Evaluate Safety and Efficacy of the Coadministration of I... | NCT03672292

ID	Type	Description	Link
2018-002565-18	EudraCT Number

Label	Type	Description	Intervention Names
SCY-078 plus Voriconazole	Experimental	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks	Drug: SCY-078 Drug: Voriconazole
Voriconazole mono-therapy	Placebo Comparator	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks	Drug: Voriconazole Other: Oral Placebo Tablets

Name	Type	Description	Arm Group Labels	Other Names
SCY-078	Drug	Oral tablets of SCY-078	SCY-078 plus Voriconazole	Ibrexafungerp

Measure	Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths	Number of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs and deaths.	Up to a maximum of 19 weeks

Measure	Description	Time Frame
Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC)	Number and percentage of participants with Complete Response or Partial Response as determined by the Data Review Committee (DRC). Complete Response: Survival and resolution of all attributable symptoms and signs of disease; plus, successful radiological outcome; plus, mycological eradication. Partial Response: Survival and partial resolution of attributable symptoms and signs of disease; plus, improvement (at least 25%) of radiological lesions; plus, mycological eradication.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject is a male or female adult ≥18 years of age on the day the study informed consent form (ICF) is signed.
Subject has a probable or proven IPA based on the protocol-specified criteria (Section 22.3) that requires antifungal treatment. Note: Subjects with possible IPA may enter the screening phase of the study but will only be randomized after meeting criteria for probable or proven IPA.
Subject has a result of a serum GMI from a sample obtained within the 96 hours preceding enrollment into the study (Baseline/Treatment Day 1).
Subject has a diagnosis of a hematological malignancy or a myelodysplastic syndrome or aplastic anemia or has undergone hematopoietic cell transplantation OR
Subject who either recently resolved or ongoing neutropenia (neutropenia defined as absolute neutrophil count < 0.5 x 10⁹/L [< 500/mm³] for > 10 days), temporally related to the onset of fungal disease OR
Subject who received treatment with other recognized T-cell immunosuppressants (such as cyclosporine, tacrolimus, monoclonal antibodies or nucleoside analogs) during the past 90 days including solid organ transplant patients OR
Subject with inherited severe immunodeficiency (e.g. chronic granulomatous disease, severe combined immunodeficiency)
Subject has not received more than 4 days (96 hours) of prior mold-active antifungal therapy for the treatment of the IPA episode in the 7 days preceding enrollment into the study (Baseline/Treatment Day 1). However, subjects who have received more than 4 days but less than 7 days of prior mold-active antifungal therapy for the treatment of the IPA episode in the 7 days preceding enrollment into the study may be enrolled but will require approval from the study medical monitor, who will evaluate each subject on a case-by-case basis.
Subject has an IPA episode that, in the investigator´s judgement, requires antifungal therapy and may be adequately treated with voriconazole (i.e., the IPA is not a breakthrough infection while receiving a mold-active azole antifungal [voriconazole, posaconazole, isavuconazole or itraconazole] that requires therapy with a non-azole antifungal agent).

Exclusion Criteria:

Subject has a fungal disease with central nervous system involvement suspected at Screening.
Subject is receiving, has received or anticipates to be receiving concomitant medications that are listed in the prohibited medication list (Appendix A in full protocol) within the specified washout periods.
Subject has a Karnofsky score <20.
Subject is expected to die from a non-infectious cause within 30 days from the day the study ICF is signed.
Subject is under mechanical ventilation.
Subject has abnormal liver test parameters: AST or ALT >5 x ULN and/or total bilirubin >2.5 x ULN.

Name	Affiliation	Role
David Angulo, MD	Scynexis, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Brigham Womens Hospital INF 75 Francis Street PBB-A4		Boston	Massachusetts	02115	United States
University of Michigan UH south F4005; 1500 E. Medical Center Drive SPC 5378

ID	Title	Description
FG000	SCY-078 Plus Voriconazole	Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 13, 2020	Apr 6, 2024

ID	Title	Description
BG000	SCY-078 Plus Voriconazole	Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks.
BG001	Voriconazole Mono-therapy	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given once a day (QD) from Day 3 onwards) maximum up to 13 weeks.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00010 BG00112 BG00222

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

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Drug-related Adverse Events (AEs), Discontinuations Due to AEs and Deaths

Number of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs and deaths.

Safety population including any participant treated with at least one dose of Voriconazole or SCY-078

Posted

Number

participants

Up to a maximum of 19 weeks

ID	Title	Description
OG000	SCY-078 Plus Voriconazole	Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks.
OG001	Voriconazole Mono-therapy	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given once a day (QD) from Day 3 onwards) maximum up to 13 weeks.

