VITAL: Isavuconazole in the Treatment of Renally Impaired Aspergillosis and Rare Fungi

• Sponsor: Astellas Pharma Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00634049
• Collaborator: Basilea Pharmaceutica International Ltd (Industry)
• Enrollment: 149
• Locations: 97
• Arm: 1
• Actual Duration (Months): 96.4
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the efficacy and safety of isavuconazole in the treatment of renally impaired participants with invasive fungal infections caused by Aspergillus and participants with invasive fungal disease caused by rare fungi.

Condition or Disease	Intervention/Treatment	Phase
Aspergillosis; Invasive Fungal Infections	Drug: isavuconazole	Phase 3

Detailed Description

Acute invasive fungal infections caused by aspergillus, rare moulds, yeasts or dimorphic fungi are life threatening diseases. Early treatment with highly effective anti-fungals reduces mortality. This study investigates the safety and efficacy of isavuconazole in participants with aspergillosis and renal impairment, and in participants suffering from invasive infections from rare fungi.

Study Design

• Study Type: Interventional
• Actual Enrollment: 149 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label Study of Isavuconazole in the Treatment of Participants With Aspergillosis and Renal Impairment or of Participants With Invasive Fungal Disease Caused by Rare Moulds, Yeasts or Dimorphic Fungi
• Actual Study Start Date: Apr 22, 2008
• Actual Primary Completion Date: Jan 3, 2014
• Actual Study Completion Date: May 5, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Isavuconazole Administration of isavuconazole 3 times a day in the vein (IV) or oral as a capsule for 2 days followed by daily administration of isavuconazole (IV) or oral	Drug: isavuconazole; Administration of 200 mg isavuconazole 3 times a day in the vein (IV) or oral as a capsule for 2 days, followed by daily administration of 200 mg isavuconazole (IV) or oral; Other Names: BAL8557 ASP9766

Outcome Measures

Primary Outcome Measures

1. Crude Success Rate of Overall Outcome of Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and End of Treatment (EOT). [Day 42, 84 and End of Treatment (EOT [Day 180])]

   The DRC assessed overall response based on individual clinical, mycological and radiological response assessments. Overall response outcomes were described as Success (complete or partial). Complete success was defined as a resolution of all clinical symptoms and physical findings associated with IFD. Partial success was defined as a resolution of at least some clinical symptoms and physical findings associated with IFD End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

Secondary Outcome Measures

1. Crude Success Rate of Clinical Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT [Day 42, 84 and End of Treatment (EOT [Day 180])]

   The DRC evaluated clinical response to treatment at day 42, day 84 and EOT. Clinical response outcomes were described as Success [Resolution of all attributable clinical symptoms and physical findings and Partial resolution of attributable clinical symptoms and physical findings]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

2. Crude Success Rate of Mycological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT [Day 42, 84 and End of Treatment (EOT [Day 180])]

   The DRC evaluated mycological response to treatment at day 42, day 84 and EOT. Mycological response outcomes were described as Success [Eradication and Presumed eradication]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

3. Crude Success Rate of Radiological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT [Day 42, 84 and End of Treatment (EOT [Day 180])]

   The DRC evaluated radiological response to treatment at at day 42, day 84 and EOT. Radiological response outcomes were described as Success [Improvement of at least 25% from baseline for invasive aspergillosis and other filamentous mold infections], [Improvement of at least 50% from baseline for invasive aspergillosis and other filamentous mold infections]; and [Improvement of at least 25% from baseline if EOT occurs prior to day 42 and at least 50% improvement from baseline if EOT occurs after day 42 for invasive aspergillosis and other filamentous mold infections]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

4. Crude Success Rate of Clinical Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT [Day 42, Day 84 and End of Treatment (EOT [Day 180])]

   The Investigator evaluated clinical response to treatment at day 42, day 84 and EOT. Clinical response outcomes were described as Success [Resolution of all attributable clinical symptoms and physical findings] and [Resolution of some attributable clinical symptoms and physical findings]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

5. Crude Success Rate of Mycological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT [Day 42, Day 84 and End of Treatment (EOT [Day 180])]

   The Investigator evaluated mycological response to treatment at day 42, day 84 and EOT. Mycological response outcomes were described as Success [Eradication,Presumed eradication]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

6. Crude Success Rate of Radiological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT [Day 42, Day 84 and End of Treatment (EOT [Day 180])]

   The Investigator evaluated radiological response to treatment at day 42, day 84 and EOT. Radiological response outcomes were described as Success [≥ 90% improvement,≥ 50% to < 90% improvement and ≥ 25% to < 50% improvement (for day 42 and EOT, if EOT occurs prior to day 42)]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

7. All-cause Mortality Through Day 42 and Day 84 [Baseline to End of Treatment (EOT [Day 180])]

   All-cause Mortality was assessed through Day 42 and Day 84 and summarized for ITT population End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.

8. Safety - Overall Number of TEAEs [From the first study drug administration until 28 days after the last dose of study drug]

   A Treatment Emergent Adverse Events (TEAE) is any adverse event that starts after the first administration of study drug until 28 days after the last dose of study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

•Participants meeting EORTC/MSG (European Organization for the Research and Treatment of Cancer/Mycoses Study Group) definition of proven or culture positive probable IFD (invasive fungal disease) caused by rare moulds, yeasts, or dimorphic fungi (i.e. fungal pathogens other than Aspergillus fumigatus or Candida species) whether renally impaired or not (including dialysis) who require primary therapy for their IFD at the time of enrollment.

OR

•Participants who had proven or probable zygomycosis, whether renally impaired or not (including dialysis), who require primary therapy. Zygomycosis must be documented by culture or histology / cytology.

OR

•Participants meeting EORTC/MSG definition of proven or culture positive probable IFD caused by rare moulds, yeasts, or dimorphic fungi (i.e., fungal pathogens other than Aspergillus fumigatus or Candida species), whether RI or not (including dialysis), who were refractory to current treatment defined as,

• Clear documentation of progression of disease. Note: radiological progression only in association with white blood cell (WBC) count recovery was not acceptable.

• Failure to improve clinically despite receiving at least 7 days of standard antifungal regimen. Prior to enrolling patients who fell into this category, the Medical Monitor was contacted for approval.

OR

• Participants meeting EORTC/MSG definition of proven or culture positive probable IFD caused by rare moulds, yeasts, or dimorphic fungi (i.e., fungal pathogens other than Aspergillus fumigatus or Candida species), whether RI or not (including dialysis), who were intolerant to current treatment for example:

• Doubling of serum creatinine value to higher than the upper limit of normal (ULN) within 48 hours.

• Serum creatinine > 2.0 mg/mL and current treatment with polyene or IV voriconazole.

• Other significant drug-related adverse reaction(s) to the current antifungal agent, resulting in discontinuation of the treatment, e.g., persistence of visual disturbance, allergic reaction, phototoxicity or severe infusion reaction (hypertensive crisis, severe chills or shock).

• Documented inability to achieve adequate blood levels of posaconazole, voriconazole or itraconazole.

