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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00412893




Registration number
NCT00412893
Ethics application status
Date submitted
18/12/2006
Date registered
19/12/2006
Date last updated
5/04/2019

Titles & IDs
Public title
Isavuconazole (BAL8557) for Primary Treatment of Invasive Aspergillosis
Scientific title
A Phase III, Double Blind, Randomized Study to Evaluate Safety and Efficacy of BAL8557 Versus Voriconazole for Primary Treatment of Invasive Fungal Disease Caused by Aspergillus Species or Other Filamentous Fungi.
Secondary ID [1] 0 0
WSA-CS-004
Secondary ID [2] 0 0
9766-CL-0104
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aspergillosis 0 0
Invasive Fungal Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Isavuconazole
Treatment: Drugs - Voriconazole

Experimental: Isavuconazole - Participants received a loading dose of isavuconazole, 200 mg three times a day by intravenous infusion (IV) for the first 2 days followed by a maintenance dose from Day 3 of 200 mg once daily either IV or orally until they reached a treatment endpoint or for a maximum of 84 days.

Active Comparator: Voriconazole - Participants received a loading dose of voriconazole, 6 mg/kg every 12 hours IV for the first 24 hours, followed by a maintenance dose of 4 mg/kg every 12 hours by IV on Day 2. Beginning on Day 3, participants received 4 mg/kg every 12 hours by IV or 200 mg every 12 hours orally, until they reached a treatment endpoint or for a maximum of 84 days.


Treatment: Drugs: Isavuconazole
Loading doses were administered as IV infusion and maintenance doses were administered as IV infusion or oral (capsules).

