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Isavuconazole (BAL8557) in the Treatment of Candidemia and Other Invasive Candida Infections

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ClinicalTrials.gov Identifier: NCT00413218
Recruitment Status : Completed
First Posted : December 19, 2006
Results First Posted : August 1, 2017
Last Update Posted : February 15, 2019
Sponsor:
Collaborator:
Basilea Pharmaceutica
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 Candidiasis, Invasive
Candidemia
Mycoses
Interventions Drug: Isavuconazole
Drug: Caspofungin
Drug: Voriconazole
Enrollment 450
Recruitment Details Consenting male and female participants ≥ 18 with candidemia or an invasive Candida infection who had a positive blood or tissue culture obtained within 96 hours prior to randomization and meeting the inclusion/exclusion criteria were enrolled in the study.
Pre-assignment Details Participants were stratified at randomization by geographical region and baseline neutropenic status.
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Hide Arm/Group Description Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily. Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
Period Title: Overall Study
Started [1] 223 227
Intent to Treat Population (ITT) [2] 221 219
Completed 120 131
Not Completed 103 96
Reason Not Completed
Randomized but didn't receive study drug             2             8
Death             57             56
Lost to Follow-up             14             17
Admin             20             14
Missing             1             0
Withdrawal by Subject             9             1
[1]
Four hundred and fifty participants were randomized but 10 participants did not receive treatment.
[2]
The ITT consisted of all randomized participants who received at least one dose of study drug.
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole Total
Hide Arm/Group Description Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily. Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter. Total of all reporting groups
Overall Number of Baseline Participants 221 219 440
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Geometric Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 221 participants 219 participants 440 participants
58.0  (17.54) 57.9  (16.88) 58.0  (17.20)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 221 participants 219 participants 440 participants
Female
78
  35.3%
93
  42.5%
171
  38.9%
Male
143
  64.7%
126
  57.5%
269
  61.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 221 participants 219 participants 440 participants
White
150
  67.9%
144
  65.8%
294
  66.8%
Black or African American
11
   5.0%
7
   3.2%
18
   4.1%
Asian
56
  25.3%
64
  29.2%
120
  27.3%
Other
4
   1.8%
4
   1.8%
8
   1.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 221 participants 219 participants 440 participants
Hispanic or Latino
26
  11.8%
19
   8.7%
45
  10.2%
Not Hispanic or Latino
187
  84.6%
195
  89.0%
382
  86.8%
Missing
8
   3.6%
5
   2.3%
13
   3.0%
Neutropenic Status: Presence or Absence of Neutropenia   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 221 participants 219 participants 440 participants
Presence
25
  11.3%
24
  11.0%
49
  11.1%
Absence
196
  88.7%
195
  89.0%
391
  88.9%
[1]
Measure Description: Participants were stratified by baseline neutropenic status (presence vs absence of neutropenia) defined as absolute neutrophil count (ANC) < 0.5 x 10^9/L [< 500/mm^3] for ≥ 10 days.
Geographical Region   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 221 participants 219 participants 440 participants
North America
38
  17.2%
33
  15.1%
71
  16.1%
Western Europe
54
  24.4%
56
  25.6%
110
  25.0%
Other Regions
129
  58.4%
130
  59.4%
259
  58.9%
[1]
Measure Description: Participants were stratified at randomization by geographical region. The region Western Europe includes countries in Western Europe (Belgium, France, Germany, Italy, Spain and Switzerland), Australia and New Zealand. Other regions include countries Argentina, Brazil, Chile, China, Hungary, India, Israel, Lebanon, Malaysia, Mexico, Philippines, South Africa, Russia, Singapore and Thailand.
1.Primary Outcome
Title Percentage of Participants With Overall Response of Success at the End of Intravenous Therapy (EOIV) as Determined by the Data Review Committee (DRC) Based on the Assessments of Clinical and Mycological Responses as Well as Alternative Systemic AFT Use
Hide Description A Data Review Committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial) and mycological response (eradication or presumed eradication) without the use of alternative systemic antifungal therapy (AFT) within 48 hours after the last dose of IV study medication.
