Study Description
Immunosuppressed HSCT patients with GVHD need protection25,33
Objective33
To study the efficacy and safety of NOXAFIL® versus fluconazole for the prophylaxis of IFIs in high-risk patients with GVHD following allogeneic hematopoietic stem cell transplantation
Overview33
Patients had similar baseline characteristics33
| Number (%) of Subjects | ||
| NOXAFIL® (n=301) | Fluconazole (n=299) | |
| Primary underlying diagnosis | ||
| Acute myelogenous/non-lymphocytic leukemia | 81 (27) | 66 (22) |
| Acute lymphoblastic leukemia | 25 (8) | 36 (12) |
| Chronic myelogenous leukemia | 98 (33) | 104 (35) |
| Myelodysplastic disorder | 19 (6) | 13 (4) |
| Non-Hodgkin’s lymphoma | 40 (13) | 35 (12) |
| Other* | 42 (14) | 46 (15) |
| None | 0 | 1 (<1) |
| GVHD class at baseline | ||
| Acute grade 1 | 3 (1) | 1 (<1) |
| Acute grade 2 | 135 (45) | 136 (45) |
| Acute grade 3/4 | 64 (21) | 60 (20) |
| Chronic limited | 2 (1) | 1 (<1) |
| Chronic extensive | 96 (32) | 99 (33) |
| Missing | 1 (<1) | 2 (1) |
| Baseline corticosteroids | ||
| High (≥2.0 mg/kg/day) | 41 (14) | 32 (11) |
| Intermediate/Low (<2.0 mg/kg/day but >0 mg/kg/day) | 249 (83) | 256 (86) |
| Dose unknown | 10 (3) | 10 (3) |
| None | 1 (<1) | 1 (<1) |
| No. of immunosuppressive agents at baseline | ||
| 1 | 64 (21) | 48 (16) |
| 2 | 151 (50) | 168 (56) |
| 3 or more | 85 (28) | 82 (27) |
| None | 1 (<1) | 1 (<1) |
* Other includes Hodgkin’s lymphoma, multiple myeloma, aplastic anemia, chronic lymphoblastic leukemia, other leukemias, and all other diagnoses not mentioned above.
Study description25,33
Randomized, multicenter, double-blind and double-dummy, active-control, parallel-group, comparative study
- NOXAFIL® oral suspension 200 mg TID
- Fluconazole 400-mg capsule QD
- Primary efficacy endpoint was proven/probable IFIs at 112 days post-randomization
- Key secondary endpoint was proven/probable IFIs during exposure period (first dose to 7 days after last dose)
Select inclusion criteria33
- HSCT recipients ≥13 years of age
- Grade 2–4 acute GVHD or chronic GVHD
- Treatment with intensive immunosuppressive therapy
- High-dose corticosteroids
- Antithymocyte globulin
- Steroid-sparing regimen including a combination of ≥2 immunosuppressive agents or modalities
Select exclusion criteria33
- History of a proven/probable mould infection or suspected IFI at baseline
- Clinically significant hepatic/renal dysfunction
- Treatment with medications having a potential for adverse interactions with azoles
- Use of other antifungal or investigational agents
- ECG with a prolonged QTc interval by manual reading: QTc >450 msec for men and QTc >470 msec for women
Important Safety Information
NOXAFIL® has been shown to interact with several medications, including drugs that suppress the immune system, and these reactions may be serious. The product label should be consulted when other drugs are prescribed with NOXAFIL®.
Coadministration with sirolimus or ergot alkaloids is contraindicated. Coadministration with the CYP3A4 substrates terfenadine, astemizole, cisapride, pimozide, halofantrine, or quinidine, is also contraindicated since this may result in increased plasma concentrations of these medicinal products, leading to QTc prolongation and rare occurrences of torsades de pointes.
Serious and rare fatal toxicity from cyclosporine has occurred when taken in combination with NOXAFIL® and therefore reduction of the dose of drugs like cyclosporine or tacrolimus and frequent monitoring of drug levels of these medications are necessary when taking them in combination with NOXAFIL®.
In clinical trials, there were infrequent cases of hepatic reactions (eg, mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin, and/or clinical hepatitis). Rarely, more severe hepatic reactions including cholestasis or hepatic failure including fatalities were reported in patients with serious underlying medical conditions (eg, hematologic malignancies) during treatment with posaconazole. Liver function tests should be monitored at the start of and during the course of therapy. Discontinuation of NOXAFIL® must be considered in patients who experience symptoms consistent with liver disease that may be attributable to NOXAFIL®.
The safety and effectiveness of NOXAFIL® in patients below the age of 13 years old have not been established.
The most common treatment-related serious adverse events (1% each) in the combined prophylaxis studies were bilirubinemia, increased hepatic enzymes, hepatocellular damage, nausea, and vomiting.
In the pooled prophylaxis safety analysis, fever, headache, anemia, diarrhea, nausea, vomiting, abdominal pain, hypokalemia, and thrombocytopenia were frequently reported treatment-emergent adverse events.
In clinical studies of OPC and refractory OPC, adverse events were reported more frequently in the pool of patients with refractory OPC. The most commonly reported serious adverse events in refractory OPC patients included fever (13%) and neutropenia (10%).