Exclusion Criteria:

• A known condition of the participants that may jeopardize adherence to the protocol requirements

• Participants who are unlikely to survive 30 days

• Participants with a body weight < 40 kg

• Women who are pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	City Of Hope National Medical Center	Duarte	California	United States	91010
3	University of California Davis Health System	Sacramento	California	United States	95817
4	California Pacific Medical Center	San Francisco	California	United States	94110
5	University of California at San Francisco	San Francisco	California	United States	94143
6	Stanford University Hospital	Stanford	California	United States	94303
7	University Of Colorado Health Sciences Center	Aurora	Colorado	United States	80045
8	Emory Hospital	Atlanta	Georgia	United States	30322
9	University of Chicago, Division of Infectious Diseases	Chicago	Illinois	United States	60637
10	Indiana BMT	Beech Grove	Indiana	United States	46107
11	Infectious Disease of Indiana	Indianapolis	Indiana	United States	46280
12	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
13	Brigham & Womens Hospital	Boston	Massachusetts	United States	02115
14	UMASS Memorial Medical Center	Worcester	Massachusetts	United States	01655
15	Wayne State University School of Medicine	Detroit	Michigan	United States	48201
16	Henry Ford Hospital	Detroit	Michigan	United States	48202
17	University of Minnesota	Minneapolis	Minnesota	United States	55455
18	Upstate Infectious Diseases Association LLP	Albany	New York	United States	12208
19	Cleveland Clinic	Cleveland	Ohio	United States	44195
20	Regional Infection Diseases Infusion Center Inc.	Lima	Ohio	United States	45801
21	Temple University Health Sciences	Philadelphia	Pennsylvania	United States	19140
22	University of Pittsburgh Medical Center Health System	Pittsburgh	Pennsylvania	United States	15213
23	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
24	Fred Hutchinson Cancer Research Center, Clinical Research	Seattle	Washington	United States	98109
25	Hospital Italiano de Buenos Aires	Ciudad Autonoma		Argentina	1181
26	Instituto Medico Especializado Alexander Fleming	Ciudad Autonoma		Argentina	1426
27	Hospital Nuestra Senora de la Misericordia	Cordoba		Argentina	5000
28	Hospital San Roque	Cordoba		Argentina	5000
29	Centro Polivalente de Asistencia e Investigación Clínica - CER San Juan	San Juan		Argentina	5402
30	Mater Medical Centre	South Brisbane		Australia	4101
31	Princess Alexandria Hospital	Woolloongabba		Australia	4102
32	Institut Jules Bordet	Brussels		Belgium	1000
33	Erasme Hospital	Bruxelles		Belgium	1070
34	Universitair Ziekenhuis Gent	Gent		Belgium	9000
35	Universitaire Ziekenhuizen Leuven	Leuven		Belgium	3000
36	Hospital Felicio Rocho	Belo Horizonte		Brazil	30110-908
37	Santa Casa de Misericordia de Belo Horizonte	Belo Horizonte		Brazil	30150-221
38	Hospital das Clinicas da UFPR	Curitiba		Brazil	80060-150
39	Hospital de Clinicas da FMUSP - Ribeirao Preto	Ribeirao Preto		Brazil	14048-900
40	Hospital Universitario Clementino Fraga Filho	Rio de Janeiro		Brazil	21941-913
41	Hospital Universitario de Santa Maria	Santa Maria		Brazil	97105-900
42	Hospital Professor Edmundo Vasconcelos	São Paulo		Brazil	04038-905
43	Hamilton Health Sciences - Henderson Site	Hamilton	Ontario	Canada	L8V 1C3
44	The Ottawa Hospital - General Campus	Ottawa	Ontario	Canada	K1H 8L6
45	Hôpital Maisonneuve - Rosemont	Montreal	Quebec	Canada	H1T 2M4
46	Hôpital Maisonneuve - Rosemont	Montréal	Quebec	Canada	H1T 2M4
47	Hospital Clinico San Borja Arriaran	Santiago		Chile	8320000
48	Alexandria University Hospital	Alexandria		Egypt	21131
49	National Cancer Institute	Cairo		Egypt	11796
50	Nasser Institute	Cairo		Egypt	12655
51	Hôpital Edouard Herriot	Lyon cedex 3		France	69437
52	Institut Paoli Calmette - Marseille	Marseille Cedex 9		France	13273
53	Hotel Dieu	Nantes		France	44093
54	Hôpital Saint-Louis	Paris Cedex 10		France	75475
55	Hopital Hautepierre	Strasbourg Cedex		France	67048
56	Hôpital de Brabois Adultes	Vandoeuvre les Nancy		France	54511
57	Universitaetsklinikum Aachen	Aachen		Germany	52074
58	Charite-Campus Benjamin Franklin	Berlin		Germany	12200
59	Universitaet Koeln	Köln		Germany	50931
60	Klinikum Neuperlach	Muenchen		Germany	81737
61	Medizinische Klinik und Polyklinik II	Würzburg		Germany	97080
62	Medanta Medicity Hospital	Gurgaon	Haryan	India	122001
63	Shirdi Sai Baba Cancer Hospital K. M. C. Hospital	Manipal	Kama	India	576104
64	Tata Memorial Hopital, Department of Anesthesia	Mumbai	Mahara	India	400012
65	Deenanath Mangeshkar Hospital & Research Centre	Pune	Mahara	India	411004
66	Global Hospitals & Health City	Chennai	Tamilna	India	600100
67	Sterling Hospital	Ahmedabad		India	380052
68	Apollo Hospitals	Hyderabad		India	500033
69	Sahyadri Specialty Hospital	Pune		India	411004
70	Rambam Health Care Campus	Haifa		Israel	31096
71	Hadassah Universtiy Hospital - Ein Kerem	Jerusalem		Israel	91200
72	Rabin MC	Petah Tikva		Israel	49100
73	Chaim Sheba Medical Center	Ramat-Gan		Israel	52621
74	Sourasky MC Ichilov Hospital Tel Aviv	Tel Aviv		Israel	64239
75	Soonchunhyang University Bucheon Hospital	Buchon-si		Korea, Republic of	420-767
76	Gachon University Gil Hospital	Incheon		Korea, Republic of	405-760
77	Samsung Medical Center	Seoul		Korea, Republic of	135-710
78	The Catholic University of Korea	Seoul		Korea, Republic of	137-701
79	Asan Medical Center	Seoul		Korea, Republic of	138-736
80	American University of Beirut Medical Center	Beirut		Lebanon	11-0236
81	Clinique Dr. Rizk	Beirut		Lebanon	1107-2130
82	Rafik Hariri University Hospital	Beirut		Lebanon	5244
83	Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara		Mexico	44280
84	Instituto Nacional de Ciencias Medicas y Nutricion Salvador	Mexico City		Mexico	14000
85	Hospital Universitario Dr Jose Eleuterio Gonzalez	Monterrey		Mexico	64460
86	Hospital Central Dr Ignacio Morones Prieto	San Luis Potosi		Mexico	78240
87	Samodzielny Publiczny Centralny Szpital Kliniczny	Warszawa		Poland	02097
88	S.I. Russian Oncological Research Center n.a. N.N. Blokhin	Moscow		Russian Federation	115478
89	State Institution "Hematology Research Center" RAMS	Moscow		Russian Federation	125167
90	Republican Hospital named after V.A. Baranov	Petrozavodsk		Russian Federation	185019
91	St-Petersburg MA Postgraduate Education	St. Petersburg		Russian Federation	194291
92	Private Practice	Lyttleton	Gauteng	South Africa	0157
93	Songklanagarind Hospital	Hat Yai		Thailand	90110
94	Maharat Nakhon Ratchasima Hospital	Muang		Thailand	30000
95	Srinagarind Hospital	Muang		Thailand	40002
96	Maharaj Nakorn Chiang Mai Hospital	Muang		Thailand	50200
97	Ramathibodi Hospital	Ratchathewi		Thailand	10400

