An Open-Label Study of JZP-458 (RC-P) in Patients With Ac... | NCT04145531

ID	Type	Description	Link
AALL1931	Other Identifier	Children's Oncology Group

Name	Class
Children's Oncology Group	NETWORK

Label	Type	Description	Intervention Names
JZP-458	Experimental	Part A (IM JZP-458) of the study will have 2 IM cohorts: Cohort 1: a JZP-458 repeat dose/confirmatory cohort; a final IM JZP-458 dose level will be selected, and Cohort 2: an expansion cohort to confirm the efficacy and safety of the final IM JZP-458 dose level and schedule Part B (IV JZP-458 Dose Confirmation) will be conducted to define the optimal dose of the IV administration of JZP-458 for further study in ALL/LBL patients as a repeated dose. Additional courses of JZP-458 (IM or IV depending on patient's allocation at study enrollment) will be administered based on each patient's original treatment plan for as long as the patient derives clinical benefit.	Drug: IM JZP-458 Drug: IV JZP-458

Name	Type	Description	Arm Group Labels	Other Names
IM JZP-458	Drug	IM JZP-458 will be administered in Part A, Cohorts 1 & 2	JZP-458

Measure	Description	Time Frame
Response Rate During the First Course of JZP-458 Administration	The response rate was defined as the number (proportion) of patients with the last 72-hour nadir serum asparaginase activity (NSAA) level ≥ 0.1 IU/mL during the first course of IM JZP-458. Blood samples were collected for serum asparaginase activity level determination.	Baseline up to 2 weeks
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered related to study drug. AEs were classified by the Investigator using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.	Date of written informed consent up to 30 days after last dose of last course, up to approximately 2 years 7 months

Measure	Description	Time Frame
Number of Participants With Last 48-hour NSAA Level ≥ 0.1 IU/mL During The First Course (6 Doses) of JZP-458 Administration	Blood samples were collected for serum asparaginase activity level determination.	Baseline up to 2 weeks
Number of Participants With Last NSAA Levels ≥ 0.4 IU/mL During The First Course (6 Doses) of JZP-458 Administration

Facility	Status	City	State	ZIP	Country	Contacts
Children's of Alabama		Birmingham	Alabama	35233	United States
Phoenix Children's Hospital

PubMed Identifier	Type	Citation	Retractions
36108304	Result	Maese L, Loh ML, Choi MR, Lin T, Aoki E, Zanette M, Agarwal S, Iannone R, Silverman JA, Silverman LB, Raetz EA, Rau RE. Recombinant Erwinia asparaginase (JZP458) in acute lymphoblastic leukemia: results from the phase 2/3 AALL1931 study. Blood. 2023 Feb 16;141(7):704-712. doi: 10.1182/blood.2022016923.
39454281	Derived

ID	Title	Description
FG000	Part A: JZP-458 IM 25 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks based on available data from the Phase 1 (JZP458-101) healthy volunteer study.
FG001	Part A: JZP-458 IM 37.5 mg/m^2 (MWF)

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 3, 2020	Jul 11, 2023

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

Response Rate During the First Course of JZP-458 Administration

The response rate was defined as the number (proportion) of patients with the last 72-hour nadir serum asparaginase activity (NSAA) level ≥ 0.1 IU/mL during the first course of IM JZP-458. Blood samples were collected for serum asparaginase activity level determination.

Response rates were assessed in the Efficacy Analysis Set in participants with available data.

Posted

Count of Participants

Participants

Baseline up to 2 weeks

ID	Title	Description
OG000	Part A: JZP-458 IM 25 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks based on available data from the Phase 1 (JZP458-101) healthy volunteer study.
OG001	Part A: JZP-458 IM 37.5 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 37.5 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
OG002	Part A: JZP-458 IM 25 (MW)/50 mg/m^2 (F)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on Mondays and Wednesdays and 50 mg/m^2 on Fridays on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
OG003	Part B: JZP-458 IV 25 (MW)/50 mg/m^2 (F)	Participants who received an intravenous (IV) dose of JZP-458 25 mg/m^2 on Mondays and Wednesdays and 50 mg/m^2 on Fridays on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.

