Isavuconazole in the Treatment of Renally Impaired Asperg... | NCT00634049

ID	Type	Description	Link
WSA-CS-003	Other Identifier	Basilea Protocol ID
2006-005003-33	EudraCT Number

Status Module

Name	Class
Basilea Pharmaceutica International Ltd	INDUSTRY

Description Module

Label	Type	Description	Intervention Names
Isavuconazole	Experimental	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

Name	Type	Description	Arm Group Labels	Other Names
isavuconazole	Drug	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

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Measure	Description	Time Frame
Crude Success Rate of Clinical Response to Treatment Evaluated by the Data Review Committee (DRC) at Day 42, 84 and EOT	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.

Eligibility Module

Eligibility Criteria

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.

•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.

•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.

• 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

Name	Affiliation	Role
Medical Director	Astellas Pharma Global Development	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35294	United States
City Of Hope National Medical Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37185921	Derived	Hamed K, Engelhardt M, Kovanda LL, Huang JJ, Yan J, Aram JA. Post-hoc analysis of the safety and efficacy of isavuconazole in older patients with invasive fungal disease from the VITAL and SECURE studies. Sci Rep. 2023 Apr 25;13(1):6730. doi: 10.1038/s41598-023-31788-1.
27185799	Derived	Kovanda LL, Desai AV, Lu Q, Townsend RW, Akhtar S, Bonate P, Hope WW. Isavuconazole Population Pharmacokinetic Analysis Using Nonparametric Estimation in Patients with Invasive Fungal Disease (Results from the VITAL Study). Antimicrob Agents Chemother. 2016 Jul 22;60(8):4568-76. doi: 10.1128/AAC.00514-16. Print 2016 Aug.

Label	URL
Link to results on Astellas Clinical Study Results website	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Isavuconazole	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00049.9± 16.78

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00046
Male	BG000100

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000
Asian	BG00024

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG00022

Not Hispanic or Latino

Title	Measurements
	BG000

Region of Enrollment

Number

participants

Title

Denominators

Categories

Brazil

Title	Measurements
	BG00020

India

Title	Measurements
	BG000

Therapy status

Number

participants

Title

Denominators

Categories

Primary Therapy

Title	Measurements
	BG00093

Refractory

Title	Measurements
	BG000

Hematologic malignancy

Number

participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG00063

Title	Measurements
	BG000

Allogeneic Bone Marrow Transplant (BMT)/Hematopoietic Stem Cell Transplant (HSCT)

Allogeneic BMT/HSCT status was defined as yes for participants who noted allogeneic for type of transplant and bone marrow cells for type of cells on the primary underlying disease or condition electronic case report form (eCRF). Otherwise, allogeneic BMT/HSCT status equaled no.

Number

participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG00026

Title	Measurements

Uncontrolled malignancy

Uncontrolled malignancy status was defined as yes for participants who noted a malignancy for diagnosis and new diagnosis/active disease or relapse for present status on the primary underlying disease or condition eCRF. Otherwise, uncontrolled malignancy status equaled no.

Number

participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG00046

Title	Measurements

Neutropenic

Baseline neutropenic status was defined as yes for patients who noted recently resolved or ongoing neutropenia among the list of host factors on the categorization of IFD eCRF. Baseline neutropenic status was defined as no for patients who completed the categorization of IFD eCRF and did not meet the criterion in the previous sentence. Otherwise, baseline neutropenic status was missing.

Number

participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG00038

Title	Measurements

Corticosteroid use

Corticosteroid use was defined as yes for participants who were administered corticosteroids for 21 days out of 28 days leading up to first administration of study drug. Otherwise, corticosteroid use equaled no.

Number

participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG00035

Title	Measurements
	BG000

T-cell immunosuppressant use

T-cell immunosuppressant use was defined as yes for patients who noted treatment with other recognized T-cell immunosuppressants among the list of host factors on the categorization of IFD eCRF. Along with the investigators' assessment, participants who took certain prior medications could have been considered based on the medical evaluation. T-cell immunosuppressant use was defined as no for participants who completed the categorization of IFD eCRF and did not meet the criterion in the previous sentences. Otherwise, T-cell immunosuppressant use was missing.