Sponsors and Collaborators

• Astellas Pharma Inc
• Basilea Pharmaceutica International Ltd

Investigators

• Study Director: Medical Director, Astellas Pharma Global Development

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Link to results on Astellas Clinical Study Results website

Publications

None provided.

• Responsible Party: Astellas Pharma Inc
• ClinicalTrials.gov Identifier: NCT00634049
• Other Study ID Numbers: 9766-CL-0103; WSA-CS-003; 2006-005003-33
• First Posted: Mar 12, 2008
• Last Update Posted: Jan 2, 2018
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Astellas Pharma Inc: invasive fungal infections caused by rare molds, rare yeasts; BAL8557; Isavuconazole; Aspergillosis; or by dimorphic fungi; ASP9766
• Additional relevant MeSH terms: Mycoses; Aspergillosis; Invasive Fungal Infections; Isavuconazole

Study Results

Participant Flow

Recruitment Details	Consenting adult participants with proven, probable or possible invasive aspergillosis and renally impaired (RI) or of participants with invasive fungal disease (IFD) caused by rare moulds, yeasts or dimorphic fungi meeting the inclusion and none of the exclusion criteria were considered for entry into the study.
Pre-assignment Detail	Analysis and interpretation of the results was pathogen dependent and each pathogen was quite rare, therefore it was not feasible to enroll a sufficient number of participants in a randomized controlled trial to power the study adequately to allow statistical comparisons.

Arm/Group Title	Isavuconazole
Arm/Group Description	Participants received a loading dose of isavuconazole, 200 mg three times a day administered intravenously (IV) or orally (PO) [or per os (PO)] for the first 2 days followed by a maintenance dose from Day 3 of 200 mg once daily either IV or orally until they reached a treatment endpoint or for a maximum of 180 days; with an option for extended treatment under specified criteria.
Period Title: Overall Study
STARTED	149
COMPLETED	146
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Isavuconazole
Arm/Group Description	Participants received a loading dose of isavuconazole, 200 mg three times a day administered intravenously (IV) or orally (PO) [or per os (PO)] for the first 2 days followed by a maintenance dose from Day 3 of 200 mg once daily either IV or orally until they reached a treatment endpoint or for a maximum of 180 days; with an option for extended treatment under specified criteria.
Overall Participants	146
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.9 (16.78)
Sex: Female, Male (Count of Participants)
Female	46 31.5%
Male	100 68.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	24 16.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	10 6.8%
White	108 74%
More than one race	0 0%
Unknown or Not Reported	4 2.7%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	22 15.1%
Not Hispanic or Latino	124 84.9%
Region of Enrollment (participants) [Number]
Brazil	20 13.7%
India	5 3.4%
Israel	21 14.4%
Lebanon	1 0.7%
Mexico	8 5.5%
Russian Federation	2 1.4%
Korea, Republic of	2 1.4%
Thailand	14 9.6%
Belgium	13 8.9%
Germany	4 2.7%
United States	56 38.4%
Therapy status (participants) [Number]
Primary Therapy	93 63.7%
Refractory	38 26%
Intolerant	12 8.2%
Missing	3 2.1%
Hematologic malignancy (participants) [Number]
Yes	63 43.2%
No	83 56.8%
Allogeneic Bone Marrow Transplant (BMT)/Hematopoietic Stem Cell Transplant (HSCT) (participants) [Number]
Yes	26 17.8%
No	120 82.2%
Uncontrolled malignancy (participants) [Number]
Yes	46 31.5%
No	100 68.5%
Neutropenic (participants) [Number]
Yes	38 26%
No	66 45.2%
Missing	42 28.8%
Corticosteroid use (participants) [Number]
Yes	35 24%
No	111 76%
T-cell immunosuppressant use (participants) [Number]
Yes	61 41.8%
No	48 32.9%
Missing	37 25.3%

Outcome Measures

1. Primary Outcome

Title	Crude Success Rate of Overall Outcome of Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and End of Treatment (EOT).
Description	The DRC assessed overall response based on individual clinical, mycological and radiological response assessments. Overall response outcomes were described as Success (complete or partial). Complete success was defined as a resolution of all clinical symptoms and physical findings associated with IFD. Partial success was defined as a resolution of at least some clinical symptoms and physical findings associated with IFD End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Time Frame	Day 42, 84 and End of Treatment (EOT [Day 180])

Outcome Measure Data

Analysis Population Description

Modified Intent-To-Treat population (mITT)

Arm/Group Title	mITT - Aspergillus [Renally Impaired]	mITT - Aspergillus [Not Renally Impaired]	mITT - Mucorales (Primary Therapy)	mITT - Mucorales (Refractory)	mITT - Mucorales (Intolerant)	mITT- Other Filamentous Fungi	mITT- Other Mould Species Only	mITT- Other Dimorphic Fungi	mITT- Other Non-Candida Yeast	mITT-Other Mixed Infection
Arm/Group Description	Aspergillus - Renally Impaired (RI) mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status, and whether they are renally impaired and not renally impaired. Renal impairment was defined as yes for participants who had a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for patients who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).	Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).	Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.	Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior antifungal therapy (AFT)	Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior antifungal therapy (AFT).	Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).	Other Mould Species mITT population consisted of 7 participants who had proven or probable IFD as determined by the DRC caused by mould species.	Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).	Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).	Other Mixed Infections mITT group consisted of 15 participants who had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Measure Participants	20	4	21	11	5	17	7	29	11	15
Day 42- Success Rate	25.0 17.1%	50.0 NaN	14.3 NaN	9.1 NaN	0 NaN	47.1 NaN	28.6 NaN	41.4 NaN	36.4 NaN	13.3 NaN
Day 84 - Success Rate	30.0 20.5%	25.0 NaN	9.5 NaN	36.4 NaN	20.0 NaN	41.2 NaN	28.6 NaN	44.8 NaN	36.4 NaN	13.3 NaN
End of Treatment (EOT) - Success Rate	30.0 20.5%	66.7 NaN	31.6 NaN	36.4 NaN	20.0 NaN	64.7 NaN	28.6 NaN	64.3 NaN	72.7 NaN	14.3 NaN