Units	Counts
Participants	OG00028 OG00177 OG00249 OG003

Title

Denominators

Categories

Title	Measurements
	OG00018 OG00170 OG00244 OG003

Primary

Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered related to study drug. AEs were classified by the Investigator using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Safety events were assessed in the Safety Analysis Set.

Posted

Count of Participants

Participants

Date of written informed consent up to 30 days after last dose of last course, up to approximately 2 years 7 months

ID	Title	Description
OG000	Part A: JZP-458 IM 25 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks based on available data from the Phase 1 (JZP458-101) healthy volunteer study.
OG001	Part A: JZP-458 IM 37.5 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 37.5 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
OG002	Part A: JZP-458 IM 25 (MW)/50 mg/m^2 (F)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on Mondays and Wednesdays and 50 mg/m^2 on Fridays on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.

Secondary

Number of Participants With Last 48-hour NSAA Level ≥ 0.1 IU/mL During The First Course (6 Doses) of JZP-458 Administration

Blood samples were collected for serum asparaginase activity level determination.

Nadir serum asparaginase activity levels were assessed in the Efficacy Analysis Set.

Posted

Count of Participants

Participants

Baseline up to 2 weeks

ID	Title	Description
OG000	Part A: JZP-458 IM 25 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks based on available data from the Phase 1 (JZP458-101) healthy volunteer study.
OG001	Part A: JZP-458 IM 37.5 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 37.5 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
OG002	Part A: JZP-458 IM 25 (MW)/50 mg/m^2 (F)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on Mondays and Wednesdays and 50 mg/m^2 on Fridays on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
OG003

Secondary

Number of Participants With Last NSAA Levels ≥ 0.4 IU/mL During The First Course (6 Doses) of JZP-458 Administration

Blood samples were collected for serum asparaginase activity level determination.

Nadir serum asparaginase activity levels were assessed in the Efficacy Analysis Set in participants with available data.

Posted

Count of Participants

Participants

Baseline up to 2 weeks

ID	Title	Description
OG000	Part A: JZP-458 IM 25 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks based on available data from the Phase 1 (JZP458-101) healthy volunteer study.
OG001	Part A: JZP-458 IM 37.5 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 37.5 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
OG002	Part A: JZP-458 IM 25 (MW)/50 mg/m^2 (F)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on Mondays and Wednesdays and 50 mg/m^2 on Fridays on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
OG003

Secondary

Mean Serum Asparaginase Activity Levels in First Course of JZP-458 Administration

Serum asparaginase levels serve as a surrogate marker for asparagine depletion. Mean serum asparaginase activity levels in Course 1 are reported.

Serum asparaginase activity levels were assessed in participants with available data in the Efficacy Analysis Set.

Posted

Mean

95% Confidence Interval

IU/mL

Up to 2 weeks (6 doses)

ID	Title	Description
OG000	Part A: JZP-458 IM 25 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks based on available data from the Phase 1 (JZP458-101) healthy volunteer study.
OG001	Part A: JZP-458 IM 37.5 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 37.5 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
OG002	Part A: JZP-458 IM 25 (MW)/50 mg/m^2 (F)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on Mondays and Wednesdays and 50 mg/m^2 on Fridays on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.

Secondary

Number of Participants Who Are Anti-drug Antibody Positive or Negative Against JZP-458

Blood samples were collected for immunogenicity analysis. Anti-drug antibody positive (ADA+) participants were those with a positive result on the first test and also a positive result on the confirmatory test. Anti-drug antibody negative (ADA-) participants had a negative result on the first test.

Immunogenicity was assessed in the Safety Analysis Set.

Posted

Count of Participants

Participants

Baseline up to 30 days (ADA- samples) after last dose of last course and up to 6 months (ADA+ samples) after last dose of last course, up to approximately 2 years 7 months

ID	Title	Description
OG000	Part A: JZP-458 IM 25 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks based on available data from the Phase 1 (JZP458-101) healthy volunteer study.
OG001	Part A: JZP-458 IM 37.5 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 37.5 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
OG002	Part A: JZP-458 IM 25 (MW)/50 mg/m^2 (F)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on Mondays and Wednesdays and 50 mg/m^2 on Fridays on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0009 affected33 at risk EG00124 affected83 at risk EG00220 affected51 at risk EG00314 affected61 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0013 affected83 at risk EG0021 affected51 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0020 affected51 at risk EG003
Methaemoglobinaemia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0021 affected51 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0014 affected83 at risk EG0024 affected51 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0018 affected83 at risk EG0022 affected51 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0016 affected83 at risk EG0021 affected51 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0013 affected83 at risk EG0023 affected51 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0014 affected83 at risk EG0021 affected51 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0020 affected51 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Anal inflammation	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Oesophageal fistula	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Pancreatic pseudocyst	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Pyrexia	General disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0018 affected83 at risk EG0028 affected51 at risk EG003
Catheter site haemorrhage	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Chills	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Infusion site extravasation	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Multiple organ dysfunction syndrome	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0014 affected83 at risk EG0022 affected51 at risk EG003
Anaphylactic reaction	Immune system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0013 affected83 at risk EG0020 affected51 at risk EG003
Cytokine release syndrome	Immune system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Sepsis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0015 affected83 at risk EG0026 affected51 at risk EG003
Enterocolitis infectious	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0023 affected51 at risk EG003
Corona virus infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected83 at risk EG0022 affected51 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0022 affected51 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0020 affected51 at risk EG003
Pneumonia	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Skin infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Soft tissue infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Anal abscess	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Anorectal infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Cellulitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Citrobacter infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Escherichia bacteraemia	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Gastroenteritis norovirus	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Groin abscess	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Herpes simplex	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Necrotising fasciitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Otitis media	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Parainfluenzae virus infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Urinary tract infection bacterial	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Wound infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected83 at risk EG0023 affected51 at risk EG003
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Anaphylactic transfusion reaction	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Transfusion reaction	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Wound complication	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Platelet count decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Weight decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0022 affected51 at risk EG003
Amylase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Blood creatine increase	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Blood creatinine increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Lipase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Shigella test positive	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
White blood cell count decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Blood culture positive	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Drug clearance decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0017 affected83 at risk EG0025 affected51 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0022 affected51 at risk EG003
Hyperammonaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0020 affected51 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Acidosis	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0022 affected51 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Histiocytic sarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
T-cell lymphoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Neurotoxicity	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0022 affected51 at risk EG003
Dysarthria	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0022 affected51 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0020 affected51 at risk EG003
Hemiparesis	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Seizure	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0020 affected51 at risk EG003
Cerebrospinal fluid leakage	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Facial paralysis	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Headache	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Leukoencephalopathy	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Posterior reversible encephalopathy syndrome	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Presyncope	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Superior sagittal sinus thrombosis	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Syncope	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Hyperammonaemic encephalopathy	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Agitation	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Irritability	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Personality change	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0014 affected83 at risk EG0023 affected51 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Nephropathy toxic	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0020 affected51 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0020 affected51 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Pharyngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Hypotension	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0022 affected51 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG00013 affected33 at risk EG00147 affected83 at risk EG00228 affected51 at risk EG00322 affected61 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0015 affected83 at risk EG0022 affected51 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected83 at risk EG0024 affected51 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected83 at risk EG0022 affected51 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected33 at risk EG00117 affected83 at risk EG0027 affected51 at risk EG003
Periorbital oedema	Eye disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Vision blurred	Eye disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0013 affected83 at risk EG0020 affected51 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected33 at risk EG00125 affected83 at risk EG00213 affected51 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0013 affected83 at risk EG0022 affected51 at risk EG003
Anal fissure	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected83 at risk EG0023 affected51 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0004 affected33 at risk EG00113 affected83 at risk EG0028 affected51 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0004 affected33 at risk EG00123 affected83 at risk EG00212 affected51 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0016 affected83 at risk EG0022 affected51 at risk EG003
Gastrooesophageal reflux	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0004 affected33 at risk EG0011 affected83 at risk EG0023 affected51 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0008 affected33 at risk EG00128 affected83 at risk EG00217 affected51 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0012 affected83 at risk EG0021 affected51 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0023 affected51 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0006 affected33 at risk EG00122 affected83 at risk EG00214 affected51 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG00012 affected33 at risk EG00139 affected83 at risk EG00215 affected51 at risk EG003
Asthenia	General disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Catheter site pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0014 affected83 at risk EG0025 affected51 at risk EG003
