A Study LY2228820 for Recurrent Ovarian Cancer | NCT01663857

ID	Type	Description	Link
I1D-MC-JIAE	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
Phase 1b (Cohort 1) LY2228820 200 milligrams (mg)	Experimental	Cohort 1: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 milligrams per square meter (mg/m^2) administered intravenously (IV) over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.. Cohort 1: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.	Drug: LY2228820 Drug: Carboplatin Drug: Gemcitabine
Phase 1b (Cohort 2) LY2228820 300 mg	Experimental	Cohort 2: Cycles 1-6 (21 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3. Cohort 2: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.	Drug: LY2228820 Drug: Carboplatin Drug: Gemcitabine
Phase 2 (Arm A) LY2228820 200 mg	Experimental	Arm A: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3. Arm A: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.	Drug: LY2228820 Drug: Carboplatin Drug: Gemcitabine
Phase 2 (Arm B) Placebo

Name	Type	Description	Arm Group Labels	Other Names
LY2228820	Drug	Administered Orally	Phase 1b (Cohort 1) LY2228820 200 milligrams (mg) Phase 1b (Cohort 2) LY2228820 300 mg Phase 2 (Arm A) LY2228820 200 mg

Measure	Description	Time Frame
Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])	Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).	Cycle 1 (21 Days)
Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin	PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	Randomization to Date of Disease Progression or Death from any cause (up to 3 years)

Measure	Description	Time Frame
Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)	Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9am-5pm Eastern time *UTC/GMT-5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
St Josephs Hospital and Medical Center		Phoenix	Arizona	85013	United States
Arizona Oncology Associates, P.C.

PubMed Identifier	Type	Citation	Retractions
31791552	Derived	Vergote I, Heitz F, Buderath P, Powell M, Sehouli J, Lee CM, Hamilton A, Fiorica J, Moore KN, Teneriello M, Golden L, Zhang W, Pitou C, Bell R, Campbell R, Farrington DL, Bell-McGuinn K, Wenham RM. A randomized, double-blind, placebo-controlled phase 1b/2 study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine and carboplatin versus gemcitabine and carboplatin for women with recurrent platinum-sensitive ovarian cancer. Gynecol Oncol. 2020 Jan;156(1):23-31. doi: 10.1016/j.ygyno.2019.11.006. Epub 2019 Nov 29.

ID	Title	Description
FG000	Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin	Cohort 1:LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10 of a 21-day cycle. Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle. Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 16, 2017	Mar 5, 2019

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Calculate Percentage

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Primary

Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])

Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).

All participants who received at least one dose of study drug in Phase 1b.

Posted

Number

milligrams (mg)

Cycle 1 (21 Days)

ID	Title	Description
OG000	LY2228820 + Gemcitabine + Carboplatin	Cohort 1 : LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6) Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10 Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3 Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10 Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 Cohort 1 and 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)

Units	Counts
Participants	OG0008

Title

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Title	Measurements
	OG000200

Primary

Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin

PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

All participants in Phase 2 who received at least one dose of study drug.

Posted

Median

90% Confidence Interval

months

Randomization to Date of Disease Progression or Death from any cause (up to 3 years)

ID	Title	Description
OG000	LY2228820 + Gemcitabine +Carboplatin	Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of 21-day cycles. Gemcitabine 1000 mg/m2 IV over 30 min on Days 3 and 10 of 21-day cycles. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of 21-day cycles. Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)
OG001	Placebo + Gemcitabine + Carboplatin	Arm B: Placebo orally every 12 hrs. on Days 1-10 of 21-day cycles. Gemcitabine 1000 mg/m2 IV over 30 min on Days 3 and 10 of 21-day cycles. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. n Day 3 of 21-day cycles. Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)

Secondary

Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)

Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.

All participants who received at least one dose of study drug in Phase 2.

Posted

Number

percentage of participants

Baseline to Disease Progression (up to 3 years)

ID	Title	Description
OG000	LY2228820 + Gemcitabine +Carboplatin	Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min.(+ 15 min.) on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day. Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+).
OG001	Placebo + Gemcitabine + Carboplatin	Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle. Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)

Secondary

Phase 2: Overall Survival

Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.

All participants in Phase 2 who received at least one dose of drug.

Posted

Median

90% Confidence Interval

months

Baseline to Date of Death from any cause (up to 5 years)

ID	Title	Description
OG000	LY2228820 + Gemcitabine +Carboplatin	Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day. Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+).
OG001	Placebo + Gemcitabine + Carboplatin	Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle. Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)

Units	Counts
Participants

Secondary

Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820

PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.

