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Trial record 28 of 58 for:    "Aspergillosis" | "Cytochrome P-450 CYP3A Inhibitors"

Isavuconazole (BAL8557) for Primary Treatment of Invasive Aspergillosis

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ClinicalTrials.gov Identifier: NCT00412893
Recruitment Status : Completed
First Posted : December 19, 2006
Results First Posted : March 31, 2015
Last Update Posted : April 5, 2019
Sponsor:
Collaborator:
Basilea Pharmaceutica International Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Aspergillosis
Invasive Fungal Infection
Interventions Drug: Isavuconazole
Drug: Voriconazole
Enrollment 527
Recruitment Details Consenting adult patients with proven, probable or possible invasive fungal disease (IFD) caused by Aspergillus species or other filamentous fungi, meeting the inclusion/exclusion criteria, were enrolled in the study.
Pre-assignment Details Participants were stratified by geographic location (North America; Western Europe plus Australia and New Zealand; and Other Regions), whether or not they underwent an allogeneic bone marrow transplant (BMT) and whether or not they had uncontrolled malignancy.
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 263 264
Received Treatment 258 [1] 258
Completed 118 [2] 120 [2]
Not Completed 145 144
Reason Not Completed
Adverse Event             31             53
Death             17             21
Insufficient Therapeutic Response             39             23
Lost to Follow-up             2             1
Violation of Selection at Entry             17             10
Other Protocol Violation             10             6
Did Not Cooperate             12             9
Administrative Reason             12             15
Randomized but Never Received Study Drug             5             6
[1]
One participant randomized to this group received voriconazole treatment for the first 7 days
[2]
Defined as completed treatment
Arm/Group Title Isavuconazole Voriconazole Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 258 258 516
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population consisted of all randomized participants who received at least one administration of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 258 participants 258 participants 516 participants
51.1  (16.15) 51.2  (15.85) 51.1  (15.98)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 258 participants 258 participants 516 participants
Female
113
  43.8%
95
  36.8%
208
  40.3%
Male
145
  56.2%
163
  63.2%
308
  59.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 258 participants 516 participants
White 211 191 402
Black or African American 1 1 2
Asian 45 64 109
Other 1 1 2
Missing 0 1 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 258 participants 516 participants
Hispanic or Latino 22 9 31
Not Hispanic or Latino 236 248 484
Missing 0 1 1
Hematologic Malignancy Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 258 participants 516 participants
Yes 211 222 433
No 47 36 83
Prior Allogeneic Bone Marrow Transplant (BMT)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 258 participants 516 participants
Yes 54 51 105
No 204 207 411
[1]
Measure Description: Allogeneic BMT Status was defined as Yes for patients indicated as having a BMT, hematopoietic stem cell transplant (HSCT) or other progenitor cell transplant with type of transplant identified as allogeneic.
Uncontrolled Malignancy Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 258 participants 516 participants
Yes 173 187 360
No 85 71 156
[1]
Measure Description: Uncontrolled malignancy was defined as participants who per Investigator judgment had active malignancy (new diagnosis or relapse).
Neutropenic Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 258 participants 516 participants
Yes 163 175 338
No 95 83 178
[1]
Measure Description: The presence or absence of neutropenia was defined as an absolute neutrophil count (ANC) < 0.5 x 10^9/L (< 500/mm^3).
1.Primary Outcome
Title All-cause Mortality Through Day 42
Hide Description 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.
Time Frame Through Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 258 258
Measure Type: Number
Unit of Measure: percentage of participants
18.6 20.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Approximately 255 patients per group were to be enrolled to ensure at least 80% power to demonstrate that the upper bound of the 95% confidence interval (CI) for a treatment difference in favor of the comparator was no larger than 10%.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The upper bound of the 95% CI for the treatment difference was compared to the protocol prespecified non-inferiority margin of 10%. If the upper bound was smaller than 10%, isavuconazole was declared as non-inferior to voriconazole with respect to the primary outcome measure.
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-7.759 to 5.683
Estimation Comments The treatment difference (isavuconazole minus voriconazole) was calculated using a stratified Cochran-Mantel-Haenszel (CMH) method. The strata included Geographical Regions, Allogeneic BMT Status and Uncontrolled Malignancy Status.
2.Secondary Outcome
Title Percentage of Participants With an Overall Outcome of Success Evaluated by the Data Review Committee (DRC)
Hide Description

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.

