SGI-110 in Combination With Carboplatin in Ovarian Cancer | NCT01696032

Label	Type	Description	Intervention Names
SGI-110 + Carboplatin	Experimental	Stage 1 was a safety lead-in stage with a dose escalation design. Participants were evaluated with the combination of SGI-110 (guadecitabine) plus carboplatin (G+C), given as 28-day treatment cycles: guadecitabine administered subcutaneous (SC) daily on Days 1-5, at a starting dose of 45 mg/m2/day in Cohort 1, followed by carboplatin intravenous (IV) based on a targeted dose of area under the curve (AUC) 5 on Day 8. After dose limiting toxicities were noted, guadecitabine dose was reduced to 30 mg/m2/day for subsequent cycles for 4 participants. Cohort 2 received 30 mg/m2/day guadecitabine and carboplatin IV AUC 4.	Drug: SGI-110 Drug: Carboplatin
SGI-110 + Carboplatin or TC	Experimental	Stage 2 was an open-label, randomized, controlled trial. Eligible participants were randomly assigned in a 1:1 ratio to receive either (1) G+C combination treatment in 28-day cycles at 30 mg/m2 SC once daily on Days 1-5 and carboplatin IV AUC 4 on Day 8, or (2) treatment of choice (TC) of topotecan, pegylated liposomal doxorubicin (PLD), paclitaxel, or gemcitabine based on recommended dosing in 28-day cycles; participants initially randomized to TC were able to cross over to receive 30 mg/m2 G+C due to disease progression.	Drug: SGI-110 Drug: Treatment of Choice (topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) Drug: Carboplatin

Name	Type	Description	Arm Group Labels	Other Names
SGI-110	Drug		SGI-110 + Carboplatin SGI-110 + Carboplatin or TC	guadecitabine

Measure	Description	Time Frame
Stage 1: Dose Limiting Toxicities	Number of participants with dose limiting toxicities (DLTs) in Stage 1	Up to 12 months
Stage 2: Progression Free Survival	Progression free survival (PFS) time was defined as the time interval from the date of the first dose of study medication until the earlier of disease progression or death. Participants were treated with their assigned treatment [guadecitabine+carboplatin (G+C) or treatment choice (TC)] until disease progression or unacceptable treatment-related toxicity occurred.	Up to 24 months

Measure	Description	Time Frame
Objective Response Rate	The objective response rate (ORR) was defined as the proportion of participants who experienced an objective response (best overall response of complete response/full response or partial response, which was confirmed by a subsequent assessment at least 28 days later). Response categories were determined based on RECIST v1.1 criteria, or on modified Rustin (CA-125) criteria if response assessment could not be made using RECIST criteria.

Facility	Status	City	State	ZIP	Country	Contacts
Norris Comprehensive Cancer Center- University of Southern California		Los Angeles	California	90033	United States

PubMed Identifier	Type	Citation	Retractions
33289590	Derived	Cardenas H, Fang F, Jiang G, Perkins SM, Zhang C, Emerson RE, Hutchins G, Keer HN, Liu Y, Matei D, Nephew K. Methylomic Signatures of High Grade Serous Ovarian Cancer. Epigenetics. 2021 Nov;16(11):1201-1216. doi: 10.1080/15592294.2020.1853402. Epub 2020 Dec 8.
31831561	Derived	Oza AM, Matulonis UA, Alvarez Secord A, Nemunaitis J, Roman LD, Blagden SP, Banerjee S, McGuire WP, Ghamande S, Birrer MJ, Fleming GF, Markham MJ, Hirte HW, Provencher DM, Basu B, Kristeleit R, Armstrong DK, Schwartz B, Braly P, Hall GD, Nephew KP, Jueliger S, Oganesian A, Naim S, Hao Y, Keer H, Azab M, Matei D. A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer. Clin Cancer Res. 2020 Mar 1;26(5):1009-1016. doi: 10.1158/1078-0432.CCR-19-1638. Epub 2019 Dec 12.

ID	Title	Description
FG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
FG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2

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

Stage 1: Dose Limiting Toxicities

Number of participants with dose limiting toxicities (DLTs) in Stage 1

Safety data set includes data from all participants who received any amount of study drug, including any component of a multi-dose study treatment regimen.

Posted

Count of Participants

Participants

Up to 12 months

ID	Title	Description
OG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.

Units	Counts
Participants	OG00014 OG0016

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0014

Primary

Stage 2: Progression Free Survival

Progression free survival (PFS) time was defined as the time interval from the date of the first dose of study medication until the earlier of disease progression or death. Participants were treated with their assigned treatment [guadecitabine+carboplatin (G+C) or treatment choice (TC)] until disease progression or unacceptable treatment-related toxicity occurred.

Efficacy data set included all participants who received any amount of study drug.

Posted

Median

95% Confidence Interval

Days

Up to 24 months

ID	Title	Description
OG000	Stage 2: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG001	Stage 2: Treatment Choice	Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion).

Units	Counts

Secondary

Objective Response Rate

The objective response rate (ORR) was defined as the proportion of participants who experienced an objective response (best overall response of complete response/full response or partial response, which was confirmed by a subsequent assessment at least 28 days later). Response categories were determined based on RECIST v1.1 criteria, or on modified Rustin (CA-125) criteria if response assessment could not be made using RECIST criteria.

Efficacy data set included all participants who received any amount of study drug.

Posted

Number

95% Confidence Interval

Percent

Up to 24 months

ID	Title	Description
OG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.
OG002	Stage 2: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.

Secondary

Progression Free Survival at 6 Months

Progression free survival rate at 6 months is the proportion of participants who were alive and did not have disease progression at 6 months after start of treatment.

Efficacy data set included all participants who received any amount of study drug.

Posted

Number

95% Confidence Interval

Percent of participants

6 months

ID	Title	Description
OG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.
OG002	Stage 2: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG003	Stage 2: Treatment Choice

Secondary

Clinical Benefit Rate

Clinical benefit rate (CBR) was defined as the proportion of subjects who experienced a best overall response of complete response/full response or partial response (confirmed by a subsequent assessment at least 28 days later), or documented stable disease for at least 3 months after the first dose. Response categories were determined based on RECIST v1.1 criteria, then based on modified Rustin (CA-125) criteria if assessment could not be made using RECIST criteria.

Efficacy data set included all participants who received any amount of study drug.

Posted

Number

95% Confidence Interval

Percent of participants

Up to 24 months

ID	Title	Description
OG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.
OG002	Stage 2: Guadecitabine+Carboplatin 30 mg/m2

Secondary

CA-125 Levels

Percentage of participants with CA-125 reduction by ≥ 50% from baseline

Efficacy data set included all participants who received any amount of study drug.

Posted

Number

95% Confidence Interval

Percent of participants

Up to 24 months

ID	Title	Description
OG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.
OG002	Stage 2: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG003	Stage 2: Treatment Choice

Secondary

Duration of Response

Duration of response is defined as the time between the date of the first documentation of complete response/full response or partial response, and the date of disease progression or date of death due to any cause, or the last adequate tumor assessment prior to the start of subsequent anti-cancer therapy including crossing over to G+C from TC arm, whichever occurred earlier. Only participants who responded were included in the duration of response calculation.

Efficacy data set included all participants who received any amount of study drug.

Posted

Median

95% Confidence Interval

Days

Up to 24 months

ID	Title	Description
OG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.
OG002	Stage 2: Guadecitabine+Carboplatin 30 mg/m2

Secondary

Overall Survival

Overall survival was defined as the number of days from the day the participant was administered the first dose of study treatment to the date of death (regardless of cause). Survival time was censored on the last date the participant was known to be alive or lost to follow-up before reaching the event of death; in the TC group, time was censored at the date of crossover.

Efficacy data set included all participants who received any amount of study drug.

Posted

Median

95% Confidence Interval

Days

Up to 24 months

ID	Title	Description
OG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.
OG002	Stage 2: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.

Secondary

Stage 1: Pharmacokinetic Parameter Cmax

Time to maximum plasma concentration for guadecitabine, decitabine and carboplatin

The pharmacokinetic (PK) population included participants for which sufficient data were available to calculate PK parameters.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles)

ID	Title	Description
OG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.

Units	Counts
Participants

Secondary

Stage 1: Pharmacokinetic Parameter Tmax

Time to last measurable concentration for guadecitabine, decitabine and carboplatin

The pharmacokinetic (PK) population included participants for which sufficient data were available to calculate PK parameters.

Posted

Median

Full Range

Hours

Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles)

ID	Title	Description
OG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.

Units	Counts
Participants

Secondary

Stage 1: Pharmacokinetic Parameter AUC0-8

Area under the concentration-time curve from 0 to 8 hours (AUC0-8) for guadecitabine, decitabine and carboplatin

The pharmacokinetic (PK) population included participants for which sufficient data were available to calculate PK parameters.

Posted

Mean

Standard Deviation

Hours*ng/mL

Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles)

ID	Title	Description
OG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
OG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypotension	Vascular disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG0031 events1 affected49 at risk EG0040 events0 affected27 at risk
Anaphylactic reaction	Immune system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Pyrexia	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Adverse drug reaction	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Asthenia	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Fatigue	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Influenza like illness	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Pain	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Elective procedure	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Mental status change	Psychiatric disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
International normalized ratio increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Transaminases increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0012 events2 affected6 at risk EG0021 events1 affected51 at risk EG003
Anemia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0021 events1 affected51 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0023 events3 affected51 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Seizure	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Peripheral neuropathy sensory	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Radicular pain	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected6 at risk EG0028 events8 affected51 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0012 events2 affected6 at risk EG0021 events1 affected51 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0012 events2 affected6 at risk EG0020 events0 affected51 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0024 events4 affected51 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Diarrhea	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Gastrointestinal hemorrhage	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Large intestine perforation	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Intestinal perforation	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Abdominal abscess	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Portal vein thrombosis	Hepatobiliary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Pyoderma gangrenosum	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Gait disturbance	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Failure to thrive	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Hyponatremia	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Sepsis	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Pneumonia	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0021 events1 affected51 at risk EG003
Cellulitis	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Infection	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Lower respiratory tract infections	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Postoperative fever	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertension	Vascular disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0027 events7 affected51 at risk EG0036 events6 affected49 at risk EG0042 events2 affected27 at risk
Embolism	Vascular disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Flushing	Vascular disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected6 at risk EG0021 events1 affected51 at risk EG003
Hematoma	Vascular disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0023 events3 affected51 at risk EG003
Hypotension	Vascular disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Lymphedema	Vascular disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0021 events1 affected51 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0011 events1 affected6 at risk EG0023 events3 affected51 at risk EG003
Fatigue	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0009 events9 affected14 at risk EG0014 events4 affected6 at risk EG00233 events33 affected51 at risk EG003
Injection site reaction	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0008 events8 affected14 at risk EG0012 events2 affected6 at risk EG00223 events23 affected51 at risk EG003
Pyrexia	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0014 events4 affected6 at risk EG0028 events8 affected51 at risk EG003
Peripheral edema	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0012 events2 affected6 at risk EG0025 events5 affected51 at risk EG003
Adverse drug reaction	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0011 events1 affected6 at risk EG0022 events2 affected51 at risk EG003
Pain	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0025 events5 affected51 at risk EG003
Chills	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0024 events4 affected51 at risk EG003
Hernia pain	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Malaise	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0023 events3 affected51 at risk EG003
Peripheral swelling	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Early satiety	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0024 events4 affected51 at risk EG003
Asthenia	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0021 events1 affected51 at risk EG003
Injection site pain	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0004 events4 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Mass	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0012 events2 affected6 at risk EG0026 events6 affected51 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected6 at risk EG0024 events4 affected51 at risk EG003
Depression	Psychiatric disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0024 events4 affected51 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Perineal pain	Reproductive system and breast disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Vaginal discharge	Reproductive system and breast disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Vaginal ulceration	Reproductive system and breast disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Vulvovaginal swelling	Reproductive system and breast disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0025 events5 affected51 at risk EG003
Vaginal hemorrhage	Reproductive system and breast disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0012 events2 affected6 at risk EG0023 events3 affected51 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0023 events3 affected51 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0023 events3 affected51 at risk EG003
Stoma site pain	Injury, poisoning and procedural complications	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Weight decreased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Anion gap increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Aspartate aminotransferase	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected6 at risk EG0024 events4 affected51 at risk EG003
Bilirubin urine present	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Blood albumin decreased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Blood chloride decreased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Carbon dioxide decreased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Protein urine present	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Weight increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0011 events1 affected6 at risk EG0023 events3 affected51 at risk EG003
