic chemotherapy for AML or MDS. As in Oral Suspension Study 1, efficacy of prophylaxis was eva luated using a composite endpoint of proven/probable IFIs, death, or treatment with systemic 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 we
