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

Sponsor
Astellas Pharma Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT00413218
Collaborator
Basilea Pharmaceutica (Industry)
450
113
2
95.8
4
0

Study Details

Study Description

Brief Summary

The purpose of the study is to compare the safety and efficacy of isavuconazole versus caspofungin followed by voriconazole in the treatment of candidemia and other invasive Candida infections.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Candida infections, representing approximately 80% of all major systemic fungal infections, are the fourth most common cause of nosocomial bloodstream infections, with a mortality rate of 40%. Isavuconazole is not yet approved for the treatment of fungal infections. This study investigates the efficacy and safety of intravenous and oral isavuconazole. Patients are randomized to isavuconazole and the reference regimen. Patients with a positive blood- or deep tissue culture of candida fungi can be included.

Study Design

Study Type:
Interventional
Actual Enrollment :
450 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase III, Double-blind, Randomized Study to Evaluate the Safety and Efficacy of BAL8557 Versus a Caspofungin Followed by Voriconazole Regimen in the Treatment of Candidemia and Other Invasive Candida Infections
Actual Study Start Date :
Mar 8, 2007
Actual Primary Completion Date :
Mar 3, 2015
Actual Study Completion Date :
Mar 3, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Isavuconazole (ISA)

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.

Drug: Isavuconazole
Administered by intravenous infusion.
Other Names:
  • ASP9766
  • BAL8557
  • Active Comparator: Caspofungin (CAS)/Voriconazole

    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. 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.

    Drug: Caspofungin
    Administered by intravenous infusion.
    Other Names:
  • Cancidas
  • Drug: Voriconazole
    Administered by intravenous infusion.
    Other Names:
  • VFend
  • Outcome Measures

    Primary Outcome Measures

    1. 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 [End of Intravenous Treatment (EOIV) (Days 11-56)]

      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.

    Secondary Outcome Measures

    1. 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) [End of Treatment (EOT) (Day 56) and FU1 (2 weeks after end of treatment)]

      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.

    2. 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 [EOT (Day 56) and FU2 (6 weeks after end of treatment)]

      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).

    3. Percentage of Participants With Clinical Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC) [EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment)]

      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).

    4. Percentage of Participants With Mycological Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC) [EOIV (Days 11-56), EOT (Day 56), FU1 (2 weeks after end of treatment) and FU2 (6 weeks after end of treatment)]

      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).

    5. Percentage of Participants With Mycological Response of Success at Day 7 and EOT as Determined by The Investigator [Day 7 and EOT (Day 56)]

      Success was defined as mycological response (eradication or presumed eradication).

    6. Percentage of Participants With Clinical Response of Success at Day 7 and EOT as Determined by The Investigator [Day 7 and EOT (Day 56)]

      Investigators defined clinical response as success if participants exhibited complete or partial clinical response after evaluation of clinical signs and symptoms.

    7. All-Cause Mortality (ACM) at Day 14 and Day 56 [Day 14 and Day 56]

      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.

    8. Time to First Confirmed Negative Culture [Day 1 up to FU1 (2 weeks after EOT (Day 56))]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients with candidemia or with an invasive Candida infection

    • Presence of fever, hypothermia or other appropriate local sign of infection

    • Female patients must be non-lactating and at no risk of pregnancy

    Exclusion Criteria:
    • Patients with a sole diagnosis of mucocutaneous candidiasis, i.e. oropharyngeal, esophageal or genital candidiasis; or candidal lower urinary tract infection or Candida isolated solely from respiratory tract specimens

    • Patients with candidemia who failed a previous antifungal therapy for the same infection

