Intervention: Itraconazole
Trial phase: Phase 2 | Phase 3
ATC code: J02AC02
SMILES: CCC(C)n1ncn(-c2ccc(N3CCN(c4ccc(OCC5COC(Cn6cncn6)(c6ccc(Cl)cc6Cl)O5)cc4)CC3)cc2)c1=O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 46
Group description: Stage 1: Day 1-3 two 100 mg capsules three times daily with food. Days 4-42 two 100 mg capsules twice daily with food.

Stage 2 : Days 43-180 two 100 mg capsules twice daily with food

Conventional itraconazole: Conventional itraconazole comparator drug will consist of two 100 mg capsules to be taken three times a day with food for days 1-3 of study. For days 4-180 of study, two 100 mg capsules will be taken twice daily with food.
Eligibility criteria:
Inclusion Criteria:

Male and female patients age > 18 years who have given written informed consent to participate

Patients with a proven or probable endemic mycosis (Histoplasma, Coccidioides, Paracoccidioides, Blastomyces, Sporothrix, Talaromyces marneffei (formerly Penicillium marneffei) according to current EORTC/MSG (Mycoses Study Group) criteria, including patients who:

Are immunosuppressed, including as a result of HIV/AIDS
Have had a heart, lung or bone marrow transplant
Have had chemotherapy for cancer
Are otherwise normal hosts

Exclusion Criteria:

Significant liver dysfunction as evidenced by at least 5 times greater than upper limits of normal baseline ALT (alanine aminotransferase) , AST (aspartate aminotransferase), alkaline phosphatase, or total bilirubin.
Use of an alternative antifungal therapy (IV or oral) for more than 14 days for this infection, with the exception of Coccidioidomycosis. Subjects with Coccidioidomycosis who previously received fluconazole therapy for more than 14 days may be included, if in the opinion of the investigator, they are having an inadequate response or, are intolerant of fluconazole (e.g. due to adverse events). Such subjects must washout from fluconazole for 7 days (~5 half-lives of fluconazole) before starting investigational therapy.
Evidence of CNS (central nervous system) infection.
Unable to take PO medications.

Female patients who are lactating or pregnant.

Women should be:

Postmenopausal for 1 year,
Post-hysterectomy or bilateral oophorectomy,
If of child bearing potential have a negative β-HCG (human chorionic gonadotropin) at screening and using highly effective method of birth control throughout course of study or remain abstinent for duration of study.
Documented intolerance, allergy or hypersensitivity to an azole.
Inability to comply with study treatment, study visits, and study procedures.
Known history of congestive cardiac failure on medical treatment, fungal endocarditis, or other causes of ventricular dysfunction that may outweigh the benefit of itraconazole.
Patients with active TB (tuberculosis)
Concurrent use of astemizole, rifampin/rifampicin, rifabutin, ergot alkaloids, long acting barbiturates, carbamazepine, pimozide, quinidine, neostigmine, terfenadine, ketoconazole, valproic acid, or St. John's wort in the 5 days prior to first administration of study drug.
Any known or suspected condition of the patient that may jeopardize adherence to the protocol requirements or impede the accurate measurement of efficacy.
Treatment with any investigational agent in the 30 days prior to study entry.
Patients unlikely to survive 30 days (including severe fungal disease defined by systolic blood pressure (SBP) < 90; hypoxia < 60).
Patients with body weight < 40 kg.