Treatment: Drugs: Voriconazole
Loading doses were administered as IV infusion and maintenance doses were administered as IV infusion or oral (capsules).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
All-cause Mortality Through Day 42 - All-cause mortality is represented as the percentage of participants who died after first dose of study drug through Day 42 from any cause. Participants with unknown survival status through Day 42 were included as deaths in the calculation.
Timepoint [1] 0 0
Through Day 42
Secondary outcome [1] 0 0
Percentage of Participants With an Overall Outcome of Success Evaluated by the Data Review Committee (DRC) - The DRC was an independent, blinded committee consisting of experts in the field of infectious disease who assessed patients' outcomes. The overall response was based on the DRC-assessed clinical, mycological and radiological responses.
Success was defined as the resolution or partial resolution of all attributable clinical symptoms and physical findings, the eradication or presumed eradication of the original causative organism cultured or identified by histology/cytology at Baseline and a > 50% improvement in radiological response from Baseline (or improvement of at least 25% from Baseline for the Day 42 analysis or End of Treatment if it occurred prior to Day 42).
End of treatment (EOT) is the last day of study drug administration. For the Day 42 and Day 84 analyses, any visits that the DRC assessed as Not Done were considered a failure for that visit. A death before Day 42 was also considered a failure, even if the DRC assessed the participant to be a success prior to death.
Timepoint [1] 0 0
Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary outcome [2] 0 0
All-cause Mortality Through Day 84 - All-cause mortality is represented as the percentage of participants who died after first dose of study drug through Day 84 from any cause. Participants with unknown survival status through Day 84 were included as deaths in the calculation.
Timepoint [2] 0 0
Through Day 84
Secondary outcome [3] 0 0
Percentage of Participants With an Overall Outcome of Success Evaluated by Investigator - Overall response based on investigators' assessments was not derived as it was not deemed necessary because participants overall response status was determined by the DRC. All investigators' assessments of clinical, mycological and radiological responses are analyzed separately (see Outcome Measures 8-10).
Timepoint [3] 0 0
Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary outcome [4] 0 0
Percentage of Participants With a Clinical Response Assessed by the DRC - Blinded assessments of clinical symptoms and physical findings of invasive fungal disease were performed by the independent DRC.
Clinical response is defined as the resolution or partial resolution of all attributable clinical symptoms and physical findings. Failure is defined as no resolution of any attributable clinical symptoms and physical findings and/or worsening. Participants with no attributable signs and symptoms present at Baseline and no symptoms attributable to invasive fungal disease (IFD) developed post-baseline were classified as "Not Applicable." End of treatment is the last day of study drug administration.
Timepoint [4] 0 0
Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary outcome [5] 0 0
Percentage of Participants With a Mycological Response Assessed by the DRC - Blinded mycological assessments of the participant's invasive fungal disease status were performed by the independent DRC using the results from fungal culture and isolation and/or histology/cytology of biopsy or biological fluid samples from the infected site.
Mycological response is defined as eradication or presumed eradication of the original causative organism cultured or identified by histology/cytology at Baseline. Failure was defined as persistence or presumed persistence. Participants with no mycological evidence available at Baseline were classified as "Not Applicable".
End of treatment is the last day of study drug administration.
Timepoint [5] 0 0
Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary outcome [6] 0 0
Percentage of Participants With a Radiological Response Assessed by the DRC - Independent reviews of radiology assessments were completed by radiology experts which were provided to the independent, blinded DRC. Blinded radiological assessments were performed by the DRC.
Radiological response is defined as a = 50% improvement from Baseline, or improvement of at least 25% from Baseline for the Day 42 analysis or if end of treatment occurred before Day 42. Participants without any radiology at Baseline were considered "Not Applicable." End of Treatment is the last day of study drug administration.
Timepoint [6] 0 0
Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary outcome [7] 0 0
Percentage of Participants With a Clinical Response Assessed by the Investigator - Assessment of clinical symptoms and physical findings of invasive fungal disease were performed by the investigator.
Clinical response is defined as the resolution or partial resolution of all attributable clinical symptoms and physical findings. Failure is defined as no resolution of any attributable clinical symptoms and physical findings and/or worsening, or if results were unavailable or the participant was unevaluable. Participants with no attributable signs and symptoms present at Baseline were classified as "Not Applicable." End of treatment is the last day of study drug administration.
Timepoint [7] 0 0
Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary outcome [8] 0 0
Percentage of Participants With a Mycological Response Assessed by the Investigator - Mycological assessments of the participant's invasive fungal disease status were performed by the investigator using the results from fungal culture and isolation and/or histology/cytology of biopsy or biological fluid samples from the infected site.
Mycological response is defined as eradication or presumed eradication of the original causative organism cultured or identified by histology/cytology at Baseline. Failure was defined as persistence or presumed persistence. Participants with no mycological evidence available at Baseline, or no mycological follow-up results available or indeterminate results were classified as "Not Applicable".
End of treatment is the last day of study drug administration.
Timepoint [8] 0 0
Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary outcome [9] 0 0
Percentage of Participants With a Radiological Response Assessed by the Investigator - Radiological assessments were performed by the investigator. Radiological response is defined as a = 50% improvement from Baseline, or improvement of at least 25% from Baseline for the Day 42 analysis or if end of treatment occurred before Day 42. Failure is defined as a < 25% improvement at any time or results not available. Participants with no signs on radiological images at Baseline were considered "Not Applicable." End of Treatment is the last day of study drug administration.
Timepoint [9] 0 0
Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Secondary outcome [10] 0 0
Number of Participants With Adverse Events, Reported by System Organ Class
Timepoint [10] 0 0
From the first study drug administration until 28 days after the last dose of study drug. The median duration of study drug administration was 45 days.