    • Patients previously enrolled in a phase III study with isavuconazole

    • Patients with a body weight <40kg

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294-0006
    2 Somero Research Corporation Palm Desert California United States 92211
    3 University of California Davis Health System Sacramento California United States 95817
    4 University of California at San Francisco San Francisco California United States 94143
    5 Idaho Falls Infectious Diseases PLLC Idaho Falls Idaho United States 83404
    6 Loyola University Hospital Maywood Illinois United States 60153
    7 Springfield Clinic LLP Springfield Illinois United States 62701
    8 Infectious Disease of Indiana Indianapolis Indiana United States 46280
    9 Ochsner Clinic Foundation New Orleans Louisiana United States 70121
    10 University of Maryland School of Medicine Baltimore Maryland United States 21201
    11 UMASS Memorial Medical Center Worcester Massachusetts United States 01655
    12 Henry Ford Hospital Detroit Michigan United States 48202
    13 Mercury Street Medical Group Butte Montana United States 59701
    14 Jersey Shore University Medical Center Neptune New Jersey United States 07753
    15 New York Presbyterian Hospital New York New York United States 10065
    16 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    17 Regional Infection Diseases Infusion Center Inc. Lima Ohio United States 45801
    18 Temple University Health Sciences Philadelphia Pennsylvania United States 19140
    19 Hospital Britanico de Buenos Aires Capital Federal Argentina C1280AEB
    20 Hospital General de Agudos Dr. Carlos G. Durand Capital Federal Argentina C1405DCS
    21 Hospital Italiano de Buenos Aires Ciudad Autonoma Argentina 1181
    22 Instituto Medico Especializado Alexander Fleming Ciudad Autonoma Argentina 1426
    23 Hospital General de Agudos Dr. Cosme Argerich La Boca Argentina 1157
    24 Fremantle Hospital Fremantle Australia 6160
    25 Mater Adult Hospital South Brisbane Australia
    26 Westmead Hospital Westmead Australia
    27 Princess Alexandra Hospital Woolloongabba Australia 4102
    28 Institut Jules Bordet Brussels Belgium 1000
    29 Universitair Ziekenhuis Brussel Brussels Belgium 1090
    30 ULB Hôpital Erasme Bruxelles Belgium 1070
    31 Universitair Ziekenhuis Gent Gent Belgium 9000
    32 Universitaire Ziekenhuizen Leuven Leuven Belgium 3000
    33 Hospital Felicio Rocho Belo Horizonte Brazil 30110-908
    34 Hospital das Clinicas da Universidade Federal de Minas Gerai Belo Horizonte Brazil 30130-100
    35 Santa Casa de Misericordia de Belo Horizonte Belo Horizonte Brazil 30150-221
    36 Hospital das Clinicas da UFPR Curitiba Brazil 80060-150
    37 Hospital Nossa Senhora das Gracas Curitiba Brazil 80810-040
    38 Hospital Sao Lucas - PUCRS Porto Alegre Brazil 90610-000
    39 Irmandade da Santa Casa de Misericordia de Porto Alegre Porto Alegre Brazil
    40 Hospital Universitario Clementino Fraga Filho Rio de Janeiro Brazil 21941-913
    41 Hospital Universitario de Santa Maria Santa Maria Brazil 97105-900
    42 Universidade Federal de Sao Paulo - UNIFESP São Paulo Brazil 04020-002
    43 University of Alberta Hospital Edmonton Alberta Canada T6G 2B7
    44 Hamilton Health Sciences - Henderson Site Hamilton Ontario Canada L8V 1C3
    45 Queen's University Kingston Ontario Canada K7L 3N6
    46 The Ottawa Hospital - General Campus Ottawa Ontario Canada K1H 8L6
    47 University Health Network - Toronto General Hospital Toronto Ontario Canada M5G 2N2
    48 Hôpital Maisonneuve - Rosemont Montreal Quebec Canada H1T 2M4
    49 Hospital Dr. Sotero del Rio Puente Alto Santiago Chile
    50 Hospital del Salvador Santiago Chile
    51 Hospital Dr. Hernan Henriquez Aravena Temuco Chile 4780000
    52 West China Hospital of Sichuan University Chengdu China 610041
    53 Huashan Hospital Fudan University Shanghai China 200040
    54 Hôpital Hautepierre Strasbourg France 67048
    55 Hôpital de Brabois Adultes Vandoeuvre les Nancy France 54511
    56 Charite Campus Mitte Berlin Germany 10117
    57 Universitaetsklinikum Freiburg Freiburg Germany
    58 Universitaet Koeln Koeln Germany 50937
    59 Klinikum St. Georg Leipzig Germany 04129
    60 Universitaetsklinik Leipzig Leipzig Germany 04289
    61 Universitaetsklinikum Leipzig Luebeck Germany
    62 Universitaetsklinikum Wuerzburg Wuerzburg Germany 97080
    63 Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum Debrecen Hungary 4032
    64 Petz Aladar Megyei Oktato Korhaz Györ Hungary 9024
    65 Max Super Speciality Hospital New Delhi Delhi India 110017
    66 Metro Centre for Respiratory Diseases Noida Delhi India 201301
    67 Kasturba Medical College and Hospital Mangalore Karna India 575001
    68 Kasturba Medical College K. M. C. Hospital Manipal Karna India 576104
    69 Amrita Institute Of Medical Science Cochin Kerala India 682041
    70 Deenanath Mangeshkar Hospital and Research Centre Pune Mahara India 411004
    71 Apollo Hospitals Educational & Research Foundation Chennai India
    72 Nizam's Institute of Medical Sciences Hyderabad India 500082
    73 AMRI Hospital Kolkata India 700098
    74 Christian Medical College & Hospital Vellore Tamilnadu India
    75 Ha Emek Medical Center Afula Israel 18101
    76 Rambam Health Care Campus Haifa Israel 31096
    77 Wolfson Medical Center Holon Israel 58100
    78 Hadassah Universtiy Hospital - Ein Kerem Jerusalem Israel 91200
    79 Sapir Medical Center, Meir Hospital Kfar-Saba Israel 44281
    80 Rabin MC Petah Israel 49100
    81 Chaim Sheba Medical Center Ramat Gan Israel 52621
    82 Sourasky MC Ichilov Hospital Tel Aviv Tel Aviv Israel 64239
    83 Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Ma Bologna Italy 40138
    84 Azienda Ospedaliera Spedali Civili di Brescia Brescia Italy 25126
    85 Ente Ospedaliero Ospedeli Galliera Genova Italy 16128
    86 Azienda Ospedaliero Universitaria San Martino Genova Italy 16132
    87 Azienda Ospedaliera di Verona-Ospedale Civile Maggiore Verona Italy 37134
    88 AUB Medical Center Beirut Lebanon 11-0236
    89 Rafik Hariri Uni Hospital Beirut Lebanon 5244
    90 Hospital Ampang Ampang Malaysia 68000
    91 Pusat Perubatan Universiti Kebangsaan Malaysia Kuala Lumpur Malaysia 56000
    92 Hospital Civil de Guadalajara Fray Antonio Alcalde Guadalajara Mexico 44280
    93 Hospital Civil de Guadalajara Dr Juan I Menchaca Guadalajara Mexico 44340
    94 Instituto Nacional de Ciencias Medicas y Nutricion Salvador Mexico Mexico 14000
    95 Hospital Universitario Dr Jose Eleuterio Gonzalez Monterrey Mexico 64460
    96 Auckland City Hospital Auckland New Zealand
    97 Waikato Urology Research Ltd Hamilton New Zealand
    98 De La Salle Health Sciences Institute- DLSUMC Cavite City Philippines
    99 Philippine General Hospital Manila Philippines
    100 S.I. Russian Oncological Research Center n.a. N.N. Blokhin Moscow Russian Federation 115478
    101 State Institution "Hematology Research Center" RAMS Moscow Russian Federation 125167
    102 Singapore General Hospital - Parent Singapore Singapore 169608
    103 National Neuroscience Institute Singapore Singapore 308433
    104 Unitas Hospital Lyttelton Centurion South Africa 0157
    105 Hospital del Mar Barcelona Spain 08003
    106 Hôpitaux Universitaires de Genève - HUG Geneva Switzerland
    107 Universitaetsspital Zuerich Zurich Switzerland
    108 Siriraj Hospital Bangkoknoi Thailand 10700
    109 Songklanagarind Hospital Hat Yai Thailand 90110
    110 Maharat Nakhon Ratchasima Hospital Muang Thailand 30000
    111 Srinagarind Hospital Muang Thailand 40002
    112 Maharaj Nakorn Chiang Mai Hospital Muang Thailand 50200
    113 Ramathibodi Hospital Ratchathewi Thailand 10400