Number

participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG00061

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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.

Modified Intent-To-Treat population (mITT)

Posted

Number

percentage of participants

Day 42, 84 and End of Treatment (EOT [Day 180])

ID	Title	Description
OG000	mITT - Aspergillus [Renally Impaired]	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).
OG001	mITT - Aspergillus [Not Renally Impaired]	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).
OG002	mITT - Mucorales (Primary Therapy)	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.
OG003	mITT - Mucorales (Refractory)	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)
OG004	mITT - Mucorales (Intolerant)	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).
OG005	mITT- Other Filamentous Fungi	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).
OG006	mITT- Other Mould Species Only	Other Mould Species mITT population consisted of 7 participants who had proven or probable IFD as determined by the DRC caused by mould species.
OG007	mITT- Other Dimorphic Fungi	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).
OG008	mITT- Other Non-Candida Yeast	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).
OG009	mITT-Other Mixed Infection	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.

Units	Counts
Participants	OG00020 OG0014 OG00221 OG003

Title

Denominators

Categories

Day 42- Success Rate

Title	Measurements
	OG00025.0 OG00150.0 OG00214.3 OG003

Secondary

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

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.

Modified Intent-To-Treat population (mITT)

Posted

Number

percentage of participants

Day 42, 84 and End of Treatment (EOT [Day 180])

ID	Title	Description
OG000	mITT - Aspergillus [Renally Impaired]	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).
OG001	mITT - Aspergillus [Not Renally Impaired]

Secondary

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

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.

Modified Intent-To-Treat population (mITT)

Posted

Number

percentage of participants

Day 42, 84 and End of Treatment (EOT [Day 180])

ID	Title	Description
OG000	mITT - Aspergillus [Renally Impaired]	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).
OG001	mITT - Aspergillus [Not Renally Impaired]	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).

Secondary

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

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.

Modified Intent-To-Treat population (mITT)

Posted

Number

percentage of participants

Day 42, 84 and End of Treatment (EOT [Day 180])

ID	Title	Description
OG000	mITT - Aspergillus [Renally Impaired]	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).

Secondary

Crude Success Rate of Clinical Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT

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.

Modified Intent-To-Treat population (mITT)

Posted

Number

percentage of participants

Day 42, Day 84 and End of Treatment (EOT [Day 180])

ID	Title	Description
OG000	mITT - Aspergillus [Renally Impaired]	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).
OG001	mITT - Aspergillus [Not Renally Impaired]

Secondary

Crude Success Rate of Mycological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT

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.

Modified Intent-To-Treat population (mITT)

Posted

Number

percentage of participants

Day 42, Day 84 and End of Treatment (EOT [Day 180])

ID	Title	Description
OG000	mITT - Aspergillus [Renally Impaired]	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).
OG001	mITT - Aspergillus [Not Renally Impaired]	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).

Secondary

Crude Success Rate of Radiological Response to Treatment Evaluated by the Investigator at Day 42, Day 84 and EOT

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.

Modified Intent-To-Treat population (mITT)

Posted

Number

percentage of participants

Day 42, Day 84 and End of Treatment (EOT [Day 180])

ID	Title	Description
OG000	mITT - Aspergillus [Renally Impaired]	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).
OG001	mITT - Aspergillus [Not Renally Impaired]

Secondary

All-cause Mortality Through Day 42 and Day 84

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.

Intent-To-Treat population (ITT)

Posted

Number

percentage of participants

Baseline to End of Treatment (EOT [Day 180])

ID	Title	Description
OG000	Renally Impaired	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).
OG001	Not Renally Impaired	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).

Secondary

Safety - Overall Number of TEAEs

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.