Catheter site rash	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0020 affected51 at risk EG003
Chills	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0016 affected83 at risk EG0022 affected51 at risk EG003
Fatigue	General disorders	MedDRA 22.1	Systematic Assessment	EG00010 affected33 at risk EG00132 affected83 at risk EG00213 affected51 at risk EG003
Injection site pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0014 affected83 at risk EG0023 affected51 at risk EG003
Injection site reaction	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected83 at risk EG0024 affected51 at risk EG003
Pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0004 affected33 at risk EG0016 affected83 at risk EG0020 affected51 at risk EG003
Pyrexia	General disorders	MedDRA 22.1	Systematic Assessment	EG0008 affected33 at risk EG00131 affected83 at risk EG00211 affected51 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0014 affected83 at risk EG0020 affected51 at risk EG003
Corona virus infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0015 affected83 at risk EG0021 affected51 at risk EG003
Enterocolitis infectious	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected83 at risk EG0021 affected51 at risk EG003
Paronychia	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected83 at risk EG0021 affected51 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0017 affected83 at risk EG0022 affected51 at risk EG003
Allergic transfusion reaction	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0016 affected83 at risk EG0024 affected51 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0012 affected83 at risk EG0021 affected51 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0004 affected33 at risk EG0018 affected83 at risk EG0028 affected51 at risk EG003
Activated partial thromboplastin time prolonged	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0017 affected83 at risk EG0023 affected51 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0006 affected33 at risk EG00129 affected83 at risk EG00210 affected51 at risk EG003
Antithrombin III decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0023 affected51 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0005 affected33 at risk EG00124 affected83 at risk EG0026 affected51 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0015 affected83 at risk EG0021 affected51 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG00112 affected83 at risk EG0024 affected51 at risk EG003
Blood cholesterol increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0004 affected33 at risk EG0013 affected83 at risk EG0021 affected51 at risk EG003
Blood creatinine increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0018 affected83 at risk EG0023 affected51 at risk EG003
Blood fibrinogen decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0013 affected83 at risk EG0020 affected51 at risk EG003
CD4 lymphocytes decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Haematocrit decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected83 at risk EG0022 affected51 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0008 affected33 at risk EG00121 affected83 at risk EG0029 affected51 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG00014 affected33 at risk EG00134 affected83 at risk EG00225 affected51 at risk EG003
Platelet count decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG00013 affected33 at risk EG00136 affected83 at risk EG00225 affected51 at risk EG003
Weight decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG00113 affected83 at risk EG0029 affected51 at risk EG003
Weight increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
White blood cell count decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG00012 affected33 at risk EG00125 affected83 at risk EG00212 affected51 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0007 affected33 at risk EG00128 affected83 at risk EG00215 affected51 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0019 affected83 at risk EG0023 affected51 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0007 affected33 at risk EG00114 affected83 at risk EG0027 affected51 at risk EG003
Hypermagnesemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0013 affected83 at risk EG0020 affected51 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0016 affected83 at risk EG0020 affected51 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0017 affected83 at risk EG0026 affected51 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0004 affected33 at risk EG00112 affected83 at risk EG0023 affected51 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0004 affected33 at risk EG0019 affected83 at risk EG0024 affected51 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0016 affected83 at risk EG0021 affected51 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG00114 affected83 at risk EG00211 affected51 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0015 affected83 at risk EG0021 affected51 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0017 affected83 at risk EG0024 affected51 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0015 affected83 at risk EG0022 affected51 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected33 at risk EG0019 affected83 at risk EG0024 affected51 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0009 affected33 at risk EG00122 affected83 at risk EG0027 affected51 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0017 affected83 at risk EG0022 affected51 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0012 affected83 at risk EG0022 affected51 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0011 affected83 at risk EG0023 affected51 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected83 at risk EG0020 affected51 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0013 affected83 at risk EG0022 affected51 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0008 affected33 at risk EG00118 affected83 at risk EG0029 affected51 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0013 affected83 at risk EG0021 affected51 at risk EG003
Dizziness	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0014 affected83 at risk EG0024 affected51 at risk EG003
Headache	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG00012 affected33 at risk EG00123 affected83 at risk EG00212 affected51 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0015 affected83 at risk EG0022 affected51 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0011 affected83 at risk EG0024 affected51 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0015 affected83 at risk EG0023 affected51 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0013 affected83 at risk EG0021 affected51 at risk EG003
Tremor	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0015 affected83 at risk EG0023 affected51 at risk EG003
Agitation	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0014 affected83 at risk EG0021 affected51 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0019 affected83 at risk EG0025 affected51 at risk EG003
Depression	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0015 affected83 at risk EG0022 affected51 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected33 at risk EG0018 affected83 at risk EG0023 affected51 at risk EG003
Irritability	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected33 at risk EG0018 affected83 at risk EG0022 affected51 at risk EG003
Mood swings	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected83 at risk EG0020 affected51 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0015 affected83 at risk EG0022 affected51 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected33 at risk EG00111 affected83 at risk EG0029 affected51 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0012 affected83 at risk EG0021 affected51 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0017 affected83 at risk EG0024 affected51 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0019 affected83 at risk EG0024 affected51 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG00110 affected83 at risk EG0026 affected51 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0004 affected33 at risk EG00110 affected83 at risk EG0024 affected51 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0004 affected33 at risk EG0014 affected83 at risk EG0022 affected51 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected83 at risk EG0024 affected51 at risk EG003
Dermatitis diaper	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0016 affected83 at risk EG0020 affected51 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0016 affected83 at risk EG0023 affected51 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0013 affected83 at risk EG0025 affected51 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0023 affected51 at risk EG003
Pruritis	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0016 affected83 at risk EG0023 affected51 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0015 affected83 at risk EG0023 affected51 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected33 at risk EG0018 affected83 at risk EG0023 affected51 at risk EG003
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected83 at risk EG0023 affected51 at risk EG003
Flushing	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0004 affected33 at risk EG0014 affected83 at risk EG0023 affected51 at risk EG003
Hypertension	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0016 affected83 at risk EG0028 affected51 at risk EG003
Hypotension	Vascular disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected33 at risk EG0016 affected83 at risk EG0022 affected51 at risk EG003