Eligibility
Key inclusion criteria
- Patients must have proven, probable or possible invasive fungal disease caused by
Aspergillus species or other filamentous fungi

- Female patients must be non-lactating and at no risk for pregnancy
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with invasive fungal infections other than Aspergillus species or other
filamentous fungi

- Evidence of hepatic dysfunction at Baseline or moderate to severe renal dysfunction

- Patients with chronic aspergillosis, or aspergilloma or allergic bronchopulmonary
aspergillosis

- Patients who have received more than 4 days of systemic antifungal therapy other than
fluconazole within the 7 days prior to the first administration of study medication

- Patients previously enrolled in a Phase III study with isavuconazole

- Patients with a body weight </= 40 kg

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Perth
Recruitment hospital [2] 0 0
Mater Medical Centre - South Brisbane
Recruitment hospital [3] 0 0
- Woolloongabba
Recruitment postcode(s) [1] 0 0
6000 - Perth
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
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United States of America
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Massachusetts
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United States of America
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New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
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Texas
Country [9] 0 0
Argentina
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Buenos Aires
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Argentina
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Capital Federal
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Argentina
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Ciudad Autonoma
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Belgium
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Brugge
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Belgium
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Brussels
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Belgium
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Bruxelles
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Belgium
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Gent
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Belgium
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Leuven
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Brazil
State/province [17] 0 0
Belo Horizonte
Country [18] 0 0
Brazil
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Curitiba
Country [19] 0 0
Brazil
State/province [19] 0 0
Ribeirão Preto
Country [20] 0 0
Brazil
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Rio de Janeiro
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Canada
State/province [21] 0 0
Ontario
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Canada
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Hamilton
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Chile
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Santiago
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Chile
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Temuco
Country [25] 0 0
Chile
State/province [25] 0 0
Valdivia
Country [26] 0 0
China
State/province [26] 0 0
Beijing
Country [27] 0 0
China
State/province [27] 0 0
Changchun
Country [28] 0 0
China
State/province [28] 0 0
Changsha
Country [29] 0 0
China
State/province [29] 0 0
Chengdu
Country [30] 0 0
China
State/province [30] 0 0
Fuzhou
Country [31] 0 0
China
State/province [31] 0 0
Hangzhou
Country [32] 0 0
China
State/province [32] 0 0
Nanjing
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China
State/province [33] 0 0
Nanning
Country [34] 0 0
China
State/province [34] 0 0
Shanghai
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China
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Wuhan
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Egypt
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Alexandria
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Egypt
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Cairo
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France
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Dijon
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France
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Nantes Cedex 01
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France
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Nantes Cedex
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France
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Strasbourg
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France
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Vandoeuvre les Nancy
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Germany
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Aachen
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Germany
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Berlin
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Germany
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Köln
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Germany
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Leipzig
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Germany
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Luebeck
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Germany
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Muenchen
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Germany
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Würzburg
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Hungary
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Budapest
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Hungary
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Györ
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Hungary
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Szeged
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India
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Andh Prad
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India
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Gujarat
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India
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Karna
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India
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Mahara
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India
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Uttar Prad
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Ramat-Gan
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Israel
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Tel Aviv
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Italy
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Firenze
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Italy
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Milano
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Malaysia
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Kuala Lumpur
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Mexico
State/province [68] 0 0
Mexico
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Mexico
State/province [69] 0 0
Monterrey
Country [70] 0 0
Netherlands
State/province [70] 0 0
Nijmegen
Country [71] 0 0
New Zealand
State/province [71] 0 0
Palmerston North
Country [72] 0 0
Poland
State/province [72] 0 0
Warszawa
Country [73] 0 0
Russian Federation
State/province [73] 0 0
Moscow
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Petrozavodsk
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Russian Federation
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St. Petersburg
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Spain
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Salamanca
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Switzerland
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Zurich
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Thailand
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Hat Yai
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Thailand
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Khon Kaen
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Thailand
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Muang
Country [81] 0 0
Thailand
State/province [81] 0 0
Songkla
Country [82] 0 0
Turkey
State/province [82] 0 0
Istanbul

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Astellas Pharma Inc
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Basilea Pharmaceutica International Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to compare the efficacy and safety of isavuconazole versus
voriconazole in the treatment of patients with invasive aspergillosis.
Trial website
https://clinicaltrials.gov/show/NCT00412893
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Astellas Pharma Global Development
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications