Voriconazole is a new drug developed to treat fungal infections. As of March 1999, the drug
had been studied in more than 1,900 healthy volunteers or patients with fungal infections.
This study will test extended use of voriconazole in patients with serious fungal infections
for which there are no approved therapies, and in patients who did not improve with or could
not tolerate standard therapy. It will evaluate the drug's safety, effectiveness, and
toleration in these patients.
Patients previous enrolled in protocol 99-C-0094 who improved with voriconazole treatment
are eligible for this study. Before beginning treatment, patients will have a physical
examination, including blood and urine tests, and an eye examination. They may also have
X-ray or CT imaging. Voriconazole will then be given twice a day either by infusion into a
vein or by tablets taken by mouth for up to 12 weeks. Patients will be examined at weeks 4,
8 and 12 of the study and one week after treatment stops. Blood and urine samples will be
collected at each visit. An eye examination will be done at the end of the treatment period
and at other visits if vision problems develop.
Voriconazole is active against fungal infections and may produce fewer side effects than
The objective of this study is to evaluate the efficacy, safety and toleration of
voriconazole in the treatment of systemic or invasive fungal infections due to fungal
pathogens for which there is no licensed therapy or that are unresponsive or intolerant to
treatment with approved systemic antifungal agents. This trial is an extension of the Phase
III multicenter, open label study investigating the utilization of voriconazole for the
treatment of systemic or invasive fungal infections. Enrollment is targeted for 100
patients to be recruited from multiple centers. The patient population will consist of
patients with proven deeply invasive fungal infection for which there is no licensed therapy
or if the patient is failing or intolerant to treatment with approved systemic antifungal
agents and currently on the voriconazole (99-C-0094) protocol. Voriconazole will be
administered intravenously at 3-4 mg/kg q 12 hours or orally at 200-300 mg BID. Efficacy
will be evaluated by clinical, radiological and microbiological response.
Males or (non-pregnant, lactating and nursing) females equal to or greater than 12 years
Previous enrollment into and completion of voriconazole therapy in protocol 99-C-0094
investigating the use of voriconazole in the treatment of invasive fungal disease or
empirical treatment of presumed fungal infections and enrolled within three weeks of
completion of 99-C-0094B.
Clinical benefit was derived from previous voriconazole treatment.
Further clinical benefit is expected with extended voriconazole treatment.
Women of child bearing potential (or less than 2 years post- menopausal) must have a
negative serum pregnancy test at baseline, and must agree to use barrier methods of
contraception during the study.
Signed written informed consent must be obtained at protocol entry.
Assent will be obtained from minors capable of understanding.
Subjects must not have either ongoing serious adverse events probably related to
voriconazole therapy or have ongoing adverse events probably related to voriconazole
therapy which may pose a significant risk on continued therapy.
Must not have previously participated in this trial.
If receiving, must be able to discontinue the following drugs at least 24 hours prior to
randomization: terfenadine, cisapride, and astemizole.
If receiving, must be able to discontinue sulphonylureas at least 24 hours prior to
Must not have received the following drugs within 14 days prior to randomization:
rifampin, carbamazepine, or barbiturates.
Must not have AST, ALT, greater than 10 (upper limit normal).
Must not have serum creatinine greater than 3.0 mg/dl.