ID	Term
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma
D007938	Leukemia

ID	Term
D007945	Leukemia, Lymphoid
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Title	Description
BG000	Part A: JZP-458 IM 25 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks based on available data from the Phase 1 (JZP458-101) healthy volunteer study.
BG001	Part A: JZP-458 IM 37.5 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 37.5 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
BG002	Part A: JZP-458 IM 25 (MW)/50 mg/m^2 (F)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on Mondays and Wednesdays and 50 mg/m^2 on Fridays on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
BG003	Part B: JZP-458 IV 25 (MW)/50 mg/m^2 (F)	Participants who received an intravenous (IV) dose of JZP-458 25 mg/m^2 on Mondays and Wednesdays and 50 mg/m^2 on Fridays on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A: JZP-458 IM 25 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks based on available data from the Phase 1 (JZP458-101) healthy volunteer study.	1	33	20	33	31	33
EG001	Part A: JZP-458 IM 37.5 mg/m^2 (MWF)	Participants who received an intramuscular (IM) dose of JZP-458 37.5 mg/m^2 on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.	2	83	57	83	81	83
EG002	Part A: JZP-458 IM 25 (MW)/50 mg/m^2 (F)	Participants who received an intramuscular (IM) dose of JZP-458 25 mg/m^2 on Mondays and Wednesdays and 50 mg/m^2 on Fridays on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.	0	51	34	51	48	51
EG003	Part B: JZP-458 IV 25 (MW)/50 mg/m^2 (F)	Participants who received an intravenous (IV) dose of JZP-458 25 mg/m^2 on Mondays and Wednesdays and 50 mg/m^2 on Fridays on a Monday/Wednesday/Friday (MWF) schedule over 2 weeks.	0	61	40	61	56	61