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

Posted

Number

participants

From the first study drug administration until 28 days after the last dose of study drug

ID	Title	Description
OG000	Isavuconazole	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.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Atrial fibrillation	Cardiac disorders	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0010 affected87 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Cardiac failure acute	Cardiac disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Electromechanical dissociation	Cardiac disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Retinal artery occlusion	Eye disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Retinal haemorrhage	Eye disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Vitreous haemorrhage	Eye disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0013 affected87 at risk
Colitis	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Constipation	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Dysphagia	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0010 affected87 at risk
Localised intraabdominal fluid collection	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Nausea	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0012 affected87 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Pancreatitis relapsing	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Vomiting	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0014 affected87 at risk
Death	General disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0012 affected87 at risk
General physical health deterioration	General disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Multi-organ failure	General disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Non-cardiac chest pain	General disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Oedema peripheral	General disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Pyrexia	General disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Acute hepatic failure	Hepatobiliary disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Cholangiolitis	Hepatobiliary disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Liver disorder	Hepatobiliary disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Acute graft versus host disease	Immune system disorders	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0010 affected87 at risk
Graft versus host disease	Immune system disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Lung transplant rejection	Immune system disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Abdominal abscess	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Appendicitis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Aspergillosis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0012 affected87 at risk
BK virus infection	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Bacteraemia	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0010 affected87 at risk
Bacterial sepsis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Brain abscess	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Bronchiectasis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Bronchiolitis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Catheter site infection	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Cytomegalovirus enteritis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Empyema	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Enterococcal bacteraemia	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Escherichia bacteraemia	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Escherichia sepsis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Fungal infection	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Fungal sepsis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Gastroenteritis norovirus	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Gastroenteritis viral	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Herpes zoster	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0012 affected87 at risk
Influenza	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Lung infection	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Lung infection pseudomonal	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Mucormycosis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0012 affected87 at risk
Pneumocystis jiroveci pneumonia	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Pneumonia	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0016 affected87 at risk
Pneumonia bacterial	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0012 affected87 at risk
Pneumonia blastomyces	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Pneumonia fungal	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0012 affected87 at risk
Pneumonia influenzal	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Pneumonia primary atypical	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Pseudomonal sepsis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0012 affected87 at risk
Pseudomonas bronchitis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Sepsis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0011 affected87 at risk
Septic shock	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0006 affected59 at risk EG0010 affected87 at risk
Sinusitis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Sinusitis fungal	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Staphylococcal infection	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Streptococcal bacteraemia	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Subcutaneous abscess	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Urinary tract infection	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Urosepsis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Viral diarrhoea	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Zygomycosis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0012 affected87 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0011 affected87 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0010 affected87 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Systemic lupus erythematosus	Musculoskeletal and connective tissue disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Acute lymphocytic leukaemia recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0010 affected87 at risk
Acute myeloid leukaemia recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0012 affected87 at risk
Chronic lymphocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0012 affected87 at risk
Aphasia	Nervous system disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Cerebral infarction	Nervous system disorders	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0011 affected87 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Convulsion	Nervous system disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0012 affected87 at risk