Time Frame End of Intravenous Treatment (EOIV) (Days 11-56)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participants who received at least one dose of study drug. The mITT population consisted of ITT participants who had documented invasive candidiasis or candidemia at baseline based on the assessment of the independent blinded DRC. Reporting arms included participants who switched to oral ISA and CAS.
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Hide Arm/Group Description:
Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily.
Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
Overall Number of Participants Analyzed 199 201
Measure Type: Number
Unit of Measure: Percentage of Participants
60.3 71.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments The adjusted treatment difference (ISA-CAS) was calculated by a stratified Cochran-Mantel-Haenszel (CMH) method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Non-Inferiority
Comments The lower bound of the 95% CI for the adjusted treatment difference was compared to the protocol prespecified noninferiority margin (NIM) value of -15%. If the lower bound were greater than -15%, isavuconazole would be declared as noninferior to caspofungin.
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -10.8
Confidence Interval (2-Sided) 95%
-19.9 to -1.8
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
2.Secondary Outcome
Title Percentage of Participants With Overall Response of Success at Follow Up Visit 1 (FU1-2 Weeks After End of Treatment (EOT)) as Determined by the DRC Based on the Assessments of Clinical, Mycological Responses and Antifungal Therapy (AFT)
Hide Description A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial) and mycological response (eradication or presumed eradication), without the use of alternative systemic AFT within 48 hours after the last dose of IV study medication.
Time Frame End of Treatment (EOT) (Day 56) and FU1 (2 weeks after end of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT was the primary efficacy population and it consisted of ITT participants who had documented invasive candidiasis or candidemia at baseline based on the assessment of the independent blinded DRC. The isavuconazole and caspofungin group included participants who switched to oral isavuconazol and voriconazole.
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Hide Arm/Group Description:
Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily.
Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
Overall Number of Participants Analyzed 199 201
Measure Type: Number
Unit of Measure: Percentage of Participants
54.8 57.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -2.7
Confidence Interval (2-Sided) 95%
-12.2 to 6.8
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
3.Secondary Outcome
Title Percentage of Participants With Overall Response of Success at EOT and Follow Up Visit 2 (FU2) as Determined by the DRC Based on the Assessments of Clinical and Mycological Responses as Well as Alternative Systemic AFT Use at EOT and FU2
Hide Description A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial) and mycological response (eradication or presumed eradication), without the use of alternative systemic antifungal therapy AFT within 48 hours after the last dose of IV study medication (for EOT analysis) or for continued treatment of the primary infection, or for recurrent or emergent infection by FU2, with no recurrent or emergent infection by FU2 (for FU2 analysis).
Time Frame EOT (Day 56) and FU2 (6 weeks after end of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT was the primary efficacy population and it consisted of ITT participants who had documented invasive candidiasis or candidemia at baseline based on the assessment of the independent blinded DRC. The isavuconazole and caspofungin group included participants who switched to oral isavuconazol and voriconazole.
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Hide Arm/Group Description:
Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily.
Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
Overall Number of Participants Analyzed 199 201
Measure Type: Number
Unit of Measure: Percentage of Participants
EOT (Day 56) 61.3 72.1
FU2 (6 weeks after end of treatment) 43.2 48.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at EOT (Day 56). The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference %
Estimated Value -10.9
Confidence Interval (2-Sided) 95%
-19.9 to -1.9
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at FU2 (6 weeks after end of treatment). The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference %
Estimated Value -5.4
Confidence Interval (2-Sided) 95%
-15.00 to 4.2
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
4.Secondary Outcome
Title Percentage of Participants With Clinical Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC)
Hide Description A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as clinical response (complete or partial).
Time Frame EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT was the primary efficacy population and it consisted of ITT participants who had documented invasive candidiasis or candidemia at baseline based on the assessment of the independent blinded DRC. The isavuconazole and caspofungin group included participants who switched to oral isavuconazol and voriconazole.
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Hide Arm/Group Description:
Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily.
Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
Overall Number of Participants Analyzed 199 201
Measure Type: Number
Unit of Measure: Percentage of Participants
Success- End of Intravenous Treatment (EOIV) 76.4 84.1
Success- End of Treatment (EOT) 76.4 84.6
Success- Follow-up Visit 1 (FU1) 67.8 67.7
Success- Follow-up Visit 2 (FU2) 52.8 58.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at EOIV (Days 11-56).The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -8.2
Confidence Interval (2-Sided) 95%
-15.4 to -0.9
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at EOT (Day 56). The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -8.6
Confidence Interval (2-Sided) 95%
-15.8 to -1.5
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at FU1 (2 weeks after end of treatment). The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-9.1 to 8.3
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at FU2 (6 weeks after end of treatment).The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -5.8
Confidence Interval (2-Sided) 95%
-15.3 to 3.6
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
5.Secondary Outcome
Title Percentage of Participants With Mycological Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC)
Hide Description A data review committee (DRC) was established from independent experts in the field of fungal infections to determine diagnosis and outcomes independently of the investigators and sponsor. Success was defined as mycological response (Eradication or Presumed Eradication).
Time Frame EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT was the primary efficacy population and it consisted of ITT participants who had documented invasive candidiasis or candidemia at baseline based on the assessment of the independent blinded DRC. The isavuconazole and caspofungin group included participants who switched to oral isavuconazol and voriconazole.
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Hide Arm/Group Description:
Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily.
Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
Overall Number of Participants Analyzed 199 201
Measure Type: Number
Unit of Measure: Percentage of Participants
Success-EOIV 70.9 85.6
Success-EOT 71.9 87.6
Success-FU1 66.8 65.7
Success-FU2 51.8 56.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at EOIV (Days 11-56). The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -14.9
Confidence Interval (2-Sided) 95%
-22.7 to -7.0
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at EOT (Day 56). The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -15.9
Confidence Interval (2-Sided) 95%
-23.5 to -8.4
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at FU1 (2 weeks after end of treatment).The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-8.1 to 9.6
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at FU2 (6 weeks after end of treatment).The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -5.2
Confidence Interval (2-Sided) 95%
-14.7 to 4.3
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
6.Secondary Outcome
Title Percentage of Participants With Mycological Response of Success at Day 7 and EOT as Determined by The Investigator
Hide Description Success was defined as mycological response (eradication or presumed eradication).
Time Frame Day 7 and EOT (Day 56)
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT was the primary efficacy population and it consisted of ITT participants who had documented invasive candidiasis or candidemia at baseline based on the assessment of the independent blinded DRC. The isavuconazole and caspofungin group included participants who switched to oral isavuconazol and voriconazole.
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Hide Arm/Group Description:
Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily.
Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
Overall Number of Participants Analyzed 199 201
Measure Type: Number
Unit of Measure: Percentage of Participants
Day 7 61.3 72.1
EOT 72.9 81.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at Day 7. The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -11.4
Confidence Interval (2-Sided) 95%
-20.4 to -2.5
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at EOT (Day 56). The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -8.5
Confidence Interval (2-Sided) 95%
-16.5 to -0.4
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
7.Secondary Outcome
Title Percentage of Participants With Clinical Response of Success at Day 7 and EOT as Determined by The Investigator
Hide Description Investigators defined clinical response as success if participants exhibited complete or partial clinical response after evaluation of clinical signs and symptoms.
Time Frame Day 7 and EOT (Day 56)
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT was the primary efficacy population and it consisted of ITT participants who had documented invasive candidiasis or candidemia at baseline based on the assessment of the independent blinded DRC. The isavuconazole and caspofungin group included participants who switched to oral isavuconazol and voriconazole
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Hide Arm/Group Description:
Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic participants could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole once daily.
Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
Overall Number of Participants Analyzed 199 201
Measure Type: Number
Unit of Measure: Percentage of Participants
Day 7 54.3 64.7
EOT 70.9 78.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at Day 7. The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -11.1
Confidence Interval (2-Sided) 95%
-20.3 to -1.9
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of adjusted treatment difference (ISA-CAS) at EOT (Day 56). The adjusted treatment difference (ISA-CAS) was calculated by a stratified CMH method with the strata of geographical region and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value -8.1
Confidence Interval (2-Sided) 95%
-16.3 to 0.1
Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
8.Secondary Outcome
Title All-Cause Mortality (ACM) at Day 14 and Day 56
Hide Description All-cause mortality is represented as the percentage of participants who died on or before the analysis day. Participants who were lost to follow-up (i.e., unknown survival status) before the analysis day were counted as death. All-cause mortality was examined on Day 14 and Day 56.