    Sponsors and Collaborators

    • Astellas Pharma Inc
    • Basilea Pharmaceutica

    Investigators

    • Study Director: Medical Director, Astellas Pharma Global Development

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Astellas Pharma Inc
    ClinicalTrials.gov Identifier:
    NCT00413218
    Other Study ID Numbers:
    • 9766-CL-0105
    • WSA-CS-008
    • 2006-003951-18
    • NCT00444366
    First Posted:
    Dec 19, 2006
    Last Update Posted:
    Feb 15, 2019
    Last Verified:
    Jan 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Astellas Pharma Inc
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    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 Detail Participants were stratified at randomization by geographical region and baseline neutropenic status.
    Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
    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 223 227
    Intent to Treat Population (ITT) 221 219
    COMPLETED 120 131
    NOT COMPLETED 103 96

    Baseline Characteristics

    Arm/Group Title Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole Total
    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 Participants 221 219 440
    Age (Years) [Geometric Mean (Standard Deviation) ]
    Geometric Mean (Standard Deviation) [Years]
    58.0
    (17.54)
    57.9
    (16.88)
    58.0
    (17.20)
    Sex: Female, Male (Count of Participants)
    Female
    78
    35.3%
    93
    42.5%
    171
    38.9%
    Male
    143
    64.7%
    126
    57.5%
    269
    61.1%
    Race/Ethnicity, Customized (Count of Participants)
    White
    150
    67.9%
    144
    65.8%
    294
    66.8%
    Black or African American
    11
    5%
    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 (Count of Participants)
    Hispanic or Latino
    26
    11.8%
    19
    8.7%
    45
    10.2%
    Not Hispanic or Latino
    187
    84.6%
    195
    89%
    382
    86.8%
    Missing
    8
    3.6%
    5
    2.3%
    13
    3%
    Neutropenic Status: Presence or Absence of Neutropenia (Count of Participants)
    Presence
    25
    11.3%
    24
    11%
    49
    11.1%
    Absence
    196
    88.7%
    195
    89%
    391
    88.9%
    Geographical Region (Count of Participants)
    North America
    38
    17.2%
    33
    15.1%
    71
    16.1%
    Western Europe
    54
    24.4%
    56
    25.6%
    110
    25%
    Other Regions
    129
    58.4%
    130
    59.4%
    259
    58.9%