Haemorrhagic transformation stroke	Nervous system disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Headache	Nervous system disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Hemiparesis	Nervous system disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Leukaemia recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Abnormal behaviour	Psychiatric disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Aggression	Psychiatric disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Agitation	Psychiatric disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Confusional state	Psychiatric disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Hallucination	Psychiatric disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Renal failure	Renal and urinary disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Renal failure acute	Renal and urinary disorders	MedDRA version 12.1	Systematic Assessment	EG0006 affected59 at risk EG0012 affected87 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0013 affected87 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Hypercapnia	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Pulmonary alveolar haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Pulmonary infarction	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0004 affected59 at risk EG0011 affected87 at risk
Sinus disorder	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected87 at risk
Arteritis	Vascular disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk
Deep vein thrombosis	Vascular disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0011 affected87 at risk
Hypotension	Vascular disorders	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0010 affected87 at risk
Leukaemic infiltration	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected87 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 12.1	Systematic Assessment	EG0004 affected59 at risk EG0012 affected87 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA version 12.1	Systematic Assessment	EG0006 affected59 at risk EG0012 affected87 at risk
Atrial fibrillation	Cardiac disorders	MedDRA version 12.1	Systematic Assessment	EG0004 affected59 at risk EG0011 affected87 at risk
Sinus tachycardia	Cardiac disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0012 affected87 at risk
Tachycardia	Cardiac disorders	MedDRA version 12.1	Systematic Assessment	EG0004 affected59 at risk EG0014 affected87 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0007 affected59 at risk EG0014 affected87 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0015 affected87 at risk
Constipation	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0005 affected59 at risk EG00110 affected87 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG00016 affected59 at risk EG00110 affected87 at risk
Haematochezia	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0011 affected87 at risk
Nausea	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG00019 affected59 at risk EG00114 affected87 at risk
Stomatitis	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0010 affected87 at risk
Vomiting	Gastrointestinal disorders	MedDRA version 12.1	Systematic Assessment	EG00016 affected59 at risk EG00117 affected87 at risk
Asthenia	General disorders	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0017 affected87 at risk
Chills	General disorders	MedDRA version 12.1	Systematic Assessment	EG0005 affected59 at risk EG0013 affected87 at risk
Fatigue	General disorders	MedDRA version 12.1	Systematic Assessment	EG0004 affected59 at risk EG0012 affected87 at risk
Oedema peripheral	General disorders	MedDRA version 12.1	Systematic Assessment	EG0008 affected59 at risk EG0018 affected87 at risk
Pain	General disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0012 affected87 at risk
Pyrexia	General disorders	MedDRA version 12.1	Systematic Assessment	EG0009 affected59 at risk EG00115 affected87 at risk
Clostridial infection	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0010 affected87 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0011 affected87 at risk
Herpes zoster	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0001 affected59 at risk EG0015 affected87 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0005 affected59 at risk EG0016 affected87 at risk
Urinary tract infection	Infections and infestations	MedDRA version 12.1	Systematic Assessment	EG0007 affected59 at risk EG0012 affected87 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0012 affected87 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA version 12.1	Systematic Assessment	EG0004 affected59 at risk EG0016 affected87 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0004 affected59 at risk EG0016 affected87 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0014 affected87 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0007 affected59 at risk EG0014 affected87 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0011 affected87 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0013 affected87 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0006 affected59 at risk EG0016 affected87 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0017 affected87 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0010 affected87 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 12.1	Systematic Assessment	EG0006 affected59 at risk EG0018 affected87 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0015 affected87 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0012 affected87 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 12.1	Systematic Assessment	EG0004 affected59 at risk EG0013 affected87 at risk
Dizziness	Nervous system disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0015 affected87 at risk
Headache	Nervous system disorders	MedDRA version 12.1	Systematic Assessment	EG00011 affected59 at risk EG00114 affected87 at risk
Confusional state	Psychiatric disorders	MedDRA version 12.1	Systematic Assessment	EG0007 affected59 at risk EG0012 affected87 at risk
Insomnia	Psychiatric disorders	MedDRA version 12.1	Systematic Assessment	EG0005 affected59 at risk EG0018 affected87 at risk
Oliguria	Renal and urinary disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0010 affected87 at risk
Renal impairment	Renal and urinary disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0011 affected87 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG00112 affected87 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0006 affected59 at risk EG0017 affected87 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0015 affected87 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0011 affected87 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA version 12.1	Systematic Assessment	EG0004 affected59 at risk EG0012 affected87 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA version 12.1	Systematic Assessment	EG0002 affected59 at risk EG0017 affected87 at risk
Hypertension	Vascular disorders	MedDRA version 12.1	Systematic Assessment	EG0003 affected59 at risk EG0015 affected87 at risk
Hypotension	Vascular disorders	MedDRA version 12.1	Systematic Assessment	EG0005 affected59 at risk EG0015 affected87 at risk

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Renally Impaired (RI)	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.			43	59	54	59
EG001	Not Renally Impaired (NRI)	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.			46	87	68	87

ID	Term
D009181	Mycoses
D001423	Bacterial Infections and Mycoses
D007239	Infections