Time Frame Day 14 and Day 56
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT was the primary efficacy population and it consisted of ITT participants who had documented invasive candidiasis or candidemia at baseline based on the assessment of the independent blinded DRC.
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Hide Arm/Group Description:
Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily.
Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
Overall Number of Participants Analyzed 199 201
Measure Type: Number
Unit of Measure: Percentage of Participants
Day 14 All-cause Mortality 14.6 12.4
Day 56 All-cause Mortality 30.7 29.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of all-cause mortality on Day 14. Adjusted treatment difference (Isavuconazole-Caspofungin) is calculated by a stratified CMH method with the strata of geographical regions, and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value 2.5
Confidence Interval (2-Sided) 95%
-3.8 to 8.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Isavuconazole (ISA), Caspofungin (CAS)/Voriconazole
Comments Statistical analysis of all-cause mortality on Day 56. Adjusted treatment difference (Isavuconazole-Caspofungin) is calculated by a stratified CMH method with the strata of geographical regions, and baseline neutropenic status.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-7.1 to 10.0
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time to First Confirmed Negative Culture
Hide Description The first confirmed negative blood culture was defined as the first negative blood culture on or after first dose followed by a second negative blood culture at least 24 hours apart without any positive blood cultures in between. A participant without a confirmed negative blood culture was censored on the participant’s last visit day. This endpoint was analyzed for mITT participants with candidemia only using the Kaplan-Meier method. Only participants with at least one positive blood culture on or prior to first dose and the culture not resolved prior to first dose were included in this analysis
Time Frame Day 1 up to FU1 (2 weeks after EOT (Day 56))
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT was the primary efficacy population and it consisted of ITT participants who had documented invasive candidiasis or candidemia at baseline based on the assessment of the independent blinded DRC.
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Hide Arm/Group Description:
Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole twice daily.
Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
Overall Number of Participants Analyzed 120 119
Median (95% Confidence Interval)
Unit of Measure: Days
4.0
(3.0 to 6.0)
3.0
(3.0 to 4.0)
Time Frame Day 1 to FU2 (6 weeks after EOT (Day 56))
Adverse Event Reporting Description Treatment-emergent adverse events (TEAE) are AEs which started after the first use of study drug until FU2, and are based on the Safety Analysis Set (SAF) population. The SAF consisted of all participants who received at least one dose of study drug. SAF data were analyzed according to the first dose of study drug participants received even if it was different from what they were randomized to. One participant randomized to ISA received CAS on Day 1 and was included in CAS group for safety.
 
Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Hide Arm/Group Description Participants received 3 intravenous (IV) loading doses of 200 mg of isavuconazole on days 1 and 2, followed by an IV maintenance dose of 200 mg once daily from day 3 to day 56. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV to oral therapy. Oral therapy consisted of 200 mg isavuconazole once daily. Participants received 1 intravenous (IV) loading dose of 70 mg CAS on day 1, followed by an IV maintenance dose of 50 mg CAS from day 2 to day 56. Participants with body weight > 80 kg received 70 mg CAS daily. On day 11 at the discretion of the investigator, non-neutropenic patients could switch from IV CAS to oral voriconazole comprising of a loading dose of 400 mg twice daily (BID) on the first day of oral therapy followed by standard dosing of 200 mg BID thereafter.