    Outcome Measures

    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
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 199 201
    Number [Percentage of Participants]
    60.3
    27.3%
    71.1
    32.5%
    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.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -10.8
    Confidence Interval (2-Sided) 95%
    -19.9 to -1.8
    Parameter Dispersion Type:
    Value:
    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)
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 199 201
    Number [Percentage of Participants]
    54.8
    24.8%
    57.2
    26.1%
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -2.7
    Confidence Interval (2-Sided) 95%
    -12.2 to 6.8
    Parameter Dispersion Type:
    Value:
    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
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 199 201
    EOT (Day 56)
    61.3
    27.7%
    72.1
    32.9%
    FU2 (6 weeks after end of treatment)
    43.2
    19.5%
    48.3
    22.1%
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference %
    Estimated Value -10.9
    Confidence Interval (2-Sided) 95%
    -19.9 to -1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference %
    Estimated Value -5.4
    Confidence Interval (2-Sided) 95%
    -15.00 to 4.2
    Parameter Dispersion Type:
    Value:
    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)
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 199 201
    Success- End of Intravenous Treatment (EOIV)
    76.4
    34.6%
    84.1
    38.4%
    Success- End of Treatment (EOT)
    76.4
    34.6%
    84.6
    38.6%
    Success- Follow-up Visit 1 (FU1)
    67.8
    30.7%
    67.7
    30.9%
    Success- Follow-up Visit 2 (FU2)
    52.8
    23.9%
    58.2
    26.6%
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -8.2
    Confidence Interval (2-Sided) 95%
    -15.4 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -8.6
    Confidence Interval (2-Sided) 95%
    -15.8 to -1.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -9.1 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -5.8
    Confidence Interval (2-Sided) 95%
    -15.3 to 3.6
    Parameter Dispersion Type:
    Value:
    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)
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 199 201
    Success-EOIV
    70.9
    32.1%
    85.6
    39.1%
    Success-EOT
    71.9
    32.5%
    87.6
    40%
    Success-FU1
    66.8
    30.2%
    65.7
    30%
    Success-FU2
    51.8
    23.4%
    56.7
    25.9%
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -14.9
    Confidence Interval (2-Sided) 95%
    -22.7 to -7.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -15.9
    Confidence Interval (2-Sided) 95%
    -23.5 to -8.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -0.7
    Confidence Interval (2-Sided) 95%
    -8.1 to 9.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -5.2
    Confidence Interval (2-Sided) 95%
    -14.7 to 4.3
    Parameter Dispersion Type:
    Value:
    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
    Description Success was defined as mycological response (eradication or presumed eradication).
    Time Frame Day 7 and EOT (Day 56)

    Outcome Measure Data

    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
    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.
    Measure Participants 199 201
    Day 7
    61.3
    27.7%
    72.1
    32.9%
    EOT
    72.9
    33%
    81.1
    37%
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -11.4
    Confidence Interval (2-Sided) 95%
    -20.4 to -2.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -8.5
    Confidence Interval (2-Sided) 95%
    -16.5 to -0.4
    Parameter Dispersion Type:
    Value:
    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
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 199 201
    Day 7
    54.3
    24.6%
    64.7
    29.5%
    EOT
    70.9
    32.1%
    78.6
    35.9%
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -11.1
    Confidence Interval (2-Sided) 95%
    -20.3 to -1.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments The 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value -8.1
    Confidence Interval (2-Sided) 95%
    -16.3 to 0.1
    Parameter Dispersion Type:
    Value:
    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
    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

    Outcome Measure Data

    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
    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.
    Measure Participants 199 201
    Day 14 All-cause Mortality
    14.6
    6.6%
    12.4
    5.7%
    Day 56 All-cause Mortality
    30.7
    13.9%
    29.9
    13.7%
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value 2.5
    Confidence Interval (2-Sided) 95%
    -3.8 to 8.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Adjusted Treatment Difference (%)
    Estimated Value 1.4
    Confidence Interval (2-Sided) 95%
    -7.1 to 10.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Time to First Confirmed Negative Culture
    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))

    Outcome Measure Data

    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
    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.
    Measure Participants 120 119
    Median (95% Confidence Interval) [Days]
    4.0
    3.0