Time Frame Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-treat (mITT) population consisted of ITT participants who had proven or probable IFD as determined by the DRC.
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 143 129
Measure Type: Number
Unit of Measure: percentage of participants
Day 42 35.7 35.7
Day 84 25.2 32.6
End of Treatment 35.0 36.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments End of Treatment comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 1.6
Confidence Interval (2-Sided) 95%
-9.336 to 12.572
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 42 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-11.277 to 10.329
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 84 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 8.2
Confidence Interval (2-Sided) 95%
-1.993 to 18.379
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
3.Secondary Outcome
Title All-cause Mortality Through Day 84
Hide Description 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.
Time Frame Through Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 258 258
Measure Type: Number
Unit of Measure: percentage of participants
29.1 31.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-9.150 to 6.340
Estimation Comments The treatment difference (isavuconazole minus voriconazole) was calculated using a stratified Cochran-Mantel-Haenszel (CMH) method. The strata included Geographical Regions, Allogeneic BMT Status and Uncontrolled Malignancy Status.
4.Secondary Outcome
Title Percentage of Participants With an Overall Outcome of Success Evaluated by Investigator
Hide Description 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).
Time Frame Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Percentage of Participants With a Clinical Response Assessed by the DRC
Hide Description

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.

Time Frame Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population. Any visits the DRC assessed as not done were considered as missing and included as a failure; participants with a Not Applicable assessment were excluded. The number of participants included in the analysis at each time point in indicated by "n".
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 143 129
Measure Type: Number
Unit of Measure: percentage of participants
Day 42 (n=139, 120) 64.0 57.5
Day 84 (n=141, 124) 46.1 44.4
End of Treatment (n=137, 121) 62.0 60.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments End of Treatment Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-10.640 to 11.531
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 42 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value -5.8
Confidence Interval (2-Sided) 95%
-17.368 to 5.802
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 84 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-11.116 to 11.758
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
6.Secondary Outcome
Title Percentage of Participants With a Mycological Response Assessed by the DRC
Hide Description

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.

Time Frame Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population. Any visits the DRC assessed as not done were considered as missing and included as a failure; participants with a Not Applicable assessment were excluded.
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 143 129
Measure Type: Number
Unit of Measure: percentage of participants
Day 42 39.9 39.5
Day 84 28.0 36.4
End of Treatment 37.8 41.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments End of Treatment comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
-7.429 to 15.087
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 42 Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-11.917 to 10.586
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 84 Comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 9.1
Confidence Interval (2-Sided) 95%
-1.624 to 19.830
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
7.Secondary Outcome
Title Percentage of Participants With a Radiological Response Assessed by the DRC
Hide Description

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.

Time Frame Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population. A participant with no post-baseline radiology data with evidence of radiologic disease at Baseline was considered a failure. Participants with a Not Applicable assessment were excluded. The number of participants included in the analysis at each time point is indicated by "n".
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 143 129
Measure Type: Number
Unit of Measure: percentage of participants
Day 42 (n=141, 128) 28.4 34.4
Day 84 (n=141, 128) 22.0 29.7
End of Treatment (n=141, 127) 29.1 33.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments End of Treatment comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 5.7
Confidence Interval (2-Sided) 95%
-4.936 to 16.268
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 42 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 5.3
Confidence Interval (2-Sided) 95%
-5.338 to 16.032
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 84 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 9.0
Confidence Interval (2-Sided) 95%
-1.231 to 19.186
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
8.Secondary Outcome
Title Percentage of Participants With a Clinical Response Assessed by the Investigator
Hide Description

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.

Time Frame Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population. Missing data for any participant at any visit was included as a failure; participants with a Not Applicable assessment were excluded. The number of participants included in the analysis at each time point in indicated by "n".
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 143 129
Measure Type: Number
Unit of Measure: percentage of participants
Day 42 (n=137, 120) 64.2 61.7
Day 84 (n=140, 122) 41.4 44.3
End of Treatment (n=137, 121) 62.0 64.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments End of Treatment comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 5.0
Confidence Interval (2-Sided) 95%
-6.043 to 16.026
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole
Comments Day 42 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted treatment Difference
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-10.873 to 11.220
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 84 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted treatment Difference
Estimated Value 4.7
Confidence Interval (2-Sided) 95%
-6.533 to 15.939
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
9.Secondary Outcome
Title Percentage of Participants With a Mycological Response Assessed by the Investigator
Hide Description

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.

