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
Enrollment
113
Locations
2
Arms
95.8
Actual Duration (Months)
4
Patients Per Site
0
Patients Per Site Per Month

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.

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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1University of Alabama at BirminghamBirminghamAlabamaUnited States35294-0006
    2Somero Research CorporationPalm DesertCaliforniaUnited States92211
    3University of California Davis Health SystemSacramentoCaliforniaUnited States95817
    4University of California at San FranciscoSan FranciscoCaliforniaUnited States94143
    5Idaho Falls Infectious Diseases PLLCIdaho FallsIdahoUnited States83404
    6Loyola University HospitalMaywoodIllinoisUnited States60153
    7Springfield Clinic LLPSpringfieldIllinoisUnited States62701
    8Infectious Disease of IndianaIndianapolisIndianaUnited States46280
    9Ochsner Clinic FoundationNew OrleansLouisianaUnited States70121
    10University of Maryland School of MedicineBaltimoreMarylandUnited States21201
    11UMASS Memorial Medical CenterWorcesterMassachusettsUnited States01655
    12Henry Ford HospitalDetroitMichiganUnited States48202
    13Mercury Street Medical GroupButteMontanaUnited States59701
    14Jersey Shore University Medical CenterNeptuneNew JerseyUnited States07753
    15New York Presbyterian HospitalNew YorkNew YorkUnited States10065
    16Wake Forest University Health SciencesWinston-SalemNorth CarolinaUnited States27157
    17Regional Infection Diseases Infusion Center Inc.LimaOhioUnited States45801
    18Temple University Health SciencesPhiladelphiaPennsylvaniaUnited States19140
    19Hospital Britanico de Buenos AiresCapital FederalArgentinaC1280AEB
    20Hospital General de Agudos Dr. Carlos G. DurandCapital FederalArgentinaC1405DCS
    21Hospital Italiano de Buenos AiresCiudad AutonomaArgentina1181
    22Instituto Medico Especializado Alexander FlemingCiudad AutonomaArgentina1426
    23Hospital General de Agudos Dr. Cosme ArgerichLa BocaArgentina1157
    24Fremantle HospitalFremantleAustralia6160
    25Mater Adult HospitalSouth BrisbaneAustralia
    26Westmead HospitalWestmeadAustralia
    27Princess Alexandra HospitalWoolloongabbaAustralia4102
    28Institut Jules BordetBrusselsBelgium1000
    29Universitair Ziekenhuis BrusselBrusselsBelgium1090
    30ULB Hôpital ErasmeBruxellesBelgium1070
    31Universitair Ziekenhuis GentGentBelgium9000
    32Universitaire Ziekenhuizen LeuvenLeuvenBelgium3000
    33Hospital Felicio RochoBelo HorizonteBrazil30110-908
    34Hospital das Clinicas da Universidade Federal de Minas GeraiBelo HorizonteBrazil30130-100
    35Santa Casa de Misericordia de Belo HorizonteBelo HorizonteBrazil30150-221
    36Hospital das Clinicas da UFPRCuritibaBrazil80060-150
    37Hospital Nossa Senhora das GracasCuritibaBrazil80810-040
    38Hospital Sao Lucas - PUCRSPorto AlegreBrazil90610-000
    39Irmandade da Santa Casa de Misericordia de Porto AlegrePorto AlegreBrazil
    40Hospital Universitario Clementino Fraga FilhoRio de JaneiroBrazil21941-913
    41Hospital Universitario de Santa MariaSanta MariaBrazil97105-900
    42Universidade Federal de Sao Paulo - UNIFESPSão PauloBrazil04020-002
    43University of Alberta HospitalEdmontonAlbertaCanadaT6G 2B7
    44Hamilton Health Sciences - Henderson SiteHamiltonOntarioCanadaL8V 1C3
    45Queen's UniversityKingstonOntarioCanadaK7L 3N6
    46The Ottawa Hospital - General CampusOttawaOntarioCanadaK1H 8L6
    47University Health Network - Toronto General HospitalTorontoOntarioCanadaM5G 2N2
    48Hôpital Maisonneuve - RosemontMontrealQuebecCanadaH1T 2M4
    49Hospital Dr. Sotero del RioPuente Alto SantiagoChile
    50Hospital del SalvadorSantiagoChile
    51Hospital Dr. Hernan Henriquez AravenaTemucoChile4780000
    52West China Hospital of Sichuan UniversityChengduChina610041
