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Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Study of LY2228820, a p38MAPK Inhibitor, plus Gemcitabine and Carboplatin versus Gemcitabine and Carboplatin for Women with Platinum-Sensitive Ovarian Cancer

Summary
EudraCT number	2011-005197-40
Trial protocol	DE BE
Global end of trial date	11 May 2018

Results information
Results version number	v1(current)
This version publication date	24 May 2019
First version publication date	24 May 2019
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

I1D-MC-JIAE

ISRCTN number

US NCT number

NCT01663857

WHO universal trial number (UTN)

Other trial identifiers

Trial Alias: 12517

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46825

Public contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,

Scientific contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

11 May 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

11 May 2018

Was the trial ended prematurely?

Main objective of the trial

Phase 1b - to determine the recommended Phase 2 dose of LY2228820 that can be safely administered with gemcitabine and carboplatin Phase 2 - to compare the progression-free survival in patients treated with LY2228820 plus gemcitabine and carboplatin versus placebo plus gemcitabine and carboplatin

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Jul 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 20

Country: Number of subjects enrolled

Germany: 26

Country: Number of subjects enrolled

Australia: 10

Country: Number of subjects enrolled

United States: 62

Worldwide total number of subjects

118

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Participants in Phase 1b are considered to have completed the study if they experience a dose-limiting toxicity or completed the Pharmacokinetic (PK) sampling set. Participants in Phase 2 are considered to have completed if they die due to any cause or who are alive and on study at conclusion, but are off treatment.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer

Are arms mutually exclusive

Yes

Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin

Arm description

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

Arm type

Experimental

Investigational medicinal product name

LY2228820

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

LY2228820 200 milligrams (mg) administered orally every 12 hours on days 1-10 of Cycles 1-6. LY2228820 300 mg administered orally every 12 hours on days 1-14 of Cycles 7+

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

LY188011

Other name

Gemzar

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Gemcitabine 1000 mg/m^2 administered intravenously (IV) over 30 minutes on Days 3 and 10 of a 21-day cycle (Cycles 1-6)

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Carboplatin AUC 4 (max dose 600 mg) IV over 30 minutes on Day 3 of a 21-day cycle (Cycles 1-6)

Phase 1b : Cohort 2: LY2228820 + Gemcitabine + Carboplatin

Arm description

Cohort 2: LY2228820 300 mg administered orally every 12 hours on Days 1-10 of 21-day Cycle (Cycles 1-6). Gemcitabine 1000 mg/m^2 administered intravenously (IV) over 30 minutes on Days 3 and 10 of a 21-day cycle (Cycles 1-6). Carboplatin AUC 4 (maximum dose 600mg) IV over 30 minutes on Day 3 of a 21-day cycle (Cycles 1-6). Cohort 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+).

Arm type

Experimental

Investigational medicinal product name

LY2228820

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

LY2228820 200 mg administered orally every 12 hours on days 1-10 of 21-day cycle (Cycles 1-6). LY2228820 300 mg administered orally every 12 hours on days 1-14 of a 28-day cycle (Cycles 7+).

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

LY188011

Other name

Gemzar

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Gemcitabine 1000 mg/m^2 administered intravenously (IV) over 30 minutes (min) on Days 3 and 10 of a 21-day cycle (Cycles 1-6)

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Carboplatin AUC 4 (max dose 600 mg) IV over 30 minutes on Day 3 of a 21-day cycle (Cycles 1-6)

Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin

Arm description

Arm A: LY2228820 200 mg orally every 12 hours on Days 1-10 of 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg/m^2 administered intravenously (IV) over 30 minutes on Days 3 and 10 of a 21-day cycle (Cycles 1-6). Carboplatin AUC 4 (maximum dose 600mg) IV over 30 minutes on Day 3 of a 21-day cycle (Cycles 1-6). Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day-cycle (Cycles 7+).