2. Secondary Outcome

Title	Crude Success Rate of Clinical Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT
Description	The DRC evaluated clinical response to treatment at day 42, day 84 and EOT. Clinical response outcomes were described as Success [Resolution of all attributable clinical symptoms and physical findings and Partial resolution of attributable clinical symptoms and physical findings]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Time Frame	Day 42, 84 and End of Treatment (EOT [Day 180])

Outcome Measure Data

Analysis Population Description

Modified Intent-To-Treat population (mITT)

Arm/Group Title	mITT - Aspergillus [Renally Impaired]	mITT - Aspergillus [Not Renally Impaired]	mITT - Mucorales (Primary Therapy)	mITT - Mucorales (Refractory)	mITT - Mucorales (Intolerant)	mITT-Other Filamentous Fungi	mITT- Other Mould Species Only	mITT- Other Dimorphic Fungi	mITT- Other Non-Candida Yeast	mITT-Other Mixed Infection
Arm/Group Description	Aspergillus - Renally Impaired (RI) mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status, and whether they are renally impaired or not renally impaired. Renal impairment was defined as yes for participants who had a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for patients who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).	Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).	Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.	Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT.	Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.	Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).	Other Mould Species mITT population consisted of 7 participants who have had proven or probable IFD as determined by the DRC caused by mould species.	Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).	Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).	Other Mixed Infections mITT group consisted of 15 participants who had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Measure Participants	20	4	21	11	5	17	7	29	11	15
Day 42- Success Rate	55.0 37.7%	75.0 NaN	50.0 NaN	33.3 NaN	50.0 NaN	68.8 NaN	71.4 NaN	79.3 NaN	70.0 NaN	42.9 NaN
Day 84 - Success Rate	45.0 30.8%	25.0 NaN	40.0 NaN	22.2 NaN	50.0 NaN	62.5 NaN	42.9 NaN	82.8 NaN	70.0 NaN	35.7 NaN
End of Treatment (EOT) - Success Rate	55.0 37.7%	66.7 NaN	55.6 NaN	22.2 NaN	50.0 NaN	81.3 NaN	85.7 NaN	82.1 NaN	70.0 NaN	38.5 NaN

3. Secondary Outcome

Title	Crude Success Rate of Mycological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT
Description	The DRC evaluated mycological response to treatment at day 42, day 84 and EOT. Mycological response outcomes were described as Success [Eradication and Presumed eradication]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Time Frame	Day 42, 84 and End of Treatment (EOT [Day 180])

Outcome Measure Data

Analysis Population Description

Modified Intent-To-Treat population (mITT)

Arm/Group Title	mITT - Aspergillus [Renally Impaired]	mITT - Aspergillus [Not Renally Impaired]	mITT - Mucorales (Primary Therapy)	mITT - Mucorales (Refractory)	mITT - Mucorales (Intolerant)	mITT-Other Filamentous Fungi	mITT- Other Mould Species Only	mITT- Other Dimorphic Fungi	mITT- Other Non-Candida Yeast	mITT-Other Mixed Infection
Arm/Group Description	Aspergillus - Renally Impaired mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participants IFD. The Aspergillus-mITT population was presented by renal status, renally impaired and not renally impaired. Renal impairment was defined as yes for participants who have a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for participants who have a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).	Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).	Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.	Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT.	Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.	Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).	Other Mould Species mITT population consisted of 7 participants who have had proven or probable IFD as determined by the DRC caused by mould species.	Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).	Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).	Other Mixed Infections mITT population consisted of 15 participants who have had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Measure Participants	20	4	21	11	5	17	7	29	11	15
Day 42- Success Rate	30.0 20.5%	50.0 NaN	4.8 NaN	0 NaN	0 NaN	29.4 NaN	28.6 NaN	27.6 NaN	45.5 NaN	13.3 NaN
Day 84 - Success Rate	35.0 24%	25.0 NaN	9.5 NaN	27.3 NaN	40.0 NaN	35.3 NaN	28.6 NaN	27.6 NaN	45.5 NaN	13.3 NaN
End of Treatment (EOT) - Success Rate	35.0 24%	66.7 NaN	31.6 NaN	36.4 NaN	40.0 NaN	70.6 NaN	28.6 NaN	53.6 NaN	81.8 NaN	14.3 NaN

4. Secondary Outcome

Title	Crude Success Rate of Radiological Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT
Description	The DRC evaluated radiological response to treatment at at day 42, day 84 and EOT. Radiological response outcomes were described as Success [Improvement of at least 25% from baseline for invasive aspergillosis and other filamentous mold infections], [Improvement of at least 50% from baseline for invasive aspergillosis and other filamentous mold infections]; and [Improvement of at least 25% from baseline if EOT occurs prior to day 42 and at least 50% improvement from baseline if EOT occurs after day 42 for invasive aspergillosis and other filamentous mold infections]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Time Frame	Day 42, 84 and End of Treatment (EOT [Day 180])

Outcome Measure Data

Analysis Population Description

Modified Intent-To-Treat population (mITT)

Arm/Group Title	mITT - Aspergillus [Renally Impaired]	mITT - Aspergillus [Not Renally Impaired]	mITT - Mucorales (Primary Therapy)	mITT - Mucorales (Refractory)	mITT - Mucorales (Intolerant)	mITT-Other Filamentous Fungi	mITT- Other Mould Species Only	mITT- Other Dimorphic Fungi	mITT- Other Non-Candida Yeast	mITT-Other Mixed Infection
Arm/Group Description	Aspergillus - Renally Impaired mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participants IFD. The Aspergillus-mITT population was presented by renal status, renally impaired and not renally impaired. Renal impairment was defined as yes for participants who have a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for participants who have a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).	Aspergillus - Renally Impaired mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participants IFD. The Aspergillus-mITT population was presented by renal status, renally impaired and not renally impaired. Overall there were 24 participants in the mITTAspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).	Mucorales - Primary Therapy mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.	Mucorales - Refractory Therapy mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT.	Mucorales - Intolerant mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.	Other Filamentous Fungi mITT population consisted of 17 participants who have had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium,2 Exophiala,2 Cladosporium,2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia,Exserohilum, Paecilomyces,Pseudallescheria and Scedosporium).	Other Mould Species mITT population consisted of 7 participants who have had proven or probable IFD as determined by the DRC caused by mould species.	Other Dimorphic Fungi mITT population consisted of 29 participants who have had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes,9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).	Other Non Candida Yeast mITT population consisted of 11 participants who have had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus NOS and 2 Trichosporon).	Other Mixed Infections mITT population consisted of 15 participants who have had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Measure Participants	20	4	21	11	5	17	7	29	11	15
Day 42- Success Rate	30.0 20.5%	25.0 NaN	0 NaN	10.0 NaN	0 NaN	25.0 NaN	16.7 NaN	21.4 NaN	0 NaN	7.1 NaN
Day 84 - Success Rate	20.0 13.7%	25.0 NaN	4.8 NaN	20.0 NaN	20.0 NaN	6.3 NaN	0 NaN	28.6 NaN	10.0 NaN	14.3 NaN
End of Treatment (EOT) - Success Rate	15.0 10.3%	66.7 NaN	16.7 NaN	20.0 NaN	20.0 NaN	50.0 NaN	0 NaN	33.3 NaN	10.0 NaN	7.7 NaN