    53Huashan Hospital Fudan UniversityShanghaiChina200040
    54Hôpital HautepierreStrasbourgFrance67048
    55Hôpital de Brabois AdultesVandoeuvre les NancyFrance54511
    56Charite Campus MitteBerlinGermany10117
    57Universitaetsklinikum FreiburgFreiburgGermany
    58Universitaet KoelnKoelnGermany50937
    59Klinikum St. GeorgLeipzigGermany04129
    60Universitaetsklinik LeipzigLeipzigGermany04289
    61Universitaetsklinikum LeipzigLuebeckGermany
    62Universitaetsklinikum WuerzburgWuerzburgGermany97080
    63Debreceni Egyetem Orvos- es Egeszsegtudomanyi CentrumDebrecenHungary4032
    64Petz Aladar Megyei Oktato KorhazGyörHungary9024
    65Max Super Speciality HospitalNew DelhiDelhiIndia110017
    66Metro Centre for Respiratory DiseasesNoidaDelhiIndia201301
    67Kasturba Medical College and HospitalMangaloreKarnaIndia575001
    68Kasturba Medical College K. M. C. HospitalManipalKarnaIndia576104
    69Amrita Institute Of Medical ScienceCochinKeralaIndia682041
    70Deenanath Mangeshkar Hospital and Research CentrePuneMaharaIndia411004
    71Apollo Hospitals Educational & Research FoundationChennaiIndia
    72Nizam's Institute of Medical SciencesHyderabadIndia500082
    73AMRI HospitalKolkataIndia700098
    74Christian Medical College & HospitalVellore TamilnaduIndia
    75Ha Emek Medical CenterAfulaIsrael18101
    76Rambam Health Care CampusHaifaIsrael31096
    77Wolfson Medical CenterHolonIsrael58100
    78Hadassah Universtiy Hospital - Ein KeremJerusalemIsrael91200
    79Sapir Medical Center, Meir HospitalKfar-SabaIsrael44281
    80Rabin MCPetahIsrael49100
    81Chaim Sheba Medical CenterRamat GanIsrael52621
    82Sourasky MC Ichilov Hospital Tel AvivTel AvivIsrael64239
    83Azienda Ospedaliera Universitaria Policlinico Sant'Orsola MaBolognaItaly40138
    84Azienda Ospedaliera Spedali Civili di BresciaBresciaItaly25126
    85Ente Ospedaliero Ospedeli GallieraGenovaItaly16128
    86Azienda Ospedaliero Universitaria San MartinoGenovaItaly16132
    87Azienda Ospedaliera di Verona-Ospedale Civile MaggioreVeronaItaly37134
    88AUB Medical CenterBeirutLebanon11-0236
    89Rafik Hariri Uni HospitalBeirutLebanon5244
    90Hospital AmpangAmpangMalaysia68000
    91Pusat Perubatan Universiti Kebangsaan MalaysiaKuala LumpurMalaysia56000
    92Hospital Civil de Guadalajara Fray Antonio AlcaldeGuadalajaraMexico44280
    93Hospital Civil de Guadalajara Dr Juan I MenchacaGuadalajaraMexico44340
    94Instituto Nacional de Ciencias Medicas y Nutricion SalvadorMexicoMexico14000
    95Hospital Universitario Dr Jose Eleuterio GonzalezMonterreyMexico64460
    96Auckland City HospitalAucklandNew Zealand
    97Waikato Urology Research LtdHamiltonNew Zealand
    98De La Salle Health Sciences Institute- DLSUMCCavite CityPhilippines
    99Philippine General HospitalManilaPhilippines
    100S.I. Russian Oncological Research Center n.a. N.N. BlokhinMoscowRussian Federation115478
    101State Institution "Hematology Research Center" RAMSMoscowRussian Federation125167
    102Singapore General Hospital - ParentSingaporeSingapore169608
    103National Neuroscience InstituteSingaporeSingapore308433
    104Unitas HospitalLyttelton CenturionSouth Africa0157
    105Hospital del MarBarcelonaSpain08003
    106Hôpitaux Universitaires de Genève - HUGGenevaSwitzerland
    107Universitaetsspital ZuerichZurichSwitzerland
    108Siriraj HospitalBangkoknoiThailand10700
    109Songklanagarind HospitalHat YaiThailand90110
    110Maharat Nakhon Ratchasima HospitalMuangThailand30000
    111Srinagarind HospitalMuangThailand40002
    112Maharaj Nakorn Chiang Mai HospitalMuangThailand50200
    113Ramathibodi HospitalRatchathewiThailand10400

    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 DetailsConsenting 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 DetailParticipants were stratified at randomization by geographical region and baseline neutropenic status.