Arm type

Experimental

Investigational medicinal product name

LY2228820

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

LY2228820 200 mg administered orally every 12 hours on days 1-10 of 21-day cycle (Cycles 1-6). LY2228820 300 mg administered orally every 12 hours on days 1-14 of a 28-day cycle (Cycles 7+).

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

LY188011

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Gemcitabine 1000 mg/m^2 administered intravenously (IV) over 30 minutes on Days 3 and 10 of a 21-day cycle (Cycles 1-6)

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Carboplatin AUC 4 (max dose 600 mg) IV over 30 minutes on Day 3 of a 21-day cycle (Cycles 1-6)

Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin

Arm description

Arm B: Placebo orally every 12 hours on Days 1-10 of 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg/m^2 administered intravenously (IV) over 30 minutes on Days 3 and 10 of a 21-day cycle (Cycles 1-6). Carboplatin AUC 4 (maximum dose 600mg) IV over 30 minutes on Day 3 of a 21-day cycle (Cycles 1-6). Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)

Arm type

Placebo Comparator

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo administered orally every 12 hours on days 1-10 of 21-day cycle (Cycles 1-6). Placebo administered orally every 12 hours on days 1-14 of a 28-day cycle (Cycles 7+).

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

LY188011

Other name

Gemzar

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Gemcitabine 1000 mg/m^2 administered intravenously (IV) over 30 minutes on Days 3 and 10 of a 21-day cycle (Cycles 1-6)

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Carboplatin AUC 4 (max dose 600 mg) IV over 30 minutes on Day 3 of a 21-day cycle (Cycles 1-6)

Number of subjects in period 1	Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin	Phase 1b : Cohort 2: LY2228820 + Gemcitabine + Carboplatin	Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin	Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin
Started	6	2	58	52
Recieved at Least One Dose of Study Drug	6	2	58	52
Completed	6	1	48	48
Not completed	0	1	10	4
Consent withdrawn by subject	-	1	7	3
Lost to follow-up	-	-	3	1

Baseline characteristics

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Reporting group title

Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin

Reporting group description

Reporting group title

Phase 1b : Cohort 2: LY2228820 + Gemcitabine + Carboplatin

Reporting group description

Reporting group title

Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin

Reporting group description

Reporting group title

Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin

Reporting group description

Reporting group values	Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin	Phase 1b : Cohort 2: LY2228820 + Gemcitabine + Carboplatin	Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin	Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin	Total
Number of subjects	6	2	58	52	118
Age categorical
Units: Subjects
18-64 years	4	1	32	30	67
65-84 years	2	1	26	22	51
Gender categorical
Units: Subjects
Female	6	2	58	52	118
Male	0	0	0	0	0
Race
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0
Asian	0	0	0	2	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	1	1	0	2
White	6	1	57	49	113
More than one race	0	0	0	0	0
Unknown or Not Reported	0	0	0	1	1
Region of Enrollment
Units: Subjects
Belgium	0	0	11	9	20
United States	5	2	30	25	62
Australia	0	0	4	6	10
Germany	1	0	13	12	26
Maintenance Therapy as a Part of or After a First Line Platinum Regimen
Measure Analysis Population Description: Maintenance therapy as part of or after first line platinum regimen data was used as a cofactor in the analysis of Progression Free Survival (PFS). Zero participants analyzed for Phase 1 portion of the study. Data was collected only from participants treated in the Phase 2 portion of the study.
Units: Subjects
Received Maintenance Therapy	0	0	7	7	14
Did Not Receive Maintenance Therapy	0	0	15	15	30
Data Missing or Not Collected	6	2	36	30	74

End points

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Reporting group title

Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin

Reporting group description

Reporting group title

Phase 1b : Cohort 2: LY2228820 + Gemcitabine + Carboplatin

Reporting group description

Reporting group title

Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin

Reporting group description

Reporting group title

Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin

Reporting group description

Subject analysis set title

Phase 1b

Subject analysis set type

Sub-group analysis

Subject analysis set description

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. Phase 1b: Cohort 2: LY2228820 + Gemcitabine + Carboplatin: Cohort 2: LY2228820 300 milligrams (mg) administered orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg/m2 administered intravenously (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

Subject analysis set title

LY2228820 200 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

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.