5. Secondary Outcome

Title	Crude Success Rate of Clinical Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT
Description	The Investigator evaluated clinical response to treatment at day 42, day 84 and EOT. Clinical response outcomes were described as Success [Resolution of all attributable clinical symptoms and physical findings] and [Resolution of some attributable clinical symptoms and physical findings]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Time Frame	Day 42, Day 84 and End of Treatment (EOT [Day 180])

Outcome Measure Data

Analysis Population Description

Modified Intent-To-Treat population (mITT)

Arm/Group Title	mITT - Aspergillus [Renally Impaired]	mITT - Aspergillus [Not Renally Impaired]	mITT - Mucorales (Primary Therapy)	mITT - Mucorales (Refractory)	mITT - Mucorales (Intolerant)	mITT- Other Filamentous Fungi	mITT- Other Mould Species Only	mITT- Other Dimorphic Fungi	mITT- Other Non-Candida Yeast	mITT-Other Mixed Infection
Arm/Group Description	Aspergillus - Renally Impaired (RI) mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status, and whether they are renally impaired and not renally impaired. Renal impairment was defined as yes for participants who had a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for participants who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).	Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).	Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.	Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT	Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.	Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).	Other Mould Species mITT population consisted of 7 participants who had proven or probable IFD as determined by the DRC caused by mould species.	Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).	Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).	Other Mixed Infections mITT group consisted of 15 participants who had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Measure Participants	20	4	21	11	5	17	7	29	11	15
Day 42	60.0 41.1%	75.0 NaN	50.0 NaN	28.6 NaN	25.0 NaN	81.3 NaN	85.7 NaN	75.9 NaN	70.0 NaN	50.0 NaN
Day 84	55.0 37.7%	55.0 NaN	21.4 NaN	25.0 NaN	20.0 NaN	62.5 NaN	42.9 NaN	82.2 NaN	70.0 NaN	35.7 NaN
End of Treatment (EOT)	60.0 41.1%	75.0 NaN	42.9 NaN	28.6 NaN	66.7 NaN	81.3 NaN	71.4 NaN	79.3 NaN	70.0 NaN	42.9 NaN

6. Secondary Outcome

Title	Crude Success Rate of Mycological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT
Description	The Investigator evaluated mycological response to treatment at day 42, day 84 and EOT. Mycological response outcomes were described as Success [Eradication,Presumed eradication]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Time Frame	Day 42, Day 84 and End of Treatment (EOT [Day 180])

Outcome Measure Data

Analysis Population Description

Modified Intent-To-Treat population (mITT)

Arm/Group Title	mITT - Aspergillus [Renally Impaired]	mITT - Aspergillus [Not Renally Impaired]	mITT - Mucorales (Primary Therapy)	mITT - Mucorales (Refractory)	mITT - Mucorales (Intolerant)	mITT- Other Filamentous Fungi	mITT- Other Mould Species Only	mITT- Other Dimorphic Fungi	mITT- Other Non-Candida Yeast	mITT-Other Mixed Infection
Arm/Group Description	Aspergillus - Renally Impaired (RI) mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status, and whether they are renally impaired and not renally impaired. Renal impairment was defined as yes for participants who had a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for patients who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).	Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).	Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.	Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT	Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.	Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).	Other Mould Species mITT population consisted of 7 participants who had proven or probable IFD as determined by the DRC caused by mould species.	Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).	Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).	Other Mixed Infections mITT group consisted of 15 participants who had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Measure Participants	20	4	21	11	2	17	7	29	11	15
Day 42	46.7 32%	66.7 NaN	50.0 NaN	28.6 NaN	25.0 NaN	69.2 NaN	83.3 NaN	70.6 NaN	50.0 NaN	18.2 NaN
Day 84	44.4 30.4%	50.0 NaN	21.4 NaN	25.0 NaN	20.0 NaN	64.3 NaN	42.9 NaN	80.0 NaN	25.0 NaN	33.3 NaN
End of Treatment (EOT)	50.0 34.2%	66.7 NaN	42.9 NaN	28.6 NaN	66.7 NaN	78.6 NaN	66.7 NaN	76.9 NaN	50.0 NaN	25.0 NaN

7. Secondary Outcome

Title	Crude Success Rate of Radiological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT
Description	The Investigator evaluated radiological response to treatment at day 42, day 84 and EOT. Radiological response outcomes were described as Success [≥ 90% improvement,≥ 50% to < 90% improvement and ≥ 25% to < 50% improvement (for day 42 and EOT, if EOT occurs prior to day 42)]. End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Time Frame	Day 42, Day 84 and End of Treatment (EOT [Day 180])

Outcome Measure Data

Analysis Population Description

Modified Intent-To-Treat population (mITT)

Arm/Group Title	mITT - Aspergillus [Renally Impaired]	mITT - Aspergillus [Not Renally Impaired]	mITT - Mucorales (Primary Therapy)	mITT - Mucorales (Refractory)	mITT - Mucorales (Intolerant)	mITT- Other Filamentous Fungi	mITT- Other Mould Species Only	mITT- Other Dimorphic Fungi	mITT- Other Non-Candida Yeast	mITT-Other Mixed Infection
Arm/Group Description	Aspergillus - Renally Impaired (RI) mITT population consisted of participants who have had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status, and whether they are renally impaired and not renally impaired. Renal impairment was defined as yes for participants who had a baseline estimated glomerular filtration rate (eGFR-MDRD) < 60 mL/min/1.73 m^2, no for participants who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).	Aspergillus - Not Renally Impaired (NRI) mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).	Mucorales - Primary Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 21 participants receiving isavuconazole as a primary therapy.	Mucorales - Refractory Therapy mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participants had proven and 5 participants had probable invasive mucormycosis).The DRC also categorized each patient by therapy status; these groups were primary therapy, refractory and intolerant. There were 11 participants whose IFD was refractory to prior AFT	Mucorales - Intolerant mITT population consisted of participants who had proven or probable IFD as determined by the DRC. Based on the DRC assessment 37 participants were assessed to have proven or probable Mucorales infection (32 participant had proven and 5 participants had probable invasive mucormycosis). The DRC also categorized each participant by therapy status; these groups were primary therapy, refractory and intolerant. There were 5 participants who were intolerant to prior AFT.	Other Filamentous Fungi mITT population consisted of 17 participants who had proven or probable IFD as determined by the DRC caused by other filamentous fungi (4 Fusarium, 2 Exophiala, 2 Cladosporium, 2 Scopulariopsis and 1 each of Acremonium, Alternaria, Curvularia, Exserohilum, Paecilomyces, Pseudallescheria and Scedosporium).	Other Mould Species mITT population consisted of 7 participants who had proven or probable IFD as determined by the DRC caused by mould species.	Other Dimorphic Fungi mITT population consisted of 29 participants who had proven or probable IFD as determined by the DRC caused by dimorphic fungi (10 Paracoccidiodes, 9 Coccidiodides, 7 Histoplasma, 3 Blastomyces).	Other non-Candida Yeast mITT population consisted of 11 participants who had proven or probable IFD as determined by the DRC caused by non-Candida yeast (4 Cryptococcus neoformans, 3 Cryptococcus gatii, 2 Cryptococcus not otherwise specified (NOS) and 2 Trichosporon).	Other Mixed Infections mITT group consisted of 15 participants who had proven or probable IFD as determined by the DRC caused by mixed infections aspergillosis/mucormycosis.
Measure Participants	20	4	21	11	5	17	7	29	11	15
Day 42	35.0 24%	75.0 NaN	40.0 NaN	0 NaN	40.0 NaN	46.7 NaN	20.0 NaN	32.1 NaN	9.1 NaN	28.6 NaN
Day 84	40.0 27.4%	50.0 NaN	25.0 NaN	11.1 NaN	40.0 NaN	40.0 NaN	20.0 NaN	37.0 NaN	0 NaN	7.1 NaN
End of Treatment (EOT)	35.0 24%	50.0 NaN	30.0 NaN	22.2 NaN	20.0 NaN	33.3 NaN	40.0 NaN	55.6 NaN	10.0 NaN	14.3 NaN