    Arm/Group TitleIsavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Arm/Group DescriptionParticipants 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
    STARTED223227
    Intent to Treat Population (ITT)221219
    COMPLETED120131
    NOT COMPLETED10396

    Baseline Characteristics

    Arm/Group TitleIsavuconazole (ISA)Caspofungin (CAS)/VoriconazoleTotal
    Arm/Group DescriptionParticipants 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 Participants221219440
    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
    TitlePercentage 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
    DescriptionA 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 FrameEnd 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 TitleIsavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Arm/Group DescriptionParticipants 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 Participants199201
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-10.8
    Confidence Interval (2-Sided) 95%
    -19.9 to -1.8
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    2. Secondary Outcome
    TitlePercentage 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)
    DescriptionA 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 FrameEnd 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 TitleIsavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Arm/Group DescriptionParticipants 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 Participants199201
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-2.7
    Confidence Interval (2-Sided) 95%
    -12.2 to 6.8
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    3. Secondary Outcome
    TitlePercentage 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
    DescriptionA 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 FrameEOT (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 TitleIsavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Arm/Group DescriptionParticipants 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 Participants199201
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference %
    Estimated Value-10.9
    Confidence Interval (2-Sided) 95%
    -19.9 to -1.9
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference %
    Estimated Value-5.4
    Confidence Interval (2-Sided) 95%
    -15.00 to 4.2
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    4. Secondary Outcome
    TitlePercentage of Participants With Clinical Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC)
    DescriptionA 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 FrameEOIV (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 TitleIsavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Arm/Group DescriptionParticipants 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 Participants199201
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-8.2
    Confidence Interval (2-Sided) 95%
    -15.4 to -0.9
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-8.6
    Confidence Interval (2-Sided) 95%
    -15.8 to -1.5
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-0.4
    Confidence Interval (2-Sided) 95%
    -9.1 to 8.3
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-5.8
    Confidence Interval (2-Sided) 95%
    -15.3 to 3.6
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    5. Secondary Outcome
    TitlePercentage of Participants With Mycological Response of Success at EOIV, EOT, FU1 and FU2 as Determined by the Data Review Committee (DRC)
    DescriptionA 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 FrameEOIV (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 TitleIsavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Arm/Group DescriptionParticipants 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 Participants199201
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-14.9
    Confidence Interval (2-Sided) 95%
    -22.7 to -7.0
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-15.9
    Confidence Interval (2-Sided) 95%
    -23.5 to -8.4
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-0.7
    Confidence Interval (2-Sided) 95%
    -8.1 to 9.6
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-5.2
    Confidence Interval (2-Sided) 95%
    -14.7 to 4.3
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    6. Secondary Outcome
    TitlePercentage of Participants With Mycological Response of Success at Day 7 and EOT as Determined by The Investigator
    DescriptionSuccess was defined as mycological response (eradication or presumed eradication).