    Adverse Events

    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
    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 (%) # Events Affected / at Risk (%) # Events
    Total 55/220 (25%) 55/220 (25%)
    Serious Adverse Events
    Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 112/220 (50.9%) 106/220 (48.2%)
    Blood and lymphatic system disorders
    Anaemia 1/220 (0.5%) 1 3/220 (1.4%) 3
    Anaemia haemolytic autoimmune 0/220 (0%) 0 1/220 (0.5%) 1
    Coagulopathy 1/220 (0.5%) 1 0/220 (0%) 0
    Disseminated intravascular coagulation 0/220 (0%) 0 1/220 (0.5%) 1
    Neutropenia 1/220 (0.5%) 1 2/220 (0.9%) 2
    Pancytopenia 1/220 (0.5%) 1 0/220 (0%) 0
    Thrombocytopenia 1/220 (0.5%) 1 0/220 (0%) 0
    Cardiac disorders
    Arrhythmia 1/220 (0.5%) 1 0/220 (0%) 0
    Atrial fibrillation 0/220 (0%) 0 1/220 (0.5%) 1
    Bradycardia 1/220 (0.5%) 1 0/220 (0%) 0
    Cardiac arrest 4/220 (1.8%) 6 6/220 (2.7%) 6
    Cardiac failure 0/220 (0%) 0 2/220 (0.9%) 2
    Cardio-respiratory arrest 1/220 (0.5%) 1 1/220 (0.5%) 1
    Cardiomyopathy 0/220 (0%) 0 1/220 (0.5%) 1
    Coronary artery stenosis 0/220 (0%) 0 1/220 (0.5%) 1
    Hypertensive heart disease 0/220 (0%) 0 1/220 (0.5%) 1
    Myocardial infarction 1/220 (0.5%) 1 1/220 (0.5%) 1
    Pericardial effusion 0/220 (0%) 0 1/220 (0.5%) 1
    Sick sinus syndrome 0/220 (0%) 0 1/220 (0.5%) 1
    Tachycardia 1/220 (0.5%) 1 0/220 (0%) 0
    Torsade de pointes 1/220 (0.5%) 1 0/220 (0%) 0
    Ventricular extrasystoles 1/220 (0.5%) 1 0/220 (0%) 0
    Ventricular fibrillation 1/220 (0.5%) 1 0/220 (0%) 0
    Ventricular tachycardia 2/220 (0.9%) 2 0/220 (0%) 0
    Congenital, familial and genetic disorders
    Sickle cell anaemia with crisis 1/220 (0.5%) 1 0/220 (0%) 0
    Endocrine disorders
    Diabetes insipidus 0/220 (0%) 0 1/220 (0.5%) 1
    Eye disorders
    Vision blurred 1/220 (0.5%) 1 0/220 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 0/220 (0%) 0 1/220 (0.5%) 1
    Abdominal pain 0/220 (0%) 0 2/220 (0.9%) 3
    Ascites 0/220 (0%) 0 1/220 (0.5%) 1
    Diarrhoea 2/220 (0.9%) 2 0/220 (0%) 0
    Duodenal perforation 0/220 (0%) 0 1/220 (0.5%) 1
    Enterocutaneous fistula 0/220 (0%) 0 1/220 (0.5%) 1
    Faecaloma 1/220 (0.5%) 1 0/220 (0%) 0
    Gastrointestinal haemorrhage 1/220 (0.5%) 1 1/220 (0.5%) 1
    Intestinal obstruction 1/220 (0.5%) 1 0/220 (0%) 0
    Intestinal perforation 1/220 (0.5%) 1 0/220 (0%) 0
    Lower gastrointestinal haemorrhage 0/220 (0%) 0 1/220 (0.5%) 1
    Melaena 1/220 (0.5%) 1 0/220 (0%) 0
    Nausea 1/220 (0.5%) 1 2/220 (0.9%) 2
    Pancreatitis 1/220 (0.5%) 1 1/220 (0.5%) 1
    Peritonitis 1/220 (0.5%) 1 1/220 (0.5%) 1
    Proctalgia 0/220 (0%) 0 1/220 (0.5%) 1
    Rectal haemorrhage 0/220 (0%) 0 1/220 (0.5%) 2
    Upper gastrointestinal haemorrhage 1/220 (0.5%) 1 1/220 (0.5%) 1
    Vomiting 1/220 (0.5%) 1 3/220 (1.4%) 3
    General disorders
    Chest discomfort 1/220 (0.5%) 1 0/220 (0%) 0
    Chills 0/220 (0%) 0 1/220 (0.5%) 1
    Death 0/220 (0%) 0 1/220 (0.5%) 1
    Drug withdrawal syndrome 1/220 (0.5%) 1 0/220 (0%) 0
    General physical health deterioration 0/220 (0%) 0 1/220 (0.5%) 1
    Impaired healing 1/220 (0.5%) 1 0/220 (0%) 0
    Multi-organ failure 5/220 (2.3%) 5 7/220 (3.2%) 7
    Necrosis 1/220 (0.5%) 1 0/220 (0%) 0
    Pyrexia 2/220 (0.9%) 2 0/220 (0%) 0