8. Secondary Outcome

Title	All-cause Mortality Through Day 42 and Day 84
Description	All-cause Mortality was assessed through Day 42 and Day 84 and summarized for ITT population End of treatment (EOT) is the last day of study drug administration, with an estimated duration up to 180 days.
Time Frame	Baseline to End of Treatment (EOT [Day 180])

Outcome Measure Data

Analysis Population Description

Intent-To-Treat population (ITT)

Arm/Group Title	Renally Impaired	Not Renally Impaired
Arm/Group Description	Renally Impaired (RI) population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. Renal impairment was defined as yes for participants who had a baseline eGFR-MDRD < 60 mL/min/1.73 m^2, no for patients who had a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2. Overall there were 24 participants in the mITT-Aspergillus population out of which 20 participants were classified as Renally Impaired (RI).	Not Renally Impaired (NRI) population consisted of participants who had proven or probable IFD as determined by the DRC. Classification by the DRC was based on the type of pathogen which was found to be the cause of participant's IFD. The Aspergillus-mITT population was presented by renal status (Renally Impaired and Not Renally Impaired). Overall there were 24 participants in the mITT- Aspergillus population out of which 4 participants were classified as Not Renally Impaired (NRI).
Measure Participants	59	87
All-cause Mortality Through Day 42	22.0 15.1%	16.1 NaN
All-cause Mortality Through Day 84	30.5 20.9%	20.7 NaN

9. Secondary Outcome

Title	Safety - Overall Number of TEAEs
Description	A Treatment Emergent Adverse Events (TEAE) is any adverse event that starts after the first administration of study drug until 28 days after the last dose of study drug.
Time Frame	From the first study drug administration until 28 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

The safety analysis set (SAF) consists of all enrolled participants who received at least one dose of study drug as this was a non-comparative open-label study

Arm/Group Title	Isavuconazole
Arm/Group Description	Participants received Isavuconazole intravenous (IV) or per oral (PO) over period of 2 days, on days 1 and 2 three doses of 200 mg were administered every 8 hours for a total of six doses. From Day 3 to End of Treatment (EOT) maintenance dose of 200 mg isavuconazole was administered once daily up to 180 days; with an option for extended treatment under specified criteria.
Measure Participants	146
TEAEs	139 95.2%
Study Drug-Related TEAEs	60 41.1%
Serious TEAEs	89 61%
Study Drug-Related Serious TEAEs	13 8.9%
TEAEs Leading to Permanent Discontinuation of Stud	19 13%
Study Drug TEAEs Leading to Perm Discontinuation	7 4.8%
TEAEs Leading to Death	44 30.1%
Study Drug-Related TEAEs Leading to Death	1 0.7%
Deaths	47 32.2%
Deaths Through 28 Days after Last Dose Study Drug	42 28.8%