    Time FrameDay 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 TitleIsavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Arm/Group DescriptionParticipants 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 Participants199201
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-11.4
    Confidence Interval (2-Sided) 95%
    -20.4 to -2.5
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-8.5
    Confidence Interval (2-Sided) 95%
    -16.5 to -0.4
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    7. Secondary Outcome
    TitlePercentage of Participants With Clinical Response of Success at Day 7 and EOT as Determined by The Investigator
    DescriptionInvestigators defined clinical response as success if participants exhibited complete or partial clinical response after evaluation of clinical signs and symptoms.
    Time FrameDay 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 TitleIsavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Arm/Group DescriptionParticipants 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 Participants199201
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-11.1
    Confidence Interval (2-Sided) 95%
    -20.3 to -1.9
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value-8.1
    Confidence Interval (2-Sided) 95%
    -16.3 to 0.1
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 95% CI for the adjusted treatment difference was calculated based on a normal approximation.
    8. Secondary Outcome
    TitleAll-Cause Mortality (ACM) at Day 14 and Day 56
    DescriptionAll-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 FrameDay 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 TitleIsavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Arm/Group DescriptionParticipants 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 Participants199201
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value2.5
    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 Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterAdjusted Treatment Difference (%)
    Estimated Value1.4
    Confidence Interval (2-Sided) 95%
    -7.1 to 10.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    TitleTime to First Confirmed Negative Culture
    DescriptionThe 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 FrameDay 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 TitleIsavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Arm/Group DescriptionParticipants 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 Participants120119
    Median (95% Confidence Interval) [Days]
    4.0
    3.0

    Adverse Events

    Time FrameDay 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 TitleIsavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Arm/Group DescriptionParticipants 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 (%)# EventsAffected / at Risk (%)# Events
    Total55/220 (25%) 55/220 (25%)
    Serious Adverse Events
    Isavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total112/220 (50.9%) 106/220 (48.2%)
    Blood and lymphatic system disorders