    Systemic inflammatory response syndrome 0/220 (0%) 0 1/220 (0.5%) 1
    Hepatobiliary disorders
    Cholecystitis 1/220 (0.5%) 1 0/220 (0%) 0
    Cholecystitis acute 0/220 (0%) 0 1/220 (0.5%) 1
    Hepatic failure 1/220 (0.5%) 1 2/220 (0.9%) 2
    Hepatosplenomegaly 0/220 (0%) 0 1/220 (0.5%) 1
    Immune system disorders
    Drug hypersensitivity 1/220 (0.5%) 2 0/220 (0%) 0
    Infections and infestations
    Abdominal abscess 2/220 (0.9%) 3 2/220 (0.9%) 2
    Abscess 0/220 (0%) 0 1/220 (0.5%) 1
    Bacteraemia 3/220 (1.4%) 3 0/220 (0%) 0
    Bacterial sepsis 3/220 (1.4%) 3 4/220 (1.8%) 4
    Candida endophthalmitis 1/220 (0.5%) 1 0/220 (0%) 0
    Catheter related infection 0/220 (0%) 0 1/220 (0.5%) 1
    Cellulitis 0/220 (0%) 0 1/220 (0.5%) 1
    Cerebral aspergillosis 0/220 (0%) 0 1/220 (0.5%) 1
    Clostridium difficile colitis 1/220 (0.5%) 1 1/220 (0.5%) 1
    Device related infection 1/220 (0.5%) 2 0/220 (0%) 0
    Diverticulitis 1/220 (0.5%) 1 0/220 (0%) 0
    Enterobacter sepsis 0/220 (0%) 0 1/220 (0.5%) 1
    Escherichia urinary tract infection 1/220 (0.5%) 1 0/220 (0%) 0
    Fungal infection 0/220 (0%) 0 1/220 (0.5%) 1
    Infected skin ulcer 1/220 (0.5%) 1 0/220 (0%) 0
    Infection 1/220 (0.5%) 1 0/220 (0%) 0
    Klebsiella infection 0/220 (0%) 0 1/220 (0.5%) 1
    Klebsiella sepsis 2/220 (0.9%) 2 1/220 (0.5%) 1
    Lung abscess 1/220 (0.5%) 1 0/220 (0%) 0
    Mediastinitis 1/220 (0.5%) 1 0/220 (0%) 0
    Meningitis bacterial 1/220 (0.5%) 1 0/220 (0%) 0
    Neutropenic sepsis 2/220 (0.9%) 2 0/220 (0%) 0
    Pneumonia 2/220 (0.9%) 2 6/220 (2.7%) 6
    Pneumonia staphylococcal 0/220 (0%) 0 1/220 (0.5%) 1
    Postoperative wound infection 1/220 (0.5%) 1 0/220 (0%) 0
    Pseudomonal sepsis 0/220 (0%) 0 1/220 (0.5%) 1
    Sepsis 16/220 (7.3%) 16 9/220 (4.1%) 9
    Septic shock 19/220 (8.6%) 19 11/220 (5%) 12
    Staphylococcal sepsis 0/220 (0%) 0 1/220 (0.5%) 1
    Streptococcal bacteraemia 1/220 (0.5%) 1 0/220 (0%) 0
    Systemic candida 1/220 (0.5%) 1 1/220 (0.5%) 1
    Tracheobronchitis 1/220 (0.5%) 1 0/220 (0%) 0
    Urinary tract infection bacterial 0/220 (0%) 0 1/220 (0.5%) 1
    Urinary tract infection enterococcal 0/220 (0%) 0 1/220 (0.5%) 1
    Urosepsis 0/220 (0%) 0 2/220 (0.9%) 2
    Wound abscess 1/220 (0.5%) 1 0/220 (0%) 0
    Injury, poisoning and procedural complications
    Brain herniation 1/220 (0.5%) 1 0/220 (0%) 0
    Donor site complication 0/220 (0%) 0 1/220 (0.5%) 1
    Drug toxicity 0/220 (0%) 0 1/220 (0.5%) 1
    Facial bones fracture 0/220 (0%) 0 1/220 (0.5%) 1
    Fall 0/220 (0%) 0 1/220 (0.5%) 1
    Post procedural haemorrhage 0/220 (0%) 0 1/220 (0.5%) 1
    Soft tissue injury 1/220 (0.5%) 1 0/220 (0%) 0
    Subcutaneous haematoma 1/220 (0.5%) 2 0/220 (0%) 0
    Transfusion reaction 1/220 (0.5%) 1 0/220 (0%) 0
    Wound dehiscence 0/220 (0%) 0 1/220 (0.5%) 1
    Wound haemorrhage 0/220 (0%) 0 1/220 (0.5%) 1
    Investigations
    Blood bilirubin increased 1/220 (0.5%) 1 0/220 (0%) 0
    Blood creatinine increased 1/220 (0.5%) 1 0/220 (0%) 0
    C-reactive protein increased 1/220 (0.5%) 1 0/220 (0%) 0
    Hepatic enzyme abnormal 0/220 (0%) 0 1/220 (0.5%) 1
    Hepatic enzyme increased 2/220 (0.9%) 2 2/220 (0.9%) 2
    Liver function test abnormal 1/220 (0.5%) 1 0/220 (0%) 0
    Oxygen saturation decreased 3/220 (1.4%) 3 0/220 (0%) 0
    Metabolism and nutrition disorders