Adverse Events

Time Frame	From the first administration of study drug until 28 days after the last dose of study drug. For the days when IV and oral doses were administered on the same day, the day was split into one-half day for each route's duration.
Adverse Event Reporting Description	The safety analysis set is identical to the intent -to-treat (ITT) population (i.e., all enrolled participants who received at least one dose of study drug) as this was a non-comparative open-label study.
Arm/Group Title	Renally Impaired (RI)		Not Renally Impaired (NRI)
Arm/Group Description	Renal impairment was defined as yes for participants who have a baseline as eGFR < 60 mL/min/1.73 m^2 by the Modification of Diet in Renal Disease (MDRD) formula.		Not Renally impaired participants were defined as no if they have a baseline eGFR-MDRD ≥ 60 mL/min/1.73 m^2 by the Modification of Diet in Renal Disease (MDRD) formula.
All Cause Mortality
	Renally Impaired (RI)		Not Renally Impaired (NRI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Renally Impaired (RI)		Not Renally Impaired (NRI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/59 (72.9%)		46/87 (52.9%)
Blood and lymphatic system disorders
Anaemia	1/59 (1.7%)		1/87 (1.1%)
Febrile neutropenia	1/59 (1.7%)		1/87 (1.1%)
Pancytopenia	0/59 (0%)		1/87 (1.1%)
Cardiac disorders
Acute myocardial infarction	1/59 (1.7%)		0/87 (0%)
Atrial fibrillation	2/59 (3.4%)		0/87 (0%)
Atrioventricular block complete	1/59 (1.7%)		0/87 (0%)
Cardiac failure acute	0/59 (0%)		1/87 (1.1%)
Cardio-respiratory arrest	1/59 (1.7%)		1/87 (1.1%)
Electromechanical dissociation	1/59 (1.7%)		0/87 (0%)
Eye disorders
Retinal artery occlusion	0/59 (0%)		1/87 (1.1%)
Retinal haemorrhage	1/59 (1.7%)		0/87 (0%)
Vitreous haemorrhage	1/59 (1.7%)		0/87 (0%)
Gastrointestinal disorders
Abdominal pain	2/59 (3.4%)		3/87 (3.4%)
Colitis	0/59 (0%)		1/87 (1.1%)
Colitis ulcerative	0/59 (0%)		1/87 (1.1%)
Constipation	1/59 (1.7%)		0/87 (0%)
Diarrhoea	1/59 (1.7%)		1/87 (1.1%)
Dysphagia	1/59 (1.7%)		1/87 (1.1%)
Gastrointestinal haemorrhage	3/59 (5.1%)		0/87 (0%)
Localised intraabdominal fluid collection	0/59 (0%)		1/87 (1.1%)
Nausea	0/59 (0%)		2/87 (2.3%)
Oesophagitis	0/59 (0%)		1/87 (1.1%)
Pancreatitis	0/59 (0%)		1/87 (1.1%)
Pancreatitis chronic	0/59 (0%)		1/87 (1.1%)
Pancreatitis relapsing	0/59 (0%)		1/87 (1.1%)
Vomiting	0/59 (0%)		4/87 (4.6%)
General disorders
Death	1/59 (1.7%)		2/87 (2.3%)
General physical health deterioration	1/59 (1.7%)		0/87 (0%)
Multi-organ failure	0/59 (0%)		1/87 (1.1%)
Non-cardiac chest pain	1/59 (1.7%)		1/87 (1.1%)
Oedema peripheral	1/59 (1.7%)		0/87 (0%)
Pyrexia	1/59 (1.7%)		1/87 (1.1%)
Hepatobiliary disorders
Acute hepatic failure	0/59 (0%)		1/87 (1.1%)
Cholangiolitis	1/59 (1.7%)		0/87 (0%)
Cholecystitis	1/59 (1.7%)		0/87 (0%)
Cholelithiasis	1/59 (1.7%)		0/87 (0%)
Liver disorder	0/59 (0%)		1/87 (1.1%)
Immune system disorders
Acute graft versus host disease	2/59 (3.4%)		0/87 (0%)
Graft versus host disease	1/59 (1.7%)		1/87 (1.1%)
Lung transplant rejection	0/59 (0%)		1/87 (1.1%)
Infections and infestations
Abdominal abscess	0/59 (0%)		1/87 (1.1%)
Appendicitis	0/59 (0%)		1/87 (1.1%)
Aspergillosis	1/59 (1.7%)		2/87 (2.3%)
BK virus infection	1/59 (1.7%)		0/87 (0%)
Bacteraemia	3/59 (5.1%)		0/87 (0%)
Bacterial sepsis	1/59 (1.7%)		0/87 (0%)
Brain abscess	1/59 (1.7%)		0/87 (0%)
Bronchiectasis	0/59 (0%)		1/87 (1.1%)
Bronchiolitis	1/59 (1.7%)		0/87 (0%)
Catheter site infection	0/59 (0%)		1/87 (1.1%)
Clostridium difficile colitis	1/59 (1.7%)		0/87 (0%)
Cytomegalovirus enteritis	0/59 (0%)		1/87 (1.1%)
Cytomegalovirus infection	1/59 (1.7%)		1/87 (1.1%)
Empyema	1/59 (1.7%)		0/87 (0%)
Enterococcal bacteraemia	0/59 (0%)		1/87 (1.1%)
Escherichia bacteraemia	0/59 (0%)		1/87 (1.1%)
Escherichia sepsis	1/59 (1.7%)		0/87 (0%)
Fungal infection	0/59 (0%)		1/87 (1.1%)
Fungal sepsis	1/59 (1.7%)		0/87 (0%)
Gastroenteritis norovirus	1/59 (1.7%)		0/87 (0%)
Gastroenteritis viral	0/59 (0%)		1/87 (1.1%)
Herpes zoster	0/59 (0%)		2/87 (2.3%)
Influenza	0/59 (0%)		1/87 (1.1%)
Lung infection	0/59 (0%)		1/87 (1.1%)
Lung infection pseudomonal	1/59 (1.7%)		0/87 (0%)
Mucormycosis	0/59 (0%)		2/87 (2.3%)
Pneumocystis jiroveci pneumonia	1/59 (1.7%)		0/87 (0%)
Pneumonia	1/59 (1.7%)		6/87 (6.9%)
Pneumonia bacterial	1/59 (1.7%)		2/87 (2.3%)
Pneumonia blastomyces	1/59 (1.7%)		0/87 (0%)
Pneumonia fungal	0/59 (0%)		2/87 (2.3%)
Pneumonia influenzal	1/59 (1.7%)		0/87 (0%)
Pneumonia primary atypical	1/59 (1.7%)		0/87 (0%)
Pseudomonal sepsis	0/59 (0%)		2/87 (2.3%)
Pseudomonas bronchitis	1/59 (1.7%)		0/87 (0%)
Sepsis	2/59 (3.4%)		1/87 (1.1%)
Septic shock	6/59 (10.2%)		0/87 (0%)
Sinusitis	1/59 (1.7%)		0/87 (0%)
Sinusitis fungal	0/59 (0%)		1/87 (1.1%)
Staphylococcal bacteraemia	1/59 (1.7%)		0/87 (0%)
Staphylococcal infection	0/59 (0%)		1/87 (1.1%)
Staphylococcal sepsis	0/59 (0%)		1/87 (1.1%)
Streptococcal bacteraemia	0/59 (0%)		1/87 (1.1%)
Subcutaneous abscess	0/59 (0%)		1/87 (1.1%)
Urinary tract infection	1/59 (1.7%)		0/87 (0%)
Urosepsis	1/59 (1.7%)		0/87 (0%)
Viral diarrhoea	1/59 (1.7%)		0/87 (0%)
Zygomycosis	0/59 (0%)		2/87 (2.3%)
Metabolism and nutrition disorders
Dehydration	2/59 (3.4%)		1/87 (1.1%)
Hyperkalaemia	1/59 (1.7%)		0/87 (0%)
Hypoglycaemia	0/59 (0%)		1/87 (1.1%)
Hyponatraemia	0/59 (0%)		1/87 (1.1%)
Malnutrition	0/59 (0%)		1/87 (1.1%)
Musculoskeletal and connective tissue disorders
Arthritis	0/59 (0%)		1/87 (1.1%)
Musculoskeletal chest pain	2/59 (3.4%)		0/87 (0%)