    Anaemia1/220 (0.5%) 13/220 (1.4%) 3
    Anaemia haemolytic autoimmune0/220 (0%) 01/220 (0.5%) 1
    Coagulopathy1/220 (0.5%) 10/220 (0%) 0
    Disseminated intravascular coagulation0/220 (0%) 01/220 (0.5%) 1
    Neutropenia1/220 (0.5%) 12/220 (0.9%) 2
    Pancytopenia1/220 (0.5%) 10/220 (0%) 0
    Thrombocytopenia1/220 (0.5%) 10/220 (0%) 0
    Cardiac disorders
    Arrhythmia1/220 (0.5%) 10/220 (0%) 0
    Atrial fibrillation0/220 (0%) 01/220 (0.5%) 1
    Bradycardia1/220 (0.5%) 10/220 (0%) 0
    Cardiac arrest4/220 (1.8%) 66/220 (2.7%) 6
    Cardiac failure0/220 (0%) 02/220 (0.9%) 2
    Cardio-respiratory arrest1/220 (0.5%) 11/220 (0.5%) 1
    Cardiomyopathy0/220 (0%) 01/220 (0.5%) 1
    Coronary artery stenosis0/220 (0%) 01/220 (0.5%) 1
    Hypertensive heart disease0/220 (0%) 01/220 (0.5%) 1
    Myocardial infarction1/220 (0.5%) 11/220 (0.5%) 1
    Pericardial effusion0/220 (0%) 01/220 (0.5%) 1
    Sick sinus syndrome0/220 (0%) 01/220 (0.5%) 1
    Tachycardia1/220 (0.5%) 10/220 (0%) 0
    Torsade de pointes1/220 (0.5%) 10/220 (0%) 0
    Ventricular extrasystoles1/220 (0.5%) 10/220 (0%) 0
    Ventricular fibrillation1/220 (0.5%) 10/220 (0%) 0
    Ventricular tachycardia2/220 (0.9%) 20/220 (0%) 0
    Congenital, familial and genetic disorders
    Sickle cell anaemia with crisis1/220 (0.5%) 10/220 (0%) 0
    Endocrine disorders
    Diabetes insipidus0/220 (0%) 01/220 (0.5%) 1
    Eye disorders
    Vision blurred1/220 (0.5%) 10/220 (0%) 0
    Gastrointestinal disorders
    Abdominal distension0/220 (0%) 01/220 (0.5%) 1
    Abdominal pain0/220 (0%) 02/220 (0.9%) 3
    Ascites0/220 (0%) 01/220 (0.5%) 1
    Diarrhoea2/220 (0.9%) 20/220 (0%) 0
    Duodenal perforation0/220 (0%) 01/220 (0.5%) 1
    Enterocutaneous fistula0/220 (0%) 01/220 (0.5%) 1
    Faecaloma1/220 (0.5%) 10/220 (0%) 0
    Gastrointestinal haemorrhage1/220 (0.5%) 11/220 (0.5%) 1
    Intestinal obstruction1/220 (0.5%) 10/220 (0%) 0
    Intestinal perforation1/220 (0.5%) 10/220 (0%) 0
    Lower gastrointestinal haemorrhage0/220 (0%) 01/220 (0.5%) 1
    Melaena1/220 (0.5%) 10/220 (0%) 0
    Nausea1/220 (0.5%) 12/220 (0.9%) 2
    Pancreatitis1/220 (0.5%) 11/220 (0.5%) 1
    Peritonitis1/220 (0.5%) 11/220 (0.5%) 1
    Proctalgia0/220 (0%) 01/220 (0.5%) 1
    Rectal haemorrhage0/220 (0%) 01/220 (0.5%) 2
    Upper gastrointestinal haemorrhage1/220 (0.5%) 11/220 (0.5%) 1
    Vomiting1/220 (0.5%) 13/220 (1.4%) 3
    General disorders
    Chest discomfort1/220 (0.5%) 10/220 (0%) 0
    Chills0/220 (0%) 01/220 (0.5%) 1
    Death0/220 (0%) 01/220 (0.5%) 1
    Drug withdrawal syndrome1/220 (0.5%) 10/220 (0%) 0
    General physical health deterioration0/220 (0%) 01/220 (0.5%) 1
    Impaired healing1/220 (0.5%) 10/220 (0%) 0
    Multi-organ failure5/220 (2.3%) 57/220 (3.2%) 7
    Necrosis1/220 (0.5%) 10/220 (0%) 0
    Pyrexia2/220 (0.9%) 20/220 (0%) 0
    Systemic inflammatory response syndrome0/220 (0%) 01/220 (0.5%) 1
    Hepatobiliary disorders
    Cholecystitis1/220 (0.5%) 10/220 (0%) 0
    Cholecystitis acute0/220 (0%) 01/220 (0.5%) 1
    Hepatic failure1/220 (0.5%) 12/220 (0.9%) 2