Time Frame Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population. Missing data for any participant at any visit was included as a failure; participants with a Not Applicable assessment were excluded. The number of participants included in the analysis at each time point in indicated by "n".
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 143 129
Measure Type: Number
Unit of Measure: percentage of participants
Day 42 (n=109, 100) 52.3 50.0
Day 84 (n=126, 117) 35.7 37.6
End of Treatment (n=107, 100) 50.5 55.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments End of Treatment comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 4.4
Confidence Interval (2-Sided) 95%
-8.429 to 17.218
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 42 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-15.071 to 10.073
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 84 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
-8.633 to 14.499
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
10.Secondary Outcome
Title Percentage of Participants With a Radiological Response Assessed by the Investigator
Hide Description 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.
Time Frame Day 42, Day 84 and End of Treatment. The median duration of study drug administration was 45 days.
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Hide Analysis Population Description
Modified intent-to-treat population. Missing data for any participant at any visit was included as a failure. Participants with a Not Applicable assessment were excluded. The number of participants included in the analysis at each time point is indicated by "n".
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 143 129
Measure Type: Number
Unit of Measure: percentage of participants
Day 42 (n=142, 128) 45.1 51.6
Day 84 (n=141, 128) 38.3 41.4
End of Treatment (n=141, 128) 43.3 47.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments End of Treatment comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 6.3
Confidence Interval (2-Sided) 95%
-5.145 to 17.696
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 42 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 8.0
Confidence Interval (2-Sided) 95%
-3.335 to 19.356
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isavuconazole, Voriconazole
Comments Day 84 comparison
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference
Estimated Value 5.1
Confidence Interval (2-Sided) 95%
-6.187 to 16.332
Estimation Comments The adjusted treatment difference (Voriconazole-Isavuconazole) was calculated by a stratified CMH method with the strata of Geographical Region, Allogeneic BMT Status and Uncontrolled Malignancy Status.
11.Secondary Outcome
Title Number of Participants With Adverse Events, Reported by System Organ Class
Hide Description [Not Specified]
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set consists of all randomized patients who received at least one dose of study drug according to the study drug that the participant actually received as the first dose. One participant was randomized to isavuconazole but received voriconazole treatment for the first 7 days and is included in the voriconazole arm for safety.
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 257 259
Measure Type: Number
Unit of Measure: participants
Patients with ≥ 1 TEAE 247 255
Gastrointestinal Disorders 174 180
Infections and Infestations 152 158
General Disorders / Administration Site Conditions 148 144
Respiratory, Thoracic and Mediastinal Disorders 143 147
Metabolism and Nutrition Disorders 108 121
Nervous System Disorders 95 89
Skin and Subcutaneous Tissue Disorders 86 110
Investigations 85 96
Blood and Lymphatic System Disorders 77 82
Psychiatric Disorders 70 86
Musculoskeletal and Connective Tissue Disorders 69 77
Vascular Disorders 67 77
Renal and Urinary Disorders 55 58
Cardiac Disorders 43 57
Eye Disorders 39 69
Injury, Poisoning and Procedural Complications 33 39
Hepatobiliary Disorders 23 42
Immune System Disorders 20 25
Neoplasms benign, malignant and unspecified 19 31
Ear and Labyrinth Disorders 14 13
Reproductive System and Breast Disorders 8 13
Endocrine Disorders 5 3
Congenital, Familial and Genetic Disorders 3 2
Social Circumstances 0 1
Time Frame 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.
Adverse Event Reporting Description The safety analysis set consists of all randomized patients who received at least one dose of study drug according to the study drug that the participant actually received as the first dose. One participant was randomized to isavuconazole but received voriconazole treatment for the first 7 days and is included in the voriconazole arm for safety.
 