Pain in extremity	1/59 (1.7%)		0/87 (0%)
Systemic lupus erythematosus	0/59 (0%)		1/87 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia recurrent	0/59 (0%)		1/87 (1.1%)
Acute myeloid leukaemia	2/59 (3.4%)		0/87 (0%)
Acute myeloid leukaemia recurrent	0/59 (0%)		2/87 (2.3%)
Chronic lymphocytic leukaemia	0/59 (0%)		1/87 (1.1%)
Malignant neoplasm progression	0/59 (0%)		2/87 (2.3%)
Leukaemia recurrent	1/59 (1.7%)		0/87 (0%)
Leukaemic infiltration	1/59 (1.7%)		0/87 (0%)
Nervous system disorders
Aphasia	1/59 (1.7%)		0/87 (0%)
Cerebral infarction	2/59 (3.4%)		1/87 (1.1%)
Cerebrovascular accident	1/59 (1.7%)		0/87 (0%)
Convulsion	0/59 (0%)		2/87 (2.3%)
Haemorrhagic transformation stroke	1/59 (1.7%)		0/87 (0%)
Headache	0/59 (0%)		1/87 (1.1%)
Hemiparesis	1/59 (1.7%)		0/87 (0%)
Transient ischaemic attack	0/59 (0%)		1/87 (1.1%)
Psychiatric disorders
Abnormal behaviour	1/59 (1.7%)		0/87 (0%)
Aggression	1/59 (1.7%)		0/87 (0%)
Agitation	1/59 (1.7%)		0/87 (0%)
Confusional state	1/59 (1.7%)		0/87 (0%)
Hallucination	1/59 (1.7%)		0/87 (0%)
Renal and urinary disorders
Renal failure	1/59 (1.7%)		0/87 (0%)
Renal failure acute	6/59 (10.2%)		2/87 (2.3%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/59 (1.7%)		0/87 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/59 (1.7%)		0/87 (0%)
Acute respiratory failure	0/59 (0%)		3/87 (3.4%)
Dyspnoea	0/59 (0%)		1/87 (1.1%)
Haemoptysis	1/59 (1.7%)		1/87 (1.1%)
Hypercapnia	0/59 (0%)		1/87 (1.1%)
Hypoxia	1/59 (1.7%)		0/87 (0%)
Pleural effusion	0/59 (0%)		1/87 (1.1%)
Pneumonia aspiration	1/59 (1.7%)		1/87 (1.1%)
Pulmonary alveolar haemorrhage	1/59 (1.7%)		0/87 (0%)
Pulmonary embolism	0/59 (0%)		1/87 (1.1%)
Pulmonary infarction	1/59 (1.7%)		0/87 (0%)
Pulmonary oedema	0/59 (0%)		1/87 (1.1%)
Respiratory failure	4/59 (6.8%)		1/87 (1.1%)
Sinus disorder	0/59 (0%)		1/87 (1.1%)
Tachypnoea	0/59 (0%)		1/87 (1.1%)
Wheezing	0/59 (0%)		1/87 (1.1%)
Vascular disorders
Arteritis	1/59 (1.7%)		0/87 (0%)
Deep vein thrombosis	1/59 (1.7%)		1/87 (1.1%)
Hypotension	2/59 (3.4%)		0/87 (0%)
Other (Not Including Serious) Adverse Events
	Renally Impaired (RI)		Not Renally Impaired (NRI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/59 (91.5%)		68/87 (78.2%)
Blood and lymphatic system disorders
Febrile neutropenia	4/59 (6.8%)		2/87 (2.3%)
Neutropenia	6/59 (10.2%)		2/87 (2.3%)
Cardiac disorders
Atrial fibrillation	4/59 (6.8%)		1/87 (1.1%)
Sinus tachycardia	3/59 (5.1%)		2/87 (2.3%)
Tachycardia	4/59 (6.8%)		4/87 (4.6%)
Gastrointestinal disorders
Abdominal pain	7/59 (11.9%)		4/87 (4.6%)
Abdominal pain upper	1/59 (1.7%)		5/87 (5.7%)
Constipation	5/59 (8.5%)		10/87 (11.5%)
Diarrhoea	16/59 (27.1%)		10/87 (11.5%)
Haematochezia	3/59 (5.1%)		1/87 (1.1%)
Nausea	19/59 (32.2%)		14/87 (16.1%)
Stomatitis	3/59 (5.1%)		0/87 (0%)
Vomiting	16/59 (27.1%)		17/87 (19.5%)
General disorders
Asthenia	1/59 (1.7%)		7/87 (8%)
Chills	5/59 (8.5%)		3/87 (3.4%)
Fatigue	4/59 (6.8%)		2/87 (2.3%)
Oedema peripheral	8/59 (13.6%)		8/87 (9.2%)
Pain	3/59 (5.1%)		2/87 (2.3%)
Pyrexia	9/59 (15.3%)		15/87 (17.2%)
Infections and infestations
Clostridial infection	3/59 (5.1%)		0/87 (0%)
Clostridium difficile colitis	3/59 (5.1%)		1/87 (1.1%)
Herpes zoster	1/59 (1.7%)		5/87 (5.7%)
Upper respiratory tract infection	5/59 (8.5%)		6/87 (6.9%)
Urinary tract infection	7/59 (11.9%)		2/87 (2.3%)
Investigations
Blood alkaline phosphatase increased	3/59 (5.1%)		2/87 (2.3%)
Gamma-glutamyltransferase increased	4/59 (6.8%)		6/87 (6.9%)
Metabolism and nutrition disorders
Decreased appetite	4/59 (6.8%)		6/87 (6.9%)
Hyperglycaemia	3/59 (5.1%)		4/87 (4.6%)
Hyperkalaemia	7/59 (11.9%)		4/87 (4.6%)
Hypernatraemia	3/59 (5.1%)		1/87 (1.1%)
Hypocalcaemia	3/59 (5.1%)		3/87 (3.4%)
Hypokalaemia	6/59 (10.2%)		6/87 (6.9%)
Hypomagnesaemia	2/59 (3.4%)		7/87 (8%)
Hypophosphataemia	3/59 (5.1%)		0/87 (0%)
Musculoskeletal and connective tissue disorders
Back pain	6/59 (10.2%)		8/87 (9.2%)
Musculoskeletal chest pain	3/59 (5.1%)		5/87 (5.7%)
Myalgia	3/59 (5.1%)		2/87 (2.3%)
Pain in extremity	4/59 (6.8%)		3/87 (3.4%)
Nervous system disorders
Dizziness	3/59 (5.1%)		5/87 (5.7%)
Headache	11/59 (18.6%)		14/87 (16.1%)
Psychiatric disorders
Confusional state	7/59 (11.9%)		2/87 (2.3%)
Insomnia	5/59 (8.5%)		8/87 (9.2%)
Renal and urinary disorders
Oliguria	3/59 (5.1%)		0/87 (0%)
Renal impairment	3/59 (5.1%)		1/87 (1.1%)
Respiratory, thoracic and mediastinal disorders
Cough	3/59 (5.1%)		12/87 (13.8%)
Dyspnoea	6/59 (10.2%)		7/87 (8%)
Epistaxis	2/59 (3.4%)		5/87 (5.7%)
Haemoptysis	3/59 (5.1%)		1/87 (1.1%)
Oropharyngeal pain	4/59 (6.8%)		2/87 (2.3%)
Skin and subcutaneous tissue disorders
Pruritus	2/59 (3.4%)		7/87 (8%)
Vascular disorders
Hypertension	3/59 (5.1%)		5/87 (5.7%)
Hypotension	5/59 (8.5%)		5/87 (5.7%)

Limitations/Caveats

Enrollment in the clinical study was suspended in January 2009 pending further characterization of newly identified impurities. After successful study completion resumption of enrollment started in April 2011 for the 9766-CL-0103/WSA-CS-003 study.

More Information

Certain Agreements

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

Publication. At least sixty (60) days prior to submitting or presenting a manuscript or other materials relating to the Study to a publisher, reviewer, or other outside persons, the Site shall provide to Sponsor a copy of all such manuscripts and materials , and allow Sponsor sixty (60) days to review and comment on them.