All-Cause Mortality
Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   55/220 (25.00%)      55/220 (25.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   112/220 (50.91%)      106/220 (48.18%)    
Blood and lymphatic system disorders     
Anaemia  1  1/220 (0.45%)  1 3/220 (1.36%)  3
Anaemia haemolytic autoimmune  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Coagulopathy  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Disseminated intravascular coagulation  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Neutropenia  1  1/220 (0.45%)  1 2/220 (0.91%)  2
Pancytopenia  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Thrombocytopenia  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Cardiac disorders     
Arrhythmia  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Atrial fibrillation  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Bradycardia  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Cardiac arrest  1  4/220 (1.82%)  6 6/220 (2.73%)  6
Cardiac failure  1  0/220 (0.00%)  0 2/220 (0.91%)  2
Cardio-respiratory arrest  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Cardiomyopathy  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Coronary artery stenosis  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Hypertensive heart disease  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Myocardial infarction  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Pericardial effusion  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Sick sinus syndrome  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Tachycardia  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Torsade de pointes  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Ventricular extrasystoles  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Ventricular fibrillation  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Ventricular tachycardia  1  2/220 (0.91%)  2 0/220 (0.00%)  0
Congenital, familial and genetic disorders     
Sickle cell anaemia with crisis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Endocrine disorders     
Diabetes insipidus  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Eye disorders     
Vision blurred  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Gastrointestinal disorders     
Abdominal distension  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Abdominal pain  1  0/220 (0.00%)  0 2/220 (0.91%)  3
Ascites  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Diarrhoea  1  2/220 (0.91%)  2 0/220 (0.00%)  0
Duodenal perforation  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Enterocutaneous fistula  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Faecaloma  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Gastrointestinal haemorrhage  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Intestinal obstruction  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Intestinal perforation  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Lower gastrointestinal haemorrhage  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Melaena  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Nausea  1  1/220 (0.45%)  1 2/220 (0.91%)  2
Pancreatitis  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Peritonitis  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Proctalgia  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Rectal haemorrhage  1  0/220 (0.00%)  0 1/220 (0.45%)  2
Upper gastrointestinal haemorrhage  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Vomiting  1  1/220 (0.45%)  1 3/220 (1.36%)  3
General disorders     
Chest discomfort  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Chills  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Death  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Drug withdrawal syndrome  1  1/220 (0.45%)  1 0/220 (0.00%)  0
General physical health deterioration  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Impaired healing  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Multi-organ failure  1  5/220 (2.27%)  5 7/220 (3.18%)  7
Necrosis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Pyrexia  1  2/220 (0.91%)  2 0/220 (0.00%)  0
Systemic inflammatory response syndrome  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Hepatobiliary disorders     
Cholecystitis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Cholecystitis acute  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Hepatic failure  1  1/220 (0.45%)  1 2/220 (0.91%)  2
Hepatosplenomegaly  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Immune system disorders     
Drug hypersensitivity  1  1/220 (0.45%)  2 0/220 (0.00%)  0
Infections and infestations     
Abdominal abscess  1  2/220 (0.91%)  3 2/220 (0.91%)  2
Abscess  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Bacteraemia  1  3/220 (1.36%)  3 0/220 (0.00%)  0
Bacterial sepsis  1  3/220 (1.36%)  3 4/220 (1.82%)  4
Candida endophthalmitis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Catheter related infection  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Cellulitis  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Cerebral aspergillosis  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Clostridium difficile colitis  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Device related infection  1  1/220 (0.45%)  2 0/220 (0.00%)  0
Diverticulitis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Enterobacter sepsis  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Escherichia urinary tract infection  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Fungal infection  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Infected skin ulcer  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Infection  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Klebsiella infection  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Klebsiella sepsis  1  2/220 (0.91%)  2 1/220 (0.45%)  1