Arm/Group Title Isavuconazole Voriconazole
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Isavuconazole Voriconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Isavuconazole Voriconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   134/257 (52.14%)   149/259 (57.53%) 
Blood and lymphatic system disorders     
Agranulocytosis  1  2/257 (0.78%)  0/259 (0.00%) 
Anaemia  1  1/257 (0.39%)  2/259 (0.77%) 
Febrile neutropenia  1  14/257 (5.45%)  5/259 (1.93%) 
Haemorrhagic anaemia  1  0/257 (0.00%)  1/259 (0.39%) 
Haemorrhagic disorder  1  1/257 (0.39%)  0/259 (0.00%) 
Leukocytosis  1  1/257 (0.39%)  0/259 (0.00%) 
Microangiopathic haemolytic anaemia  1  0/257 (0.00%)  1/259 (0.39%) 
Neutropenia  1  4/257 (1.56%)  3/259 (1.16%) 
Pancytopenia  1  4/257 (1.56%)  3/259 (1.16%) 
Splenic infarction  1  1/257 (0.39%)  0/259 (0.00%) 
Thrombocytopenia  1  3/257 (1.17%)  4/259 (1.54%) 
Thrombocytopenic purpura  1  0/257 (0.00%)  1/259 (0.39%) 
Cardiac disorders     
Acute myocardial infarction  1  1/257 (0.39%)  1/259 (0.39%) 
Angina pectoris  1  0/257 (0.00%)  1/259 (0.39%) 
Arrhythmia  1  1/257 (0.39%)  0/259 (0.00%) 
Atrial fibrillation  1  1/257 (0.39%)  1/259 (0.39%) 
Cardiac arrest  1  1/257 (0.39%)  5/259 (1.93%) 
Cardio-respiratory arrest  1  2/257 (0.78%)  2/259 (0.77%) 
Cardiogenic shock  1  1/257 (0.39%)  0/259 (0.00%) 
Congestive cardiomyopathy  1  1/257 (0.39%)  0/259 (0.00%) 
Pericarditis  1  1/257 (0.39%)  0/259 (0.00%) 
Sinus bradycardia  1  1/257 (0.39%)  0/259 (0.00%) 
Supraventricular tachycardia  1  1/257 (0.39%)  0/259 (0.00%) 
Ventricular tachycardia  1  0/257 (0.00%)  2/259 (0.77%) 
Eye disorders     
Blindness unilateral  1  1/257 (0.39%)  0/259 (0.00%) 
Eyelid oedema  1  0/257 (0.00%)  1/259 (0.39%) 
Optic neuropathy  1  1/257 (0.39%)  0/259 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/257 (0.39%)  0/259 (0.00%) 
Colitis  1  1/257 (0.39%)  0/259 (0.00%) 
Constipation  1  1/257 (0.39%)  0/259 (0.00%) 
Diarrhoea  1  2/257 (0.78%)  1/259 (0.39%) 
Food poisoning  1  0/257 (0.00%)  1/259 (0.39%) 
Gastric perforation  1  1/257 (0.39%)  0/259 (0.00%) 
Gastrointestinal haemorrhage  1  0/257 (0.00%)  3/259 (1.16%) 
Gastrointestinal inflammation  1  0/257 (0.00%)  1/259 (0.39%) 
Ileus paralytic  1  0/257 (0.00%)  1/259 (0.39%) 
Intestinal haemorrhage  1  1/257 (0.39%)  1/259 (0.39%) 
Nausea  1  1/257 (0.39%)  1/259 (0.39%) 
Oesophageal ulcer  1  1/257 (0.39%)  0/259 (0.00%) 
Peritonitis  1  1/257 (0.39%)  1/259 (0.39%) 
Proctalgia  1  0/257 (0.00%)  1/259 (0.39%) 
Rectal haemorrhage  1  0/257 (0.00%)  1/259 (0.39%) 
Small intestinal obstruction  1  2/257 (0.78%)  0/259 (0.00%) 
General disorders     
Asthenia  1  1/257 (0.39%)  0/259 (0.00%) 
Chest pain  1  1/257 (0.39%)  0/259 (0.00%) 
Chills  1  1/257 (0.39%)  1/259 (0.39%) 
Death  1  1/257 (0.39%)  1/259 (0.39%) 
General physical health deterioration  1  1/257 (0.39%)  0/259 (0.00%) 
Multi-organ failure  1  1/257 (0.39%)  7/259 (2.70%) 
Pyrexia  1  8/257 (3.11%)  10/259 (3.86%) 
Sudden cardiac death  1  0/257 (0.00%)  1/259 (0.39%) 
Hepatobiliary disorders     
Cholecystitis  1  1/257 (0.39%)  0/259 (0.00%) 
Cholecystitis acute  1  0/257 (0.00%)  1/259 (0.39%) 
Hepatic failure  1  0/257 (0.00%)  2/259 (0.77%) 
Hepatic function abnormal  1  0/257 (0.00%)  2/259 (0.77%) 
Hepatitis  1  1/257 (0.39%)  0/259 (0.00%) 
Hepatitis acute  1  1/257 (0.39%)  0/259 (0.00%) 
Hyperbilirubinaemia  1  0/257 (0.00%)  2/259 (0.77%) 
Immune system disorders     
Acute graft versus host disease  1  1/257 (0.39%)  1/259 (0.39%) 