    Hepatosplenomegaly0/220 (0%) 01/220 (0.5%) 1
    Immune system disorders
    Drug hypersensitivity1/220 (0.5%) 20/220 (0%) 0
    Infections and infestations
    Abdominal abscess2/220 (0.9%) 32/220 (0.9%) 2
    Abscess0/220 (0%) 01/220 (0.5%) 1
    Bacteraemia3/220 (1.4%) 30/220 (0%) 0
    Bacterial sepsis3/220 (1.4%) 34/220 (1.8%) 4
    Candida endophthalmitis1/220 (0.5%) 10/220 (0%) 0
    Catheter related infection0/220 (0%) 01/220 (0.5%) 1
    Cellulitis0/220 (0%) 01/220 (0.5%) 1
    Cerebral aspergillosis0/220 (0%) 01/220 (0.5%) 1
    Clostridium difficile colitis1/220 (0.5%) 11/220 (0.5%) 1
    Device related infection1/220 (0.5%) 20/220 (0%) 0
    Diverticulitis1/220 (0.5%) 10/220 (0%) 0
    Enterobacter sepsis0/220 (0%) 01/220 (0.5%) 1
    Escherichia urinary tract infection1/220 (0.5%) 10/220 (0%) 0
    Fungal infection0/220 (0%) 01/220 (0.5%) 1
    Infected skin ulcer1/220 (0.5%) 10/220 (0%) 0
    Infection1/220 (0.5%) 10/220 (0%) 0
    Klebsiella infection0/220 (0%) 01/220 (0.5%) 1
    Klebsiella sepsis2/220 (0.9%) 21/220 (0.5%) 1
    Lung abscess1/220 (0.5%) 10/220 (0%) 0
    Mediastinitis1/220 (0.5%) 10/220 (0%) 0
    Meningitis bacterial1/220 (0.5%) 10/220 (0%) 0
    Neutropenic sepsis2/220 (0.9%) 20/220 (0%) 0
    Pneumonia2/220 (0.9%) 26/220 (2.7%) 6
    Pneumonia staphylococcal0/220 (0%) 01/220 (0.5%) 1
    Postoperative wound infection1/220 (0.5%) 10/220 (0%) 0
    Pseudomonal sepsis0/220 (0%) 01/220 (0.5%) 1
    Sepsis16/220 (7.3%) 169/220 (4.1%) 9
    Septic shock19/220 (8.6%) 1911/220 (5%) 12
    Staphylococcal sepsis0/220 (0%) 01/220 (0.5%) 1
    Streptococcal bacteraemia1/220 (0.5%) 10/220 (0%) 0
    Systemic candida1/220 (0.5%) 11/220 (0.5%) 1
    Tracheobronchitis1/220 (0.5%) 10/220 (0%) 0
    Urinary tract infection bacterial0/220 (0%) 01/220 (0.5%) 1
    Urinary tract infection enterococcal0/220 (0%) 01/220 (0.5%) 1
    Urosepsis0/220 (0%) 02/220 (0.9%) 2
    Wound abscess1/220 (0.5%) 10/220 (0%) 0
    Injury, poisoning and procedural complications
    Brain herniation1/220 (0.5%) 10/220 (0%) 0
    Donor site complication0/220 (0%) 01/220 (0.5%) 1
    Drug toxicity0/220 (0%) 01/220 (0.5%) 1
    Facial bones fracture0/220 (0%) 01/220 (0.5%) 1
    Fall0/220 (0%) 01/220 (0.5%) 1
    Post procedural haemorrhage0/220 (0%) 01/220 (0.5%) 1
    Soft tissue injury1/220 (0.5%) 10/220 (0%) 0
    Subcutaneous haematoma1/220 (0.5%) 20/220 (0%) 0
    Transfusion reaction1/220 (0.5%) 10/220 (0%) 0
    Wound dehiscence0/220 (0%) 01/220 (0.5%) 1
    Wound haemorrhage0/220 (0%) 01/220 (0.5%) 1
    Investigations
    Blood bilirubin increased1/220 (0.5%) 10/220 (0%) 0
    Blood creatinine increased1/220 (0.5%) 10/220 (0%) 0
    C-reactive protein increased1/220 (0.5%) 10/220 (0%) 0
    Hepatic enzyme abnormal0/220 (0%) 01/220 (0.5%) 1
    Hepatic enzyme increased2/220 (0.9%) 22/220 (0.9%) 2
    Liver function test abnormal1/220 (0.5%) 10/220 (0%) 0
    Oxygen saturation decreased3/220 (1.4%) 30/220 (0%) 0
    Metabolism and nutrition disorders
    Diabetic complication1/220 (0.5%) 10/220 (0%) 0