    Diabetic complication 1/220 (0.5%) 1 0/220 (0%) 0
    Diabetic ketoacidosis 1/220 (0.5%) 2 0/220 (0%) 0
    Fluid overload 1/220 (0.5%) 1 0/220 (0%) 0
    Hypernatraemia 0/220 (0%) 0 1/220 (0.5%) 1
    Hypocalcaemia 1/220 (0.5%) 1 0/220 (0%) 0
    Hypoglycaemia 0/220 (0%) 0 1/220 (0.5%) 1
    Hypokalaemia 2/220 (0.9%) 2 3/220 (1.4%) 3
    Hypomagnesaemia 1/220 (0.5%) 1 0/220 (0%) 0
    Hyponatraemia 0/220 (0%) 0 1/220 (0.5%) 1
    Lactic acidosis 1/220 (0.5%) 1 0/220 (0%) 0
    Metabolic acidosis 1/220 (0.5%) 1 0/220 (0%) 0
    Tumour lysis syndrome 1/220 (0.5%) 1 0/220 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/220 (0.5%) 1 0/220 (0%) 0
    Fistula 1/220 (0.5%) 1 0/220 (0%) 0
    Systemic lupus erythematosus 0/220 (0%) 0 1/220 (0.5%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia recurrent 0/220 (0%) 0 1/220 (0.5%) 1
    Breast cancer 1/220 (0.5%) 1 0/220 (0%) 0
    Hodgkin's disease refractory 1/220 (0.5%) 1 0/220 (0%) 0
    Lung neoplasm malignant 0/220 (0%) 0 1/220 (0.5%) 1
    Lymphoma 1/220 (0.5%) 1 1/220 (0.5%) 1
    Malignant neoplasm progression 1/220 (0.5%) 1 0/220 (0%) 0
    Metastases to liver 0/220 (0%) 0 1/220 (0.5%) 1
    Metastases to meninges 1/220 (0.5%) 1 0/220 (0%) 0
    Neoplasm progression 0/220 (0%) 0 1/220 (0.5%) 1
    Non-Hodgkin's lymphoma 0/220 (0%) 0 1/220 (0.5%) 1
    Pancreatic carcinoma 1/220 (0.5%) 1 0/220 (0%) 0
    Sarcoma 0/220 (0%) 0 1/220 (0.5%) 1
    Thyroid neoplasm 0/220 (0%) 0 1/220 (0.5%) 1
    Nervous system disorders
    Basilar artery thrombosis 0/220 (0%) 0 1/220 (0.5%) 1
    Cerebral haemorrhage 1/220 (0.5%) 1 1/220 (0.5%) 1
    Cerebrovascular accident 1/220 (0.5%) 1 0/220 (0%) 0
    Convulsion 1/220 (0.5%) 1 1/220 (0.5%) 1
    Depressed level of consciousness 1/220 (0.5%) 1 0/220 (0%) 0
    Grand mal convulsion 1/220 (0.5%) 1 1/220 (0.5%) 1
    Headache 1/220 (0.5%) 1 0/220 (0%) 0
    Hypoglycaemic encephalopathy 0/220 (0%) 0 1/220 (0.5%) 1
    Hypoxic encephalopathy 0/220 (0%) 0 1/220 (0.5%) 1
    Intracranial haematoma 1/220 (0.5%) 1 0/220 (0%) 0
    Partial seizures 0/220 (0%) 0 1/220 (0.5%) 1
    Somnolence 0/220 (0%) 0 1/220 (0.5%) 1
    Status epilepticus 0/220 (0%) 0 1/220 (0.5%) 1
    Vasogenic cerebral oedema 0/220 (0%) 0 1/220 (0.5%) 1
    Renal and urinary disorders
    Nephrectasia 0/220 (0%) 0 1/220 (0.5%) 1
    Obstructive uropathy 0/220 (0%) 0 1/220 (0.5%) 1
    Renal failure 2/220 (0.9%) 2 2/220 (0.9%) 2
    Renal failure acute 10/220 (4.5%) 10 3/220 (1.4%) 3
    Renal failure chronic 0/220 (0%) 0 1/220 (0.5%) 1
    Urinary retention 0/220 (0%) 0 1/220 (0.5%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 2/220 (0.9%) 2 0/220 (0%) 0
    Acute respiratory distress syndrome 0/220 (0%) 0 1/220 (0.5%) 1
    Acute respiratory failure 2/220 (0.9%) 2 1/220 (0.5%) 1
    Aspiration 1/220 (0.5%) 1 0/220 (0%) 0
    Atelectasis 1/220 (0.5%) 1 0/220 (0%) 0
    Dyspnoea 2/220 (0.9%) 2 1/220 (0.5%) 1
    Pneumonia aspiration 3/220 (1.4%) 3 2/220 (0.9%) 2
    Pulmonary alveolar haemorrhage 1/220 (0.5%) 1 1/220 (0.5%) 1
    Pulmonary embolism 4/220 (1.8%) 4 2/220 (0.9%) 2
    Pulmonary haemorrhage 2/220 (0.9%) 2 0/220 (0%) 0
    Pulmonary necrosis 1/220 (0.5%) 1 0/220 (0%) 0
    Respiratory distress 5/220 (2.3%) 5 1/220 (0.5%) 1
    Respiratory failure 12/220 (5.5%) 13 8/220 (3.6%) 8
    Skin and subcutaneous tissue disorders
