Isavuconazole (BAL8557) in the Treatment of Candidemia and Other Invasive Candida Infections
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
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:
|
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:
Drug: Voriconazole
Administered by intravenous infusion.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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).
- 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).
- 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).
- 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).
- 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.
- 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.
- 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
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.- 9766-CL-0105
- WSA-CS-008
- 2006-003951-18
- NCT00444366
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
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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 |
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
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 |
astellas.resultsdisclosure@astellas.com |
- 9766-CL-0105
- WSA-CS-008
- 2006-003951-18
- NCT00444366