    Diabetic ketoacidosis1/220 (0.5%) 20/220 (0%) 0
    Fluid overload1/220 (0.5%) 10/220 (0%) 0
    Hypernatraemia0/220 (0%) 01/220 (0.5%) 1
    Hypocalcaemia1/220 (0.5%) 10/220 (0%) 0
    Hypoglycaemia0/220 (0%) 01/220 (0.5%) 1
    Hypokalaemia2/220 (0.9%) 23/220 (1.4%) 3
    Hypomagnesaemia1/220 (0.5%) 10/220 (0%) 0
    Hyponatraemia0/220 (0%) 01/220 (0.5%) 1
    Lactic acidosis1/220 (0.5%) 10/220 (0%) 0
    Metabolic acidosis1/220 (0.5%) 10/220 (0%) 0
    Tumour lysis syndrome1/220 (0.5%) 10/220 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia1/220 (0.5%) 10/220 (0%) 0
    Fistula1/220 (0.5%) 10/220 (0%) 0
    Systemic lupus erythematosus0/220 (0%) 01/220 (0.5%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia recurrent0/220 (0%) 01/220 (0.5%) 1
    Breast cancer1/220 (0.5%) 10/220 (0%) 0
    Hodgkin's disease refractory1/220 (0.5%) 10/220 (0%) 0
    Lung neoplasm malignant0/220 (0%) 01/220 (0.5%) 1
    Lymphoma1/220 (0.5%) 11/220 (0.5%) 1
    Malignant neoplasm progression1/220 (0.5%) 10/220 (0%) 0
    Metastases to liver0/220 (0%) 01/220 (0.5%) 1
    Metastases to meninges1/220 (0.5%) 10/220 (0%) 0
    Neoplasm progression0/220 (0%) 01/220 (0.5%) 1
    Non-Hodgkin's lymphoma0/220 (0%) 01/220 (0.5%) 1
    Pancreatic carcinoma1/220 (0.5%) 10/220 (0%) 0
    Sarcoma0/220 (0%) 01/220 (0.5%) 1
    Thyroid neoplasm0/220 (0%) 01/220 (0.5%) 1
    Nervous system disorders
    Basilar artery thrombosis0/220 (0%) 01/220 (0.5%) 1
    Cerebral haemorrhage1/220 (0.5%) 11/220 (0.5%) 1
    Cerebrovascular accident1/220 (0.5%) 10/220 (0%) 0
    Convulsion1/220 (0.5%) 11/220 (0.5%) 1
    Depressed level of consciousness1/220 (0.5%) 10/220 (0%) 0
    Grand mal convulsion1/220 (0.5%) 11/220 (0.5%) 1
    Headache1/220 (0.5%) 10/220 (0%) 0
    Hypoglycaemic encephalopathy0/220 (0%) 01/220 (0.5%) 1
    Hypoxic encephalopathy0/220 (0%) 01/220 (0.5%) 1
    Intracranial haematoma1/220 (0.5%) 10/220 (0%) 0
    Partial seizures0/220 (0%) 01/220 (0.5%) 1
    Somnolence0/220 (0%) 01/220 (0.5%) 1
    Status epilepticus0/220 (0%) 01/220 (0.5%) 1
    Vasogenic cerebral oedema0/220 (0%) 01/220 (0.5%) 1
    Renal and urinary disorders
    Nephrectasia0/220 (0%) 01/220 (0.5%) 1
    Obstructive uropathy0/220 (0%) 01/220 (0.5%) 1
    Renal failure2/220 (0.9%) 22/220 (0.9%) 2
    Renal failure acute10/220 (4.5%) 103/220 (1.4%) 3
    Renal failure chronic0/220 (0%) 01/220 (0.5%) 1
    Urinary retention0/220 (0%) 01/220 (0.5%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema2/220 (0.9%) 20/220 (0%) 0
    Acute respiratory distress syndrome0/220 (0%) 01/220 (0.5%) 1
    Acute respiratory failure2/220 (0.9%) 21/220 (0.5%) 1
    Aspiration1/220 (0.5%) 10/220 (0%) 0
    Atelectasis1/220 (0.5%) 10/220 (0%) 0
    Dyspnoea2/220 (0.9%) 21/220 (0.5%) 1
    Pneumonia aspiration3/220 (1.4%) 32/220 (0.9%) 2
    Pulmonary alveolar haemorrhage1/220 (0.5%) 11/220 (0.5%) 1
    Pulmonary embolism4/220 (1.8%) 42/220 (0.9%) 2
    Pulmonary haemorrhage2/220 (0.9%) 20/220 (0%) 0
    Pulmonary necrosis1/220 (0.5%) 10/220 (0%) 0
    Respiratory distress5/220 (2.3%) 51/220 (0.5%) 1