Acute graft versus host disease in intestine  1  1/257 (0.39%)  2/259 (0.77%) 
Acute graft versus host disease in liver  1  0/257 (0.00%)  1/259 (0.39%) 
Anaphylactic reaction  1  0/257 (0.00%)  2/259 (0.77%) 
Anaphylactic shock  1  1/257 (0.39%)  0/259 (0.00%) 
Hypersensitivity  1  1/257 (0.39%)  0/259 (0.00%) 
Infections and infestations     
Acinetobacter bacteraemia  1  1/257 (0.39%)  0/259 (0.00%) 
Aspergillosis  1  4/257 (1.56%)  3/259 (1.16%) 
Bacteraemia  1  0/257 (0.00%)  2/259 (0.77%) 
Bacterial sepsis  1  0/257 (0.00%)  4/259 (1.54%) 
Bronchitis pneumococcal  1  1/257 (0.39%)  0/259 (0.00%) 
Bronchopneumonia  1  1/257 (0.39%)  0/259 (0.00%) 
Bronchopulmonary aspergillosis  1  2/257 (0.78%)  1/259 (0.39%) 
Campylobacter gastroenteritis  1  0/257 (0.00%)  1/259 (0.39%) 
Catheter related infection  1  0/257 (0.00%)  1/259 (0.39%) 
Cellulitis  1  1/257 (0.39%)  1/259 (0.39%) 
Cerebral aspergillosis  1  1/257 (0.39%)  0/259 (0.00%) 
Clostridium bacteraemia  1  0/257 (0.00%)  2/259 (0.77%) 
Clostridium difficile colitis  1  1/257 (0.39%)  0/259 (0.00%) 
Cytomegalovirus infection  1  2/257 (0.78%)  2/259 (0.77%) 
Cytomegalovirus viraemia  1  1/257 (0.39%)  0/259 (0.00%) 
Diarrhoea infectious  1  0/257 (0.00%)  1/259 (0.39%) 
Empyema  1  0/257 (0.00%)  1/259 (0.39%) 
Encephalitis herpes  1  1/257 (0.39%)  0/259 (0.00%) 
Endocarditis  1  1/257 (0.39%)  0/259 (0.00%) 
Enterococcal bacteraemia  1  1/257 (0.39%)  0/259 (0.00%) 
Escherichia sepsis  1  1/257 (0.39%)  1/259 (0.39%) 
Fungal infection  1  3/257 (1.17%)  3/259 (1.16%) 
Fusarium infection  1  1/257 (0.39%)  0/259 (0.00%) 
Gastric ulcer helicobacter  1  0/257 (0.00%)  1/259 (0.39%) 
Herpes simplex  1  0/257 (0.00%)  1/259 (0.39%) 
Herpes zoster  1  0/257 (0.00%)  1/259 (0.39%) 
Infection  1  1/257 (0.39%)  0/259 (0.00%) 
Infusion site infection  1  1/257 (0.39%)  0/259 (0.00%) 
Klebsiella bacteraemia  1  1/257 (0.39%)  1/259 (0.39%) 
Klebsiella sepsis  1  1/257 (0.39%)  1/259 (0.39%) 
Lung abscess  1  0/257 (0.00%)  1/259 (0.39%) 
Meningitis  1  0/257 (0.00%)  2/259 (0.77%) 
Mucormycosis  1  1/257 (0.39%)  0/259 (0.00%) 
Muscle abscess  1  1/257 (0.39%)  0/259 (0.00%) 
Necrotising fasciitis  1  0/257 (0.00%)  1/259 (0.39%) 
Pneumonia  1  5/257 (1.95%)  10/259 (3.86%) 
Pneumonia bacterial  1  0/257 (0.00%)  1/259 (0.39%) 
Pneumonia moraxella  1  1/257 (0.39%)  0/259 (0.00%) 
Pneumonia pneumococcal  1  0/257 (0.00%)  1/259 (0.39%) 
Pneumonia staphylococcal  1  0/257 (0.00%)  1/259 (0.39%) 
Pseudomonal bacteraemia  1  0/257 (0.00%)  1/259 (0.39%) 
Pseudomonal sepsis  1  1/257 (0.39%)  1/259 (0.39%) 
Pseudomonas infection  1  0/257 (0.00%)  1/259 (0.39%) 
Pyothorax  1  0/257 (0.00%)  1/259 (0.39%) 
Respiratory tract infection  1  1/257 (0.39%)  0/259 (0.00%) 
Sepsis  1  7/257 (2.72%)  8/259 (3.09%) 
Sepsis syndrome  1  1/257 (0.39%)  0/259 (0.00%) 
Septic shock  1  14/257 (5.45%)  10/259 (3.86%) 
Skin infection  1  1/257 (0.39%)  0/259 (0.00%) 
Staphylococcal bacteraemia  1  0/257 (0.00%)  3/259 (1.16%) 
Staphylococcal infection  1  1/257 (0.39%)  0/259 (0.00%) 
Staphylococcal sepsis  1  0/257 (0.00%)  2/259 (0.77%) 
Stenotrophomonas sepsis  1  0/257 (0.00%)  1/259 (0.39%) 
Systemic candida  1  0/257 (0.00%)  1/259 (0.39%) 
Toxoplasmosis  1  0/257 (0.00%)  1/259 (0.39%) 
Tuberculosis  1  0/257 (0.00%)  1/259 (0.39%) 
Urinary tract infection  1  1/257 (0.39%)  1/259 (0.39%) 
Urinary tract infection bacterial  1  0/257 (0.00%)  1/259 (0.39%) 
Injury, poisoning and procedural complications     
Accident at home  1  0/257 (0.00%)  1/259 (0.39%) 