    Stevens-Johnson syndrome 0/220 (0%) 0 1/220 (0.5%) 1
    Vascular disorders
    Arterial thrombosis limb 1/220 (0.5%) 1 0/220 (0%) 0
    Arteriosclerosis 0/220 (0%) 0 1/220 (0.5%) 1
    Deep vein thrombosis 2/220 (0.9%) 2 1/220 (0.5%) 1
    Haematoma 1/220 (0.5%) 1 0/220 (0%) 0
    Haemodynamic instability 0/220 (0%) 0 1/220 (0.5%) 1
    Hypertension 1/220 (0.5%) 1 0/220 (0%) 0
    Hypotension 3/220 (1.4%) 3 1/220 (0.5%) 1
    Hypovolaemic shock 1/220 (0.5%) 1 0/220 (0%) 0
    Jugular vein thrombosis 1/220 (0.5%) 1 0/220 (0%) 0
    Shock 2/220 (0.9%) 2 0/220 (0%) 0
    Shock haemorrhagic 2/220 (0.9%) 2 0/220 (0%) 0
    Other (Not Including Serious) Adverse Events
    Isavuconazole (ISA) Caspofungin (CAS)/Voriconazole
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 162/220 (73.6%) 167/220 (75.9%)
    Blood and lymphatic system disorders
    Anaemia 13/220 (5.9%) 14 18/220 (8.2%) 21
    Cardiac disorders
    Tachycardia 18/220 (8.2%) 20 9/220 (4.1%) 10
    Gastrointestinal disorders
    Abdominal pain 16/220 (7.3%) 17 20/220 (9.1%) 23
    Constipation 32/220 (14.5%) 34 24/220 (10.9%) 31
    Diarrhoea 33/220 (15%) 37 41/220 (18.6%) 49
    Nausea 21/220 (9.5%) 28 30/220 (13.6%) 37
    Vomiting 33/220 (15%) 44 37/220 (16.8%) 49
    General disorders
    Chills 11/220 (5%) 15 6/220 (2.7%) 6
    Oedema peripheral 15/220 (6.8%) 17 16/220 (7.3%) 17
    Pyrexia 38/220 (17.3%) 56 41/220 (18.6%) 73
    Infections and infestations
    Bacteraemia 11/220 (5%) 12 9/220 (4.1%) 9
    Staphylococcal bacteraemia 13/220 (5.9%) 13 9/220 (4.1%) 10
    Urinary tract infection bacterial 7/220 (3.2%) 7 12/220 (5.5%) 12
    Investigations
    Blood alkaline phosphatase increased 4/220 (1.8%) 4 11/220 (5%) 12
    Gamma-glutamyltransferase increased 5/220 (2.3%) 5 11/220 (5%) 11
    Metabolism and nutrition disorders
    Hyperkalaemia 18/220 (8.2%) 19 18/220 (8.2%) 21
    Hypokalaemia 41/220 (18.6%) 49 44/220 (20%) 50
    Hypomagnesaemia 18/220 (8.2%) 22 29/220 (13.2%) 31
    Hyponatraemia 12/220 (5.5%) 12 14/220 (6.4%) 16
    Hypophosphataemia 15/220 (6.8%) 15 9/220 (4.1%) 11
    Musculoskeletal and connective tissue disorders
    Pain in extremity 13/220 (5.9%) 15 6/220 (2.7%) 6
    Psychiatric disorders
    Agitation 5/220 (2.3%) 5 13/220 (5.9%) 15
    Anxiety 11/220 (5%) 11 7/220 (3.2%) 8
    Insomnia 12/220 (5.5%) 13 10/220 (4.5%) 10
    Respiratory, thoracic and mediastinal disorders
    Cough 10/220 (4.5%) 11 13/220 (5.9%) 14
    Dyspnoea 15/220 (6.8%) 18 14/220 (6.4%) 14
    Pleural effusion 11/220 (5%) 11 12/220 (5.5%) 12
    Skin and subcutaneous tissue disorders
    Decubitus ulcer 14/220 (6.4%) 15 10/220 (4.5%) 19
    Vascular disorders
    Hypertension 9/220 (4.1%) 9 12/220 (5.5%) 13
    Hypotension 22/220 (10%) 30 27/220 (12.3%) 29
    Phlebitis 14/220 (6.4%) 14 15/220 (6.8%) 20

    Limitations/Caveats

    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,

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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
    Email astellas.resultsdisclosure@astellas.com
    Responsible Party:
    Astellas Pharma Inc
    ClinicalTrials.gov Identifier:
    NCT00413218
    Other Study ID Numbers:
    • 9766-CL-0105
    • WSA-CS-008
    • 2006-003951-18
    • NCT00444366
    First Posted:
    Dec 19, 2006
    Last Update Posted:
    Feb 15, 2019
    Last Verified:
    Jan 1, 2019