    Respiratory failure12/220 (5.5%) 138/220 (3.6%) 8
    Skin and subcutaneous tissue disorders
    Stevens-Johnson syndrome0/220 (0%) 01/220 (0.5%) 1
    Vascular disorders
    Arterial thrombosis limb1/220 (0.5%) 10/220 (0%) 0
    Arteriosclerosis0/220 (0%) 01/220 (0.5%) 1
    Deep vein thrombosis2/220 (0.9%) 21/220 (0.5%) 1
    Haematoma1/220 (0.5%) 10/220 (0%) 0
    Haemodynamic instability0/220 (0%) 01/220 (0.5%) 1
    Hypertension1/220 (0.5%) 10/220 (0%) 0
    Hypotension3/220 (1.4%) 31/220 (0.5%) 1
    Hypovolaemic shock1/220 (0.5%) 10/220 (0%) 0
    Jugular vein thrombosis1/220 (0.5%) 10/220 (0%) 0
    Shock2/220 (0.9%) 20/220 (0%) 0
    Shock haemorrhagic2/220 (0.9%) 20/220 (0%) 0
    Other (Not Including Serious) Adverse Events
    Isavuconazole (ISA)Caspofungin (CAS)/Voriconazole
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total162/220 (73.6%) 167/220 (75.9%)
    Blood and lymphatic system disorders
    Anaemia13/220 (5.9%) 1418/220 (8.2%) 21
    Cardiac disorders
    Tachycardia18/220 (8.2%) 209/220 (4.1%) 10
    Gastrointestinal disorders
    Abdominal pain16/220 (7.3%) 1720/220 (9.1%) 23
    Constipation32/220 (14.5%) 3424/220 (10.9%) 31
    Diarrhoea33/220 (15%) 3741/220 (18.6%) 49
    Nausea21/220 (9.5%) 2830/220 (13.6%) 37
    Vomiting33/220 (15%) 4437/220 (16.8%) 49
    General disorders
    Chills11/220 (5%) 156/220 (2.7%) 6
    Oedema peripheral15/220 (6.8%) 1716/220 (7.3%) 17
    Pyrexia38/220 (17.3%) 5641/220 (18.6%) 73
    Infections and infestations
    Bacteraemia11/220 (5%) 129/220 (4.1%) 9
    Staphylococcal bacteraemia13/220 (5.9%) 139/220 (4.1%) 10
    Urinary tract infection bacterial7/220 (3.2%) 712/220 (5.5%) 12
    Investigations
    Blood alkaline phosphatase increased4/220 (1.8%) 411/220 (5%) 12
    Gamma-glutamyltransferase increased5/220 (2.3%) 511/220 (5%) 11
    Metabolism and nutrition disorders
    Hyperkalaemia18/220 (8.2%) 1918/220 (8.2%) 21
    Hypokalaemia41/220 (18.6%) 4944/220 (20%) 50
    Hypomagnesaemia18/220 (8.2%) 2229/220 (13.2%) 31
    Hyponatraemia12/220 (5.5%) 1214/220 (6.4%) 16
    Hypophosphataemia15/220 (6.8%) 159/220 (4.1%) 11
    Musculoskeletal and connective tissue disorders
    Pain in extremity13/220 (5.9%) 156/220 (2.7%) 6
    Psychiatric disorders
    Agitation5/220 (2.3%) 513/220 (5.9%) 15
    Anxiety11/220 (5%) 117/220 (3.2%) 8
    Insomnia12/220 (5.5%) 1310/220 (4.5%) 10
    Respiratory, thoracic and mediastinal disorders
    Cough10/220 (4.5%) 1113/220 (5.9%) 14
    Dyspnoea15/220 (6.8%) 1814/220 (6.4%) 14
    Pleural effusion11/220 (5%) 1112/220 (5.5%) 12
    Skin and subcutaneous tissue disorders
    Decubitus ulcer14/220 (6.4%) 1510/220 (4.5%) 19
    Vascular disorders
    Hypertension9/220 (4.1%) 912/220 (5.5%) 13
    Hypotension22/220 (10%) 3027/220 (12.3%) 29
    Phlebitis14/220 (6.4%) 1415/220 (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/TitleClinical Trial Disclosure
    OrganizationAstellas Pharma Global Development, Inc.
    Phone800-888-7704 ext 5473
    Emailastellas.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