Drug toxicity  1  2/257 (0.78%)  0/259 (0.00%) 
Fall  1  1/257 (0.39%)  0/259 (0.00%) 
Femoral neck fracture  1  0/257 (0.00%)  1/259 (0.39%) 
Radius fracture  1  0/257 (0.00%)  1/259 (0.39%) 
Investigations     
Alanine aminotransferase increased  1  0/257 (0.00%)  1/259 (0.39%) 
Aspartate aminotransferase increased  1  0/257 (0.00%)  1/259 (0.39%) 
Blood alkaline phosphatase increased  1  0/257 (0.00%)  1/259 (0.39%) 
Blood bilirubin increased  1  0/257 (0.00%)  1/259 (0.39%) 
Blood sodium decreased  1  1/257 (0.39%)  0/259 (0.00%) 
Electrocardiogram QT prolonged  1  0/257 (0.00%)  1/259 (0.39%) 
Haemoglobin decreased  1  1/257 (0.39%)  0/259 (0.00%) 
Hepatic enzyme increased  1  0/257 (0.00%)  1/259 (0.39%) 
Liver function test abnormal  1  1/257 (0.39%)  1/259 (0.39%) 
Metabolism and nutrition disorders     
Dehydration  1  0/257 (0.00%)  2/259 (0.77%) 
Diabetes mellitus inadequate control  1  1/257 (0.39%)  0/259 (0.00%) 
Failure to thrive  1  1/257 (0.39%)  0/259 (0.00%) 
Hypernatraemia  1  0/257 (0.00%)  1/259 (0.39%) 
Hypoglycaemia  1  0/257 (0.00%)  1/259 (0.39%) 
Hypokalaemia  1  0/257 (0.00%)  1/259 (0.39%) 
Hypophagia  1  0/257 (0.00%)  1/259 (0.39%) 
Metabolic acidosis  1  0/257 (0.00%)  2/259 (0.77%) 
Musculoskeletal and connective tissue disorders     
Muscle haemorrhage  1  1/257 (0.39%)  0/259 (0.00%) 
Musculoskeletal chest pain  1  1/257 (0.39%)  0/259 (0.00%) 
Myositis  1  1/257 (0.39%)  0/259 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute leukaemia  1  0/257 (0.00%)  1/259 (0.39%) 
Acute lymphocytic leukaemia  1  0/257 (0.00%)  1/259 (0.39%) 
Acute lymphocytic leukaemia recurrent  1  1/257 (0.39%)  1/259 (0.39%) 
Acute myeloid leukaemia  1  3/257 (1.17%)  8/259 (3.09%) 
Acute myeloid leukaemia recurrent  1  0/257 (0.00%)  5/259 (1.93%) 
B-cell lymphoma  1  0/257 (0.00%)  1/259 (0.39%) 
B-cell lymphoma recurrent  1  0/257 (0.00%)  1/259 (0.39%) 
Blast cell crisis  1  1/257 (0.39%)  1/259 (0.39%) 
Burkitt's leukaemia  1  0/257 (0.00%)  1/259 (0.39%) 
Chronic lymphocytic leukaemia  1  0/257 (0.00%)  2/259 (0.77%) 
Chronic lymphocytic leukaemia recurrent  1  1/257 (0.39%)  0/259 (0.00%) 
Endometrial cancer  1  1/257 (0.39%)  0/259 (0.00%) 
Epstein-Barr virus associated lymphoproliferative disorder  1  0/257 (0.00%)  1/259 (0.39%) 
Leukaemia  1  0/257 (0.00%)  1/259 (0.39%) 
Lung neoplasm malignant  1  0/257 (0.00%)  1/259 (0.39%) 
Lymphoma  1  2/257 (0.78%)  1/259 (0.39%) 
Malignant neoplasm progression  1  1/257 (0.39%)  1/259 (0.39%) 
Metastases to bone  1  0/257 (0.00%)  1/259 (0.39%) 
Metastases to meninges  1  1/257 (0.39%)  0/259 (0.00%) 
Metastatic pain  1  0/257 (0.00%)  1/259 (0.39%) 
Multiple myeloma  1  2/257 (0.78%)  0/259 (0.00%) 
Myelodysplastic syndrome  1  1/257 (0.39%)  0/259 (0.00%) 
Myeloid leukaemia  1  1/257 (0.39%)  1/259 (0.39%) 
Neoplasm progression  1  1/257 (0.39%)  1/259 (0.39%) 
Non-Hodgkin's lymphoma  1  1/257 (0.39%)  0/259 (0.00%) 
Primary effusion lymphoma  1  1/257 (0.39%)  0/259 (0.00%) 
Nervous system disorders     
Aphasia  1  0/257 (0.00%)  1/259 (0.39%) 
Brain stem stroke  1  1/257 (0.39%)  0/259 (0.00%) 
Central nervous system lesion  1  1/257 (0.39%)  1/259 (0.39%) 
Cerebral haemorrhage  1  0/257 (0.00%)  1/259 (0.39%) 
Cerebral ischaemia  1  1/257 (0.39%)  0/259 (0.00%) 
Convulsion  1  3/257 (1.17%)  1/259 (0.39%) 
Dizziness  1  0/257 (0.00%)  1/259 (0.39%) 
Encephalitis  1  0/257 (0.00%)  1/259 (0.39%) 
Encephalopathy  1  1/257 (0.39%)  1/259 (0.39%) 
Epilepsy  1  2/257 (0.78%)  1/259 (0.39%) 
Febrile convulsion  1  1/257 (0.39%)  0/259 (0.00%) 