Specific gravity urine increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Urine ketone body present	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Urine leukocyte esterase positive	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Blood phosphorous decreased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Protein total decreased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Blood creatinine increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0027 events7 affected51 at risk EG003
International normalized ratio increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0021 events1 affected51 at risk EG003
Palpitations	Cardiac disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0024 events4 affected51 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0007 events7 affected14 at risk EG0015 events5 affected6 at risk EG00236 events36 affected51 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0005 events5 affected14 at risk EG0012 events2 affected6 at risk EG00216 events16 affected51 at risk EG003
Anemia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0007 events7 affected14 at risk EG0014 events4 affected6 at risk EG00216 events16 affected51 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0016 events6 affected6 at risk EG00212 events12 affected51 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0011 events1 affected6 at risk EG00214 events14 affected51 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0004 events4 affected14 at risk EG0012 events2 affected6 at risk EG0027 events7 affected51 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Dyspnea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected6 at risk EG0021 events1 affected51 at risk EG003
Hemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected6 at risk EG0023 events3 affected51 at risk EG003
Paranasal sinus hypersecretion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0023 events3 affected51 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0025 events5 affected51 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0022 events2 affected51 at risk EG003
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Upper respiratory tract infection	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Headache	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0010 events0 affected6 at risk EG0029 events9 affected51 at risk EG003
Dizziness	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0025 events5 affected51 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0024 events4 affected51 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0023 events3 affected51 at risk EG003
Parasthesia	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Tremor	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Ear discomfort	Ear and labyrinth disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG00010 events10 affected14 at risk EG0012 events2 affected6 at risk EG00238 events38 affected51 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0006 events6 affected14 at risk EG0012 events2 affected6 at risk EG00232 events32 affected51 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0005 events5 affected14 at risk EG0014 events4 affected6 at risk EG00222 events22 affected51 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0004 events4 affected14 at risk EG0012 events2 affected6 at risk EG00221 events21 affected51 at risk EG003
Diarrhea	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0004 events4 affected14 at risk EG0011 events1 affected6 at risk EG00221 events21 affected51 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0011 events1 affected6 at risk EG00211 events11 affected51 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG00210 events10 affected51 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0012 events2 affected6 at risk EG0026 events6 affected51 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0012 events2 affected6 at risk EG0024 events4 affected51 at risk EG003
Gastroesophageal reflux disease	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0012 events2 affected6 at risk EG0028 events8 affected51 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0010 events0 affected6 at risk EG0024 events4 affected51 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0023 events3 affected51 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0023 events3 affected51 at risk EG003
Anorectal discomfort	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0012 events2 affected6 at risk EG0021 events1 affected51 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0024 events4 affected51 at risk EG003
Hemorrhoids	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Epigastric discomfort	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Gastrointestinal hemorrhage	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Lip dry	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Rectal hemorrhage	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected6 at risk EG0025 events5 affected51 at risk EG003
Hematuria	Renal and urinary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Micturition urgency	Renal and urinary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0011 events1 affected6 at risk EG0027 events7 affected51 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0026 events6 affected51 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Onycholysis	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0013 events3 affected6 at risk EG0027 events7 affected51 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Swelling face	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0011 events1 affected6 at risk EG0029 events9 affected51 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected6 at risk EG00211 events11 affected51 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG00210 events10 affected51 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0022 events2 affected51 at risk EG003
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0025 events5 affected51 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0011 events1 affected6 at risk EG0023 events3 affected51 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0026 events6 affected51 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0025 events5 affected51 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected6 at risk EG0023 events3 affected51 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Hypomagnesemia	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0014 events4 affected6 at risk EG00215 events15 affected51 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0006 events6 affected14 at risk EG0012 events2 affected6 at risk EG00214 events14 affected51 at risk EG003
Hypokalemia	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0012 events2 affected6 at risk EG0026 events6 affected51 at risk EG003
Hyponatremia	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 events3 affected14 at risk EG0011 events1 affected6 at risk EG0023 events3 affected51 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected6 at risk EG0024 events4 affected51 at risk EG003
Hyperglycemia	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected6 at risk EG0021 events1 affected51 at risk EG003
Hypoalbuminemia	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0021 events1 affected51 at risk EG003
Hypocalcemia	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected6 at risk EG0022 events2 affected51 at risk EG003
Hypoglycemia	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Hypophosphatemia	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Bacteriuria	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Breast cellulitis	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Localized infection	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0021 events1 affected51 at risk EG003
Rhinitis	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected6 at risk EG0023 events3 affected51 at risk EG003
Rocky mountain spotted fever	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0002 events2 affected14 at risk EG0011 events1 affected6 at risk EG0028 events8 affected51 at risk EG003
Vaginitis bacterial	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected6 at risk EG0020 events0 affected51 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Enterococcal infection	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Impetigo	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0020 events0 affected51 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected6 at risk EG0021 events1 affected51 at risk EG003