Units	Counts
Participants	OG00010 OG00112

Title

Denominators

Categories

Number of participants with treatment emergent adverse events

Title	Measurements
	OG00010 OG00111

Number of participants with treatment-related adverse events

Title	Measurements
	OG000

Secondary

Percentage of Participants With Complete Response or Partial Response as Determined by the Data Review Committee (DRC)

Number and percentage of participants with Complete Response or Partial Response as determined by the Data Review Committee (DRC). Complete Response: Survival and resolution of all attributable symptoms and signs of disease; plus, successful radiological outcome; plus, mycological eradication. Partial Response: Survival and partial resolution of attributable symptoms and signs of disease; plus, improvement (at least 25%) of radiological lesions; plus, mycological eradication.

Intent-to-Treat (ITT) Population including all randomized participants who received at least one dose of randomized study medication.

Posted

Count of Participants

Participants

At end of treatment (up to 13 weeks), day 42 and day 84

ID	Title	Description
OG000	SCY-078 Plus Voriconazole	Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks.
OG001	Voriconazole Mono-therapy	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given once a day (QD) from Day 3 onwards) maximum up to 13 weeks.

Secondary

Percentage of Participants Who Died (Any Cause)

Number and Percentage of participants who died (any cause)

Intent-to-Treat (ITT) Population including all randomized participants who received at least one dose of randomized study medication.

Posted

Count of Participants

Participants

At Day 42 and Day 84

ID	Title	Description
OG000	SCY-078 and Voriconazole	Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks.
OG001	Voriconazole Mono-Therapy	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given once a day (QD) from Day 3 onwards) maximum up to 13 weeks.

Secondary

Change in Serum Galactomannan Index (GMI)

Absolute change in serum GMI from from baseline to each time point (Weeks 1, 2, 4 and 6). Negative values indicate a reduction of GMI (i.e., improvement).

Participants who have a probable or proven invasive pulmonary aspergillosis at baseline, per DRC, with at least one positive serum GMI at baseline and at least one GMI value at Weeks 1, 2, 4 and/or 6.

Posted

Mean

Full Range

index

Weeks 1, 2, 4 and 6

ID	Title	Description
OG000	SCY-078 Plus Voriconazole	Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks.
OG001	Voriconazole Mono-therapy	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given once a day (QD) from Day 3 onwards) maximum up to 13 weeks.

Secondary

Percent of Participants With Changes in GMI

Percentage of participants with the following changes in GMI values from Baseline:

Fifty percent reduction or greater at Weeks 1, 2, 4 and 6
Twenty-five percent reduction or greater at Weeks 1, 2, 4 and 6
Any percent reduction at Weeks 1, 2, 4 and 6
Reduction equal to or greater than 0.25 at Weeks 1, 2, 4 and 6
Reduction to < 0.5 at Weeks 1, 2, 4 and 6

Modified Intent-to-treat (mITT) population including participants who have a probable or proven invasive pulmonary aspergillosis at baseline, per DRC, with at least one positive serum GMI at baseline.

Posted

Count of Participants

Participants

Weeks 1, 2, 4 and 6 from Baseline

ID	Title	Description
OG000	SCY-078 and Voriconazole	Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks.
OG001	Voriconazole Mono-Therapy	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given once a day (QD) from Day 3 onwards) maximum up to 13 weeks.

Secondary

Time to Achieve Serum GMI Change From Baseline

Time (days) to achieve the following changes in serum GMI from Baseline:

Fifty percent reduction
Twenty-five percent reduction
Any percent reduction
Reduction equal to or greater than 0.25

Intent-to-treat (ITT) population including participants who have a probable or proven invasive pulmonary aspergillosis at baseline, per DRC.

Posted

Median

95% Confidence Interval

Days

Up to a maximum of 19 weeks

ID	Title	Description
OG000	SCY-078 and Voriconazole	Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks.
OG001	Voriconazole Mono-Therapy	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given once a day (QD) from Day 3 onwards) maximum up to 13 weeks.

Secondary

Percentage of Participants With a Clinical, Mycological and Radiological Response by DRC

Percentage of participants with:

Clinical Response at EoT, Day 42 and Day 84, as determined by the DRC
Mycological Response at EoT, Day 42 and Day 84, as determined by the DRC
Radiological Response at EoT, Day 42 and Day 84, as determined by the DRC

Intent-to-Treat (ITT) Population including all randomized participants who received at least one dose of randomized study medication.

Posted

Count of Participants

Participants

End of Treatment (EoT), Day 42 and Day 84

ID	Title	Description
OG000	SCY-078 and Voriconazole	Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks.
OG001	Voriconazole Mono-Therapy	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given once a day (QD) from Day 3 onwards) maximum up to 13 weeks.