Subject analysis set title

LY2228820 300 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

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+ on a 28 day cycle.

Subject analysis set title

Arm A: LY2228820 + Gemcitabine + Carboplatin

Subject analysis set type

Sub-group analysis

Subject analysis set description

Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 (Cycles 1-6). Gemcitabine 1000 mg/m2 IV over 30 minutes on Days 3 and 10. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 minutes on Day 3. Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).

Subject analysis set title

Arm B Placebo + Gemcitabine +Carboplatin

Subject analysis set type

Sub-group analysis

Subject analysis set description

Arm B: Placebo orally every 12 hrs. on Days 1-10 (Cycles 1-6). Gemcitabine 1000 mg/m2 IV over 30 minutes on Days 3 and 10. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 minutes on Day 3. Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+).

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

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End point title

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

End point description

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).

End point type

Primary

End point timeframe

Cycle 1 (21 Days)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not performed for Recommended Phase 2 Dose for this primary endpoint as there were no comparison groups.

End point values	Phase 1b
Number of subjects analysed	8 ^[2]
Units: milligrams (mg)
number (not applicable)	200

Notes
[2] - All participants who received at least one dose of study drug in Phase 1b.

No statistical analyses for this end point

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

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End point title

Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin ^[3]

End point description

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.

End point type

Primary

End point timeframe

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

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Phase 1b was conducted to determine recommended Phase 2 dose, PFS was assessed on participants in Phase 2 only.

End point values	Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin	Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin
Number of subjects analysed	58 ^[4]	52 ^[5]
Units: Months
median (confidence interval 90%)	10.25 (7.85 to 10.87)	8.44 (7.56 to 9.33)

Notes
[4] - All participants in Phase 2 who received at least one dose of study drug.
[5] - All participants in Phase 2 who received at least one dose of study drug.

Phase 2 Progression-free Survival

Comparison groups

Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin v Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4

Method

Logrank

Confidence interval

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

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End point title

Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate) ^[6]

End point description

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.

End point type

Secondary

End point timeframe

Baseline to Disease Progression ( up to 3 years)

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Phase 1b was conducted to determine recommended Phase 2 dose, Overall Response Rate was assessed on participants in Phase 2 only.

End point values	Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin	Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin
Number of subjects analysed	58 ^[7]	52 ^[8]
Units: Percentage of Participants
number (not applicable)	46.6	46.2

Notes
[7] - All participants who received at least one dose of study drug in Phase 2.
[8] - All participants who received at least one dose of study drug in Phase 2.

No statistical analyses for this end point

Secondary: Phase 2: Overall Survival

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End point title

Phase 2: Overall Survival ^[9]

End point description

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

End point type

Secondary

End point timeframe

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

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Phase 1b was conducted to determine recommended Phase 2 dose, overall survival data was collected for participants in Phase 2 only.

End point values	Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin	Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin
Number of subjects analysed	58 ^[10]	52 ^[11]
Units: Months
median (confidence interval 90%)	29.17 (23.26 to 52.40)	25.10 (21.95 to 33.68)

Notes
[10] - All participants who received at least one dose of study drug in Phase 2.
[11] - All participants who received at least one dose of study drug in Phase 2.

Phase 2: Overall Survival

Comparison groups

Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin v Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin

Number of subjects included in analysis

110

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4686

Method

Logrank

Confidence interval

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

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End point title

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

End point description

PK parameters after administration of LY2228820 for both Phase 1b and Phase 2. Analysis Population Description: All participants in Phase 1b and Phase 2 who received at least one dose of study drug and had evaluable PK data.