All participants in Phase 1b and Phase 2 who received at least one dose of study drug and had evaluable PK data.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanograms * hr per milliliter (ng*hr/mL)

Phase1b:Cycle(C)1 Day(D)1:Predose(PRD),0.5,1,2,4,6,8 hours(hr)postdose(PD); C1D10:PRD,0.5,1,2,8hrPD; C2D10:PRD,0.5,1,2,4,6,8,12hrPD; C7D3:PRD,0.5,1,2,4,6hrPD; Phase 2: C1D3:PRD,0.5,1,2,4,6,8hrPD; C1D10:PRD,0.5,1,2,4,6,8hrPD; C7D3:PRD,0.5,1,2,4,6,8hrPD

ID	Title	Description
OG000	200 mg LY2228820	Phase 1b (Cohort 1) and Phase 2 (Arm A): LY2228820 200 mg administered orally every 12 hours on Days 1-10, Cycles 1-6 of a 21 day cycle. .
OG001	300 mg LY2228820	Phase 1b (Cohort 2) and Phase 2 (Arm A) in the maintenance portion with LY2228820 300 mg administered orally every 12 hours on Days 1-14 Cycle 7+ of a 28-day cycle.

Units	Counts
Participants

Secondary

Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score

The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = "not at all" and 4 = "very much." Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life.

All participants in Phase 2 who received at least one dose of study drug and had at least one post baseline assessment.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Study Completion (up to 3 years)

ID	Title	Description
OG000	LY2228820 + Gemcitabine +Carboplatin	Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day. Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)
OG001	Placebo + Gemcitabine + Carboplatin

