View clinical trials related to Invasive Aspergillosis.
Filter by:Open label radiolabelled metabolism study of intravenous and oral solution forms of F901318. Five healthy male subjects will receive IV and five will receive an oral solution. Blood, urine and faeces will be collected over a period adequate to obtain 90% recovery of parent compound and to determine the metabolic profile of both IV and oral forms.
Patients with acute myeloid leukemia (AML) are at risk to develop severe infections whose invasive aspergillosis (IA). These infections are leading to an important morbidity and mortality. Antifungal prophylaxis is recommended by posaconazole for AML patients during neutropenia induced by induction chemotherapy. Their application is not uniform.
Single dose comparison of liquid and solid formulation, followed by study of effect of high fat breakfast. Evaluation of multiple dose pharmacokinetics and tolerability
The incidence of invasive pulmonary aspergillosis (IPA) is increasing in all parts of the world. Despite introduction of new antifungal agents for prophylaxis and treatment of IPA in the last decade, the outcome of patients with IPA is still unsatisfactory and needs improvement. Particularly, recent developments in diagnostic imaging, including introduction of high-resolution computed tomography (CT) into standard procedures, made a place for improvement of diagnosis of IPA. Computed tomography of the chest is the optimal, recommended imaging procedure for diagnosis of pneumonia in febrile neutropenic patients and it is significantly superior to conventional chest X-ray. However, the method is associated with some difficulties mostly due to the broad spectrum of pathological findings in patients with IPA and their evolution over time. This has been described in retrospective studies on relatively small groups of patients. Prospective studies on larger populations are still missing, as well as studies on combination of different diagnostic modalities e.g. diagnostic imaging and microbiology. We recently published the results of the clinical trial: "A Phase II Dose Escalation Study of Caspofungin in Patients with Invasive Aspergillosis" which used caspofungin doses of 70 to 200 mg daily for the first line treatment of IPA. The maximum tolerated dose was not reached, but response rates were impressive with complete plus partial responses accounting for 54.3% and overall mortality at 12-week follow-up as low as 28.3%. There was a tendency towards higher doses yielding higher response rates. For the majority of these patients we obtained serial chest CT. So, for the first time a patient population is at hand, in which the kinetics of infiltrates over time can be described. The main objective is to describe the pathological findings in chest CT performed sequentially in IPA patients while receiving effective antifungal therapy. The specific objectives are: 1. Characteristics of pathological findings in sequential chest CTs - To describe the pathological findings (e.g. halo sign, air crescent sign and air consolidation) in sequential high resolution computed tomogrphy (HRCT) examinations - To calculate the incidence of individual pathological findings in sequential CT examinations - To calculate a total volume of fungal infiltrates in sequential CT examinations 2. Correlation of pathological findings in sequential CT with corresponding white blood count (WBC) and absolute neutrophil count (ANC) - To correlate the appearance or disappearance of individual pathological findings with WBC and ANC - To correlate the volume of fungal infiltrates in sequential CT examinations with WBC and absolute neutrophil count 3. Correlation of pathological findings in sequential CT with the serum galactomannan index - To correlate the appearance or disappearance of individual pathological findings with the serum galactomannan index - To correlate the volume of fungal infiltrates in sequential HRCT examinations with the serum galactomannan index 4. Correlation of pathological findings in sequential HRCT with outcome of IFI - To correlate the appearance or disappearance of individual pathological findings with outcome of IFI - To correlate the volume of fungal infiltrates in sequential HRCT examinations with outcome of IFI
Double blind, placebo controlled, ascending multiple (10) oral dose, sequential group study. Twenty-four subjects will complete the study in 3 cohorts (Groups A to C), each group consisting of 8 subjects. Each cohort will consist of 4 male and 4 female subjects. Each subject will be dosed for 10 days and will be on study for approximately 7 weeks. Each subject will participate in one treatment cohort only, residing at the Clinical Research Unit (CRU) from Day -1 (the day before dosing) to Day 15 (120 hours post the last dose). The dose will range between 2 and 10 mg/kg daily, given as either a single daily dose or as two doses divided over the 24-hour dosing period. All subjects will return for a post-study visit 8 to 10 days after the last dose of study medication. Cohorts will be dosed at least at 3 weekly intervals. There will be a review of the safety and pharmacokinetic data of each cohort prior to each dose escalation.