Grand mal convulsion  1  0/257 (0.00%)  1/259 (0.39%) 
Haemorrhage intracranial  1  2/257 (0.78%)  3/259 (1.16%) 
Headache  1  1/257 (0.39%)  0/259 (0.00%) 
Hemiplegia  1  0/257 (0.00%)  1/259 (0.39%) 
Ischaemic stroke  1  1/257 (0.39%)  1/259 (0.39%) 
Neurotoxicity  1  1/257 (0.39%)  0/259 (0.00%) 
Paraplegia  1  1/257 (0.39%)  1/259 (0.39%) 
Polyneuropathy  1  2/257 (0.78%)  0/259 (0.00%) 
Stupor  1  0/257 (0.00%)  1/259 (0.39%) 
Subarachnoid haemorrhage  1  0/257 (0.00%)  1/259 (0.39%) 
Tremor  1  0/257 (0.00%)  1/259 (0.39%) 
VIIth nerve paralysis  1  0/257 (0.00%)  1/259 (0.39%) 
Psychiatric disorders     
Confusional state  1  0/257 (0.00%)  1/259 (0.39%) 
Depressed mood  1  0/257 (0.00%)  1/259 (0.39%) 
Depression  1  1/257 (0.39%)  0/259 (0.00%) 
Hallucination  1  0/257 (0.00%)  1/259 (0.39%) 
Hallucination, visual  1  0/257 (0.00%)  2/259 (0.77%) 
Mental status changes  1  0/257 (0.00%)  2/259 (0.77%) 
Suicide attempt  1  0/257 (0.00%)  1/259 (0.39%) 
Renal and urinary disorders     
Haematuria  1  1/257 (0.39%)  0/259 (0.00%) 
Renal failure  1  3/257 (1.17%)  2/259 (0.77%) 
Renal failure acute  1  6/257 (2.33%)  8/259 (3.09%) 
Respiratory, thoracic and mediastinal disorders     
Acute lung injury  1  0/257 (0.00%)  1/259 (0.39%) 
Acute respiratory distress syndrome  1  0/257 (0.00%)  2/259 (0.77%) 
Acute respiratory failure  1  5/257 (1.95%)  5/259 (1.93%) 
Bronchopleural fistula  1  1/257 (0.39%)  0/259 (0.00%) 
Bronchospasm  1  1/257 (0.39%)  0/259 (0.00%) 
Chronic obstructive pulmonary disease  1  0/257 (0.00%)  1/259 (0.39%) 
Cough  1  0/257 (0.00%)  1/259 (0.39%) 
Dyspnoea  1  5/257 (1.95%)  1/259 (0.39%) 
Epistaxis  1  0/257 (0.00%)  4/259 (1.54%) 
Haemoptysis  1  2/257 (0.78%)  2/259 (0.77%) 
Haemothorax  1  0/257 (0.00%)  1/259 (0.39%) 
Hydropneumothorax  1  1/257 (0.39%)  0/259 (0.00%) 
Hypoxia  1  2/257 (0.78%)  1/259 (0.39%) 
Lung disorder  1  1/257 (0.39%)  1/259 (0.39%) 
Lung infiltration  1  0/257 (0.00%)  3/259 (1.16%) 
Pleural effusion  1  1/257 (0.39%)  1/259 (0.39%) 
Pleuritic pain  1  1/257 (0.39%)  0/259 (0.00%) 
Pneumonia aspiration  1  1/257 (0.39%)  0/259 (0.00%) 
Pneumothorax  1  0/257 (0.00%)  1/259 (0.39%) 
Productive cough  1  0/257 (0.00%)  1/259 (0.39%) 
Pulmonary embolism  1  0/257 (0.00%)  3/259 (1.16%) 
Pulmonary haemorrhage  1  2/257 (0.78%)  1/259 (0.39%) 
Pulmonary hypertension  1  0/257 (0.00%)  1/259 (0.39%) 
Pulmonary oedema  1  1/257 (0.39%)  1/259 (0.39%) 
Respiratory acidosis  1  1/257 (0.39%)  0/259 (0.00%) 
Respiratory arrest  1  0/257 (0.00%)  1/259 (0.39%) 
Respiratory depression  1  1/257 (0.39%)  1/259 (0.39%) 
Respiratory distress  1  4/257 (1.56%)  3/259 (1.16%) 
Respiratory failure  1  14/257 (5.45%)  12/259 (4.63%) 
Tachypnoea  1  1/257 (0.39%)  0/259 (0.00%) 
Skin and subcutaneous tissue disorders     
Decubitus ulcer  1  1/257 (0.39%)  0/259 (0.00%) 
Dermatitis  1  1/257 (0.39%)  0/259 (0.00%) 
Panniculitis  1  1/257 (0.39%)  0/259 (0.00%) 
Rash  1  0/257 (0.00%)  2/259 (0.77%) 
Vascular disorders     
Deep vein thrombosis  1  0/257 (0.00%)  1/259 (0.39%) 
Haemorrhage  1  1/257 (0.39%)  1/259 (0.39%) 
Hypotension  1  1/257 (0.39%)  2/259 (0.77%) 
Hypovolaemic shock  1  1/257 (0.39%)  1/259 (0.39%) 
Shock  1  0/257 (0.00%)  1/259 (0.39%) 
Vasculitis  1  1/257 (0.39%)  0/259 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Isavuconazole Voriconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   227/257 (88.33%)   228/259 (88.03%) 
Blood and lymphatic system disorders     
Anaemia  1  11/257 (4.28%)  22/259 (8.49%) 