Lung abscess  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Mediastinitis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Meningitis bacterial  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Neutropenic sepsis  1  2/220 (0.91%)  2 0/220 (0.00%)  0
Pneumonia  1  2/220 (0.91%)  2 6/220 (2.73%)  6
Pneumonia staphylococcal  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Postoperative wound infection  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Pseudomonal sepsis  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Sepsis  1  16/220 (7.27%)  16 9/220 (4.09%)  9
Septic shock  1  19/220 (8.64%)  19 11/220 (5.00%)  12
Staphylococcal sepsis  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Streptococcal bacteraemia  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Systemic candida  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Tracheobronchitis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Urinary tract infection bacterial  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Urinary tract infection enterococcal  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Urosepsis  1  0/220 (0.00%)  0 2/220 (0.91%)  2
Wound abscess  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Injury, poisoning and procedural complications     
Brain herniation  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Donor site complication  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Drug toxicity  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Facial bones fracture  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Fall  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Post procedural haemorrhage  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Soft tissue injury  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Subcutaneous haematoma  1  1/220 (0.45%)  2 0/220 (0.00%)  0
Transfusion reaction  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Wound dehiscence  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Wound haemorrhage  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Investigations     
Blood bilirubin increased  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Blood creatinine increased  1  1/220 (0.45%)  1 0/220 (0.00%)  0
C-reactive protein increased  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Hepatic enzyme abnormal  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Hepatic enzyme increased  1  2/220 (0.91%)  2 2/220 (0.91%)  2
Liver function test abnormal  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Oxygen saturation decreased  1  3/220 (1.36%)  3 0/220 (0.00%)  0
Metabolism and nutrition disorders     
Diabetic complication  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Diabetic ketoacidosis  1  1/220 (0.45%)  2 0/220 (0.00%)  0
Fluid overload  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Hypernatraemia  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Hypocalcaemia  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Hypoglycaemia  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Hypokalaemia  1  2/220 (0.91%)  2 3/220 (1.36%)  3
Hypomagnesaemia  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Hyponatraemia  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Lactic acidosis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Metabolic acidosis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Tumour lysis syndrome  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Fistula  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Systemic lupus erythematosus  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia recurrent  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Breast cancer  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Hodgkin's disease refractory  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Lung neoplasm malignant  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Lymphoma  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Malignant neoplasm progression  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Metastases to liver  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Metastases to meninges  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Neoplasm progression  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Non-Hodgkin's lymphoma  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Pancreatic carcinoma  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Sarcoma  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Thyroid neoplasm  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Nervous system disorders     
Basilar artery thrombosis  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Cerebral haemorrhage  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Cerebrovascular accident  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Convulsion  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Depressed level of consciousness  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Grand mal convulsion  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Headache  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Hypoglycaemic encephalopathy  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Hypoxic encephalopathy  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Intracranial haematoma  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Partial seizures  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Somnolence  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Status epilepticus  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Vasogenic cerebral oedema  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Renal and urinary disorders     