Secondary

Percentage of Participants With a Clinical, Mycological and Radiological Response.

Percentage of participants with:

Clinical Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator
Mycological Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator
Radiological Response at EoT, Day 42 and Day 84, as determined by the Principal Investigator

Intent-to-Treat (ITT) Population including all randomized participants who received at least one dose of randomized study medication.

Posted

Count of Participants

Participants

End of Treatment (EoT), Day 42 and Day 84

ID	Title	Description
OG000	SCY-078 and Voriconazole	Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks.
OG001	Voriconazole Mono-Therapy	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given once a day (QD) from Day 3 onwards) maximum up to 13 weeks.

Secondary

SCY-078 and Voriconazole Plasma Concentrations

Voriconazole and SCY-078 plasma concentrations (ng/mL)

Participants of study who provide a PK sample

Posted

Mean

Standard Deviation

nanograms per milliliter (ng/mL)

Treatment Days 7 and 14 (2-4 hrs post dose)

ID	Title	Description
OG000	SCY-078 and Voriconazole	Either intravenous (IV) voriconazole (loading dose of 6 milligram/kilogram (mg/kg) twice a day (BID) on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards) maximum up to 13 weeks.
OG001	Voriconazole Mono-Therapy	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards) PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given once a day (QD) from Day 3 onwards) maximum up to 13 weeks.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk
Haemolysis	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Thrombocytosis	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0012 affected12 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Tachycardia	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Dry eye	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Eye haematoma	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Eye haemorrhage	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Photopsia	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0012 affected12 at risk
Vision blurred	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk
Visual impairment	Eye disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Abdominal mass	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Anal fissure	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Angular cheilitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Colitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected10 at risk EG0010 affected12 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk
Ileus	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0005 affected10 at risk EG0011 affected12 at risk
Oral blood blister	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Terminal ileitis	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Toothache	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Vomiting	General disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected10 at risk EG0010 affected12 at risk
Chest pain	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk
Disease progression	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Oedema peripheral	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk
Pain	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Cholestasis	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0011 affected12 at risk
Acute graft versus host disease in liver	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Acute graft versus host disease in skin	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Graft versus host disease in gastrointestinal tract	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Graft versus host disease in liver	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Graft versus host disease in skin	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Haemophagocytic lymphohistiocytosis	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk
Heart transplant rejection	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Blastocystis infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Cellulitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Conjunctivitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Cytomegalovirus infection reactivation	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Enterobacter bacteraemia	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Enterococcal bacteraemia	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Enterococcal infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Enterococcal sepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Oral herpes	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected12 at risk
Staphylococcal infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Streptococcal sepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Urosepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Toxicity to Various Agents	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk
Blood bilirubin increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Drug level decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Ejection fraction decreased	Investigations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Hepatic enzyme increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Fluid retention	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Hypervolaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected12 at risk
Axillary mass	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk
Tendon disorder	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Anosmia	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Disturbance in attention	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Dizziness	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0011 affected12 at risk
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Restless legs syndrome	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Tremor	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Confusional state	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Delirium	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Hallucination	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk
Insomnia	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0012 affected12 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk
Urethral pain	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Urinary retention	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0012 affected12 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Sputum discoloured	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Stridor	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0011 affected12 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0013 affected12 at risk
Skin mass	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Hypotension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Blood cholesterol	Investigations	All Adverse Event	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk

ID	Term
D055744	Invasive Pulmonary Aspergillosis
D001228	Aspergillosis

ID	Term
D055732	Pulmonary Aspergillosis
D009181	Mycoses
D001423	Bacterial Infections and Mycoses
D007239	Infections
D000072742	Invasive Fungal Infections
D008172	Lung Diseases, Fungal
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	SCY-078 Plus Voriconazole	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks SCY-078: Oral tablets of SCY-078 Voriconazole: Voriconazole IV vials or oral tablets	3	10	6	10	10	10
EG001	Voriconazole Mono-therapy	Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks Voriconazole: Voriconazole IV vials or oral tablets Oral Placebo Tablets: Oral Placebo Tablets matching SCY-078	1	12	5	12	11	12

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	Adverse Event	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	All Adverse Event	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Colitis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Vomiting	Gastrointestinal disorders	All Adverse Event	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Disease progression	General disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Multiple organ dysfunction syndrome	General disorders	All Adverse Event	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Acute graft versus host disease in skin	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Graft versus host disease in gastrointestinal tract	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Haemophagocytic lymphohistiocytosis	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected10 at risk EG0010 affected12 at risk
Heart transplant rejection	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Enterobacter bacteraemia	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Enterococcal sepsis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Disturbance in attention	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected10 at risk EG0010 affected12 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected10 at risk EG0011 affected12 at risk