Febrile neutropenia  1  19/257 (7.39%)  34/259 (13.13%) 
Thrombocytopenia  1  10/257 (3.89%)  22/259 (8.49%) 
Cardiac disorders     
Tachycardia  1  12/257 (4.67%)  21/259 (8.11%) 
Eye disorders     
Visual impairment  1  4/257 (1.56%)  19/259 (7.34%) 
Gastrointestinal disorders     
Abdominal pain  1  24/257 (9.34%)  36/259 (13.90%) 
Abdominal pain upper  1  15/257 (5.84%)  25/259 (9.65%) 
Constipation  1  35/257 (13.62%)  54/259 (20.85%) 
Diarrhoea  1  59/257 (22.96%)  59/259 (22.78%) 
Dyspepsia  1  15/257 (5.84%)  13/259 (5.02%) 
Nausea  1  70/257 (27.24%)  78/259 (30.12%) 
Vomiting  1  64/257 (24.90%)  73/259 (28.19%) 
General disorders     
Asthenia  1  15/257 (5.84%)  20/259 (7.72%) 
Chills  1  27/257 (10.51%)  22/259 (8.49%) 
Fatigue  1  27/257 (10.51%)  18/259 (6.95%) 
Mucosal inflammation  1  23/257 (8.95%)  14/259 (5.41%) 
Oedema  1  13/257 (5.06%)  18/259 (6.95%) 
Oedema peripheral  1  26/257 (10.12%)  31/259 (11.97%) 
Pyrexia  1  53/257 (20.62%)  72/259 (27.80%) 
Infections and infestations     
Cytomegalovirus infection  1  15/257 (5.84%)  21/259 (8.11%) 
Oral herpes  1  13/257 (5.06%)  14/259 (5.41%) 
Investigations     
Alanine aminotransferase increased  1  13/257 (5.06%)  17/259 (6.56%) 
Aspartate aminotransferase increased  1  11/257 (4.28%)  14/259 (5.41%) 
Blood alkaline phosphatase increased  1  12/257 (4.67%)  14/259 (5.41%) 
Gamma-glutamyltransferase increased  1  16/257 (6.23%)  22/259 (8.49%) 
Metabolism and nutrition disorders     
Decreased appetite  1  22/257 (8.56%)  28/259 (10.81%) 
Hyperglycaemia  1  10/257 (3.89%)  13/259 (5.02%) 
Hypokalaemia  1  45/257 (17.51%)  55/259 (21.24%) 
Hypomagnesaemia  1  14/257 (5.45%)  27/259 (10.42%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  26/257 (10.12%)  19/259 (7.34%) 
Pain in extremity  1  11/257 (4.28%)  15/259 (5.79%) 
Nervous system disorders     
Dizziness  1  10/257 (3.89%)  14/259 (5.41%) 
Headache  1  40/257 (15.56%)  38/259 (14.67%) 
Psychiatric disorders     
Anxiety  1  20/257 (7.78%)  17/259 (6.56%) 
Confusional state  1  16/257 (6.23%)  19/259 (7.34%) 
Insomnia  1  23/257 (8.95%)  24/259 (9.27%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  33/257 (12.84%)  34/259 (13.13%) 
Dyspnoea  1  30/257 (11.67%)  28/259 (10.81%) 
Epistaxis  1  21/257 (8.17%)  25/259 (9.65%) 
Haemoptysis  1  14/257 (5.45%)  16/259 (6.18%) 
Oropharyngeal pain  1  14/257 (5.45%)  14/259 (5.41%) 
Rales  1  5/257 (1.95%)  14/259 (5.41%) 
Skin and subcutaneous tissue disorders     
Erythema  1  9/257 (3.50%)  15/259 (5.79%) 
Pruritus  1  19/257 (7.39%)  15/259 (5.79%) 
Rash  1  17/257 (6.61%)  26/259 (10.04%) 
Vascular disorders     
Hypertension  1  25/257 (9.73%)  31/259 (11.97%) 
Hypotension  1  20/257 (7.78%)  26/259 (10.04%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site’s manuscript at least 30 days prior to publication for review and comment. Sponsor may delay the publication for up to 60 days to seek patent protection.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Head Immunology, Transplant and Infectious Disease Therapeutic Area
Organization: Astellas Pharma Global Development, Inc.
EMail: resultsdisclosure@astellas.com
Layout table for additonal information
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00412893     History of Changes
Other Study ID Numbers: 9766-CL-0104
WSA-CS-004 ( Other Identifier: Basilea Protocol ID )
2006-003868-59 ( EudraCT Number )
First Submitted: December 18, 2006
First Posted: December 19, 2006
Results First Submitted: March 19, 2015
Results First Posted: March 31, 2015
Last Update Posted: April 5, 2019