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0025 events3 affected58 at risk EG0030 events0 affected52 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0022 events1 affected58 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0027 events5 affected58 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0024 events3 affected58 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0023 events3 affected58 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0023 events2 affected58 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events1 affected58 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0025 events2 affected58 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0003 events1 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Subileus	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0026 events2 affected58 at risk EG003
General physical health deterioration	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Malaise	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Pyrexia	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Anaphylactic reaction	Immune system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Abscess	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Appendicitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Erysipelas	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0023 events1 affected58 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Lung infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events1 affected58 at risk EG003
Pelvic infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Pneumonia	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Sepsis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Ureteritis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Urostomy complication	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Nuclear magnetic resonance imaging abdominal abnormal	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Platelet count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Dizziness	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Headache	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Presyncope	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Syncope	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Drug reaction with eosinophilia and systemic symptoms	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected2 at risk EG0020 events0 affected58 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0008 events5 affected6 at risk EG0014 events1 affected2 at risk EG00291 events32 affected58 at risk EG00373 events25 affected52 at risk
Increased tendency to bruise	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0023 events3 affected58 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0028 events5 affected58 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0023 events2 affected58 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG00024 events5 affected6 at risk EG0014 events2 affected2 at risk EG00272 events26 affected58 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0009 events4 affected6 at risk EG0010 events0 affected2 at risk EG00240 events17 affected58 at risk EG003
Palpitations	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0026 events6 affected58 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0024 events4 affected58 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Glaucoma	Eye disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Vision blurred	Eye disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0023 events3 affected58 at risk EG003
Visual impairment	Eye disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected2 at risk EG0026 events6 affected58 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG00213 events12 affected58 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0025 events5 affected58 at risk EG003
Anal incontinence	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0005 events2 affected6 at risk EG0011 events1 affected2 at risk EG00231 events23 affected58 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0005 events4 affected6 at risk EG0011 events1 affected2 at risk EG00240 events23 affected58 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0023 events3 affected58 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected2 at risk EG0023 events3 affected58 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0008 events4 affected6 at risk EG0010 events0 affected2 at risk EG00239 events31 affected58 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0010 events0 affected2 at risk EG00210 events9 affected58 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0003 events3 affected6 at risk EG0010 events0 affected2 at risk EG00223 events17 affected58 at risk EG003
Chills	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Fatigue	General disorders	MedDRA 20.1	Systematic Assessment	EG00011 events5 affected6 at risk EG0010 events0 affected2 at risk EG00250 events40 affected58 at risk EG003
Oedema peripheral	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0029 events7 affected58 at risk EG003
Peripheral swelling	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Pyrexia	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0029 events8 affected58 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0027 events5 affected58 at risk EG003
Bronchitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events1 affected58 at risk EG003
Cystitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0023 events3 affected58 at risk EG003
Fungal skin infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Pneumonia	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Sinusitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0004 events3 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0026 events5 affected58 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG00214 events8 affected58 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0003 events2 affected6 at risk EG0010 events0 affected2 at risk EG0028 events7 affected58 at risk EG003
Wrist fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0005 events2 affected6 at risk EG0012 events1 affected2 at risk EG00242 events25 affected58 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0005 events3 affected6 at risk EG0010 events0 affected2 at risk EG00228 events17 affected58 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0010 events0 affected2 at risk EG00212 events9 affected58 at risk EG003
Blood creatinine increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Blood urea increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected2 at risk EG0020 events0 affected58 at risk EG003
Ejection fraction decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0023 events2 affected58 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected2 at risk EG00276 events26 affected58 at risk EG003
Platelet count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0006 events1 affected6 at risk EG0012 events1 affected2 at risk EG00253 events21 affected58 at risk EG003
Weight decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events1 affected58 at risk EG003
White blood cell count decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG00012 events3 affected6 at risk EG0010 events0 affected2 at risk EG00247 events20 affected58 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0003 events3 affected6 at risk EG0010 events0 affected2 at risk EG00215 events14 affected58 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0024 events1 affected58 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected2 at risk EG0022 events2 affected58 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0024 events2 affected58 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0010 events0 affected2 at risk EG0025 events3 affected58 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected2 at risk EG00211 events7 affected58 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0026 events6 affected58 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG00210 events7 affected58 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0025 events5 affected58 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0024 events3 affected58 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0025 events5 affected58 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0024 events4 affected58 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Osteopenia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0027 events4 affected58 at risk EG003
Dizziness	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0010 events0 affected2 at risk EG00213 events12 affected58 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0025 events5 affected58 at risk EG003
Headache	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0004 events3 affected6 at risk EG0010 events0 affected2 at risk EG00210 events10 affected58 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0003 events1 affected6 at risk EG0010 events0 affected2 at risk EG0026 events5 affected58 at risk EG003
Syncope	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Tremor	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0027 events6 affected58 at risk EG003
Adjustment disorder with depressed mood	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0010 events0 affected2 at risk EG0025 events4 affected58 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0011 events1 affected2 at risk EG0023 events3 affected58 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Vaginal discharge	Reproductive system and breast disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Vulvovaginal pruritus	Reproductive system and breast disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected2 at risk EG00211 events11 affected58 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG00220 events17 affected58 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0023 events3 affected58 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected2 at risk EG0026 events5 affected58 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected2 at risk EG0027 events7 affected58 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0010 events0 affected2 at risk EG0027 events7 affected58 at risk EG003
Paranasal sinus discomfort	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0021 events1 affected58 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0022 events2 affected58 at risk EG003
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected2 at risk EG00210 events10 affected58 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0023 events3 affected58 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG00210 events7 affected58 at risk EG003
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0023 events3 affected58 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0025 events4 affected58 at risk EG003
Social problem	Social circumstances	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected2 at risk EG0020 events0 affected58 at risk EG003
Flushing	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected2 at risk EG0020 events0 affected58 at risk EG003
Hypertension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected2 at risk EG0023 events2 affected58 at risk EG003

ID	Title	Description
BG000	Phase 1b: Cohort 1: LY2228820 +Gemcitabine+Carboplatin	Cohort 1:LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10. Carboplatin area under the concentration curve administered intravenously (IV) over 30 minutes (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3. Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6).
BG001	Phase 1b: Cohort 2: LY2228820 +Gemcitabine+Carboplatin	Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg/m2 administered IV over 30 min on Days 3 and 10. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3. Cohort 2:LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+).
BG002	Arm A: LY2228820 + Gemcitabine + Carboplatin	Arm A:LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3. Arm A:LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).
BG003	Arm B Placebo + Gemcitabine +Carboplatin	Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3. Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).
BG004	Total	Total of all reporting groups

ID	Term
D000077216	Carcinoma, Ovarian Epithelial
D005185	Fallopian Tube Neoplasms

ID	Term
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D010051	Ovarian Neoplasms
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
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
D005184	Fallopian Tube Diseases

ID	Term
D056831	Coordination Complexes
D009930	Organic Chemicals
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin	Cohort 1: LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6) Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10 Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3 Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)	3	6	3	6	6	6
EG001	Phase 1b: Cohort 2: LY2228820 + Gemcitabine + Carboplatin	Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10 Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 Cohort 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)	1	2	1	2	2	2
EG002	Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin	Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)	30	58	26	58	58	58
EG003	Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin	Arm B: Placebo orally every 12 hrs. on Days 1-10 Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)	31	52	12	52	52	52