This will be an open label study in two parts. In the first part, F901318 (dose 2 mg/kg IV over 4 hours, Day 1) will be followed by F901318 (2 mg/kg IV over 4 hours) given on Day 8, after dosing with fluconazole 800 mg daily for 1 day (Day 4) and 400 mg daily orally for 4 days (Days 5 to 8). Up to twenty subjects will be included in two cohorts which will undergo the same dosing schedules of fluconazole and F901318 and undergo the same procedures. The first cohort will consist of 12 subjects studied in two groups of six subjects each. If there is clearly a difference in F901318 kinetics detectable before and after dosing with fluconazole in this first cohort, the second cohort will not be studied. If there is no clear difference, the second cohort will also be studied to give a final result. In this cohort, based on the pharmacokinetic findings in cohort 1, the dose of F901318 may be increased to up to 4 mg/kg to establish a dose suitable for phase 2 evaluation. PK sampling for plasma F901318 will continue from before the first dose up to and including 72 hours after dosing. PK sampling for fluconazole will continue from before the first dose and up to 72 hours after the fifth dose. A follow up visit will be conducted 7 +/- 2 days after discharge from the clinical unit following completion of blood sampling following the second dose of F901318 and the fifth dose of fluconazole. The second part of the study will take place if no appreciable change in the pharmacokinetics of either F901318 or fluconazole has been observed in either the first or the second cohorts in the first part of the study. This second part will enrol 12 subjects. These subjects will receive fluconazole 800 mg daily for one day (Day 1) and 400 mg daily orally for 4 days (Days 2 to 5) in combination with F901318 which will be given in a dose of up to 4 mg/kg IV bid for one day (Day 1) followed by 7 doses of intravenous F901318 up to 2.5 mg/kg bid (Days 2 to 5). Pharmacokinetic profiles of F901318 and fluconazole will be obtained during dosing and over a 72-hour period following the final dose of both compounds.
Open label evaluation of potential interaction of F901318 with cytochrome P450 3A4 using midazolam as a probe. Twenty healthy male subjects will participate
The objective of this study is to evaluate the efficacy and safety of intravenous micafungin for the treatment of proven or probable fungal infections caused by Aspergillus sp. (Fungemia, respiratory mycosis, gastrointestinal mycosis) in adult patients in China.
Concentrations of voriconazole in pulmonary epithelial lining fluid and in serum are compared after inhalation of 40 mg voriconazole b.i.d. for two days or oral intake of voriconazole tablets 400 mg bid for 1 day followed by 200 mg b.i.d. for one day, respectively.
Double blind, placebo controlled, ascending single oral dose, sequential group study. Forty subjects will complete the study in 5 cohorts (Groups A to E), each group consisting of 8 subjects. Each subject will be on study for approximately 6 weeks. Each subject will participate in one treatment cohort only, residing at the Clinical Research Unit (CRU) from Day -1 (the day before dosing) to Day 6 (120 hours post-dose). Each cohort will be dosed in a leading edge design in which two subjects will receive study drug (1 active and 1 placebo) on the first dosing day, and the last 6 will receive study drug (5 active and 1 placebo) on the second dosing day. All subjects will return for a post-study visit 8 to 10 days after the dose of study medication. Cohorts will be dosed at 2 weekly intervals. There will be a review of safety data, after the first two subjects have been dosed and before dosing of the subsequent six subjects. There will be a complete review of safety and pharmacokinetic data of each cohort prior to each dose escalation.