ID	Term
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D010049	Ovarian Diseases
D000291	Adnexal Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D005833	Genital Neoplasms, Female
D014565	Urogenital Neoplasms
D000091662	Genital Diseases
D004700	Endocrine System Diseases
D006058	Gonadal Disorders

ID	Term
C580831	guadecitabine
D019772	Topotecan
C506643	liposomal doxorubicin
D017239	Paclitaxel
D000093542	Gemcitabine
D016190	Carboplatin

ID	Term
D002166	Camptothecin
D000470	Alkaloids
D006571	Heterocyclic Compounds
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D056831	Coordination Complexes

ID	Title	Description
BG000	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
BG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.
BG002	Stage 2: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.
BG003	Stage 2: Treatment Choice	Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion. Participants initially randomized to TC were able to cross over to receive 30 mg/m2 G+C due to disease progression.
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	Stage 1: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.	14	14	8	14	14	14
EG001	Stage 1: Guadecitabine+Carboplatin 45 mg/m2	Guadecitabine 45 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles. Due to dose limiting toxicities, the guadecitabine dose for this group was reduced from 45 mg/m2 to 30 mg/m2 after Cycle 1 for 4 of 6 participants and the carboplatin dose was reduced for 2 of 6 participants.	4	6	4	6	6	6
EG002	Stage 2: Guadecitabine+Carboplatin 30 mg/m2	Guadecitabine 30 mg/m2 on Days 1-5 and carboplatin AUC 4 on Day 8 of 28-day treatment cycles.	43	51	26	51	50	51
EG003	Stage 2: Treatment Choice	Treatment was selected at the investigator's discretion and administered based on recommended dosing for topotecan (3.5-4.0 mg/m2/wk administered on Days 1, 8, and 15 via IV infusion); PLD (40-50 mg/m2 administered on Day 1 via IV infusion), paclitaxel (60-80 mg/m2/wk administered on Days 1, 8, 15, and 22 via IV infusion), or gemcitabine (800-1000 mg/m2 administered on Days 1, 8, and 15 via IV infusion).	18	49	24	49	49	49
EG004	Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2	Crossover from treatment choice to the guadecitabine+carboplatin combination treatment arm was permitted for participants after evidence of disease progression.	22	27	12	27	27	27