Nephrectasia  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Obstructive uropathy  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Renal failure  1  2/220 (0.91%)  2 2/220 (0.91%)  2
Renal failure acute  1  10/220 (4.55%)  10 3/220 (1.36%)  3
Renal failure chronic  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Urinary retention  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  2/220 (0.91%)  2 0/220 (0.00%)  0
Acute respiratory distress syndrome  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Acute respiratory failure  1  2/220 (0.91%)  2 1/220 (0.45%)  1
Aspiration  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Atelectasis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Dyspnoea  1  2/220 (0.91%)  2 1/220 (0.45%)  1
Pneumonia aspiration  1  3/220 (1.36%)  3 2/220 (0.91%)  2
Pulmonary alveolar haemorrhage  1  1/220 (0.45%)  1 1/220 (0.45%)  1
Pulmonary embolism  1  4/220 (1.82%)  4 2/220 (0.91%)  2
Pulmonary haemorrhage  1  2/220 (0.91%)  2 0/220 (0.00%)  0
Pulmonary necrosis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Respiratory distress  1  5/220 (2.27%)  5 1/220 (0.45%)  1
Respiratory failure  1  12/220 (5.45%)  13 8/220 (3.64%)  8
Skin and subcutaneous tissue disorders     
Stevens-Johnson syndrome  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Vascular disorders     
Arterial thrombosis limb  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Arteriosclerosis  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Deep vein thrombosis  1  2/220 (0.91%)  2 1/220 (0.45%)  1
Haematoma  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Haemodynamic instability  1  0/220 (0.00%)  0 1/220 (0.45%)  1
Hypertension  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Hypotension  1  3/220 (1.36%)  3 1/220 (0.45%)  1
Hypovolaemic shock  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Jugular vein thrombosis  1  1/220 (0.45%)  1 0/220 (0.00%)  0
Shock  1  2/220 (0.91%)  2 0/220 (0.00%)  0
Shock haemorrhagic  1  2/220 (0.91%)  2 0/220 (0.00%)  0
1
Term from vocabulary, MedDRA 12.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   162/220 (73.64%)      167/220 (75.91%)    
Blood and lymphatic system disorders     
Anaemia  1  13/220 (5.91%)  14 18/220 (8.18%)  21
Cardiac disorders     
Tachycardia  1  18/220 (8.18%)  20 9/220 (4.09%)  10
Gastrointestinal disorders     
Abdominal pain  1  16/220 (7.27%)  17 20/220 (9.09%)  23
Constipation  1  32/220 (14.55%)  34 24/220 (10.91%)  31
Diarrhoea  1  33/220 (15.00%)  37 41/220 (18.64%)  49
Nausea  1  21/220 (9.55%)  28 30/220 (13.64%)  37
Vomiting  1  33/220 (15.00%)  44 37/220 (16.82%)  49
General disorders     
Chills  1  11/220 (5.00%)  15 6/220 (2.73%)  6
Oedema peripheral  1  15/220 (6.82%)  17 16/220 (7.27%)  17
Pyrexia  1  38/220 (17.27%)  56 41/220 (18.64%)  73
Infections and infestations     
Bacteraemia  1  11/220 (5.00%)  12 9/220 (4.09%)  9
Staphylococcal bacteraemia  1  13/220 (5.91%)  13 9/220 (4.09%)  10
Urinary tract infection bacterial  1  7/220 (3.18%)  7 12/220 (5.45%)  12
Investigations     
Blood alkaline phosphatase increased  1  4/220 (1.82%)  4 11/220 (5.00%)  12
Gamma-glutamyltransferase increased  1  5/220 (2.27%)  5 11/220 (5.00%)  11
Metabolism and nutrition disorders     
Hyperkalaemia  1  18/220 (8.18%)  19 18/220 (8.18%)  21
Hypokalaemia  1  41/220 (18.64%)  49 44/220 (20.00%)  50
Hypomagnesaemia  1  18/220 (8.18%)  22 29/220 (13.18%)  31
Hyponatraemia  1  12/220 (5.45%)  12 14/220 (6.36%)  16
Hypophosphataemia  1  15/220 (6.82%)  15 9/220 (4.09%)  11
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  13/220 (5.91%)  15 6/220 (2.73%)  6
Psychiatric disorders     
Agitation  1  5/220 (2.27%)  5 13/220 (5.91%)  15
Anxiety  1  11/220 (5.00%)  11 7/220 (3.18%)  8
Insomnia  1  12/220 (5.45%)  13 10/220 (4.55%)  10
Respiratory, thoracic and mediastinal disorders     
Cough  1  10/220 (4.55%)  11 13/220 (5.91%)  14
Dyspnoea  1  15/220 (6.82%)  18 14/220 (6.36%)  14
Pleural effusion  1  11/220 (5.00%)  11 12/220 (5.45%)  12
Skin and subcutaneous tissue disorders     
Decubitus ulcer  1  14/220 (6.36%)  15 10/220 (4.55%)  19
Vascular disorders     
Hypertension  1  9/220 (4.09%)  9 12/220 (5.45%)  13
Hypotension  1  22/220 (10.00%)  30 27/220 (12.27%)  29
Phlebitis  1  14/220 (6.36%)  14 15/220 (6.82%)  20
1
Term from vocabulary, MedDRA 12.1
Indicates events were collected by systematic assessment
Enrollment in the clinical study was suspended in January 2009 pending further characterization of newly identified impurities. After successful completion of the studies, regulatory notifications and transfer of sponsorship from Basilea to Astellas,
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.
The results of this study may be published or presented at scientific meetings. If this is foreseen, the investigator agrees to submit all manuscripts or abstracts to the Sponsor at least 1 month prior to the submission of any such information to an editorial board or scientific review committee. This allows the Sponsor to protect proprietary information and to provide comments based on information from other studies that may not yet be available to the investigator.
Results Point of Contact
Name/Title: Clinical Trial Disclosure
Organization: Astellas Pharma Global Development, Inc.
Phone: 800-888-7704 ext 5473
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00413218     History of Changes
Obsolete Identifiers: NCT00444366
Other Study ID Numbers: 9766-CL-0105
WSA-CS-008 ( Other Identifier: Basilea Pharmaceutica Ltd )
2006-003951-18 ( EudraCT Number )
First Submitted: December 18, 2006
First Posted: December 19, 2006
Results First Submitted: July 5, 2017
Results First Posted: August 1, 2017
Last Update Posted: February 15, 2019