End point type

Secondary

End point timeframe

Phase 1b: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

End point values	LY2228820 200 mg	LY2228820 300 mg
Number of subjects analysed	13 ^[12]	10 ^[13]
Units: nanogramshr per milliliter (nghr/mL)
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1 (n=6, n=2)	3470 ( 91 )	3560 ( 1 )
Cycle 1 Day 3 (n=7, n=0)	3170 ( 22 )	0 ( 0 )
Cycle 1 Day 10 (n=11, n=1)	4270 ( 62 )	9350 ( 0 )
Cycle 2 Day 10 (n=5, n=1)	3270 ( 38 )	3490 ( 0 )
Cycle 7 Day 3 (n=0, n=10)	0 ( 0 )	7230 ( 72 )

Notes
[12] - Zero participants analyzed for LY2228820 200 mg Cycle 7 Day 3, no evaluable PK data.
[13] - Zero participants analyzed for LY2228820 300 mg Cycle 1 Day 3, no evaluable PK data.

No statistical analyses for this end point

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

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End point title

Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Score ^[14]

End point description

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

End point type

Secondary

End point timeframe

Baseline, Study Completion (up to 3 years)

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Phase 1b was conducted to determine recommended Phase 2 dose, Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Score was assessed on Phase 2 participants only.

End point values	Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin	Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin
Number of subjects analysed	58	52
Units: Units on a Scale
arithmetic mean (standard deviation)	-0.6 ( 21.14 )	-8.9 ( 19.92 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to 4.5 years

Adverse event reporting additional description

I1D-MC-JIAE

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Phase 1b: LY2228820-200mg+Gemcitabine+Carboplatin

Reporting group description

Reporting group title

Phase 1b: LY2228820-300mg+Gemcitabine+Carboplatin

Reporting group description

Reporting group title

Phase 2: LY2228820-200mg+Gemcitabine+Carboplatin

Reporting group description

Reporting group title

Phase 2: Placebo+Gemcitabine+Carboplatin

Reporting group description

Serious adverse events	Phase 1b: LY2228820-200mg+Gemcitabine+Carboplatin	Phase 1b: LY2228820-300mg+Gemcitabine+Carboplatin	Phase 2: LY2228820-200mg+Gemcitabine+Carboplatin	Phase 2: Placebo+Gemcitabine+Carboplatin
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 6 (50.00%)	1 / 2 (50.00%)	26 / 58 (44.83%)	12 / 52 (23.08%)
number of deaths (all causes)	3	1	30	31
number of deaths resulting from adverse events	0	0	0	1
General disorders and administration site conditions
general physical health deterioration
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 58 (3.45%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
malaise
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
pyrexia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
anaphylactic reaction
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
dyspnoea
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 58 (3.45%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
pleural effusion
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
pneumonitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
alanine aminotransferase increased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
aspartate aminotransferase increased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
nuclear magnetic resonance imaging abdominal abnormal
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
platelet count decreased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
cervical vertebral fracture
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
fall
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
infusion related reaction
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
thermal burn
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
urostomy complication
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
dizziness
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
headache
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
presyncope
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
syncope
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	3 / 58 (5.17%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	5 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
febrile neutropenia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
leukopenia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
neutropenia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
thrombocytopenia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	5 / 58 (8.62%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	7 / 7	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
abdominal distension
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
abdominal pain
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	3 / 58 (5.17%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
abdominal pain upper
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ascites
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	3 / 58 (5.17%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
constipation
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
diarrhoea
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ileus
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 58 (3.45%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
nausea
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	2 / 52 (3.85%)
occurrences causally related to treatment / all	1 / 1	0 / 0	5 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
small intestinal obstruction
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
subileus
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
vomiting
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	2 / 52 (3.85%)
occurrences causally related to treatment / all	1 / 1	0 / 0	6 / 6	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
cholecystitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
drug reaction with eosinophilia and systemic symptoms
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
rash maculo-papular
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
acute kidney injury
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
flank pain
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
joint effusion
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
abscess
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
appendicitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
bacteraemia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
clostridium difficile infection
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
erysipelas
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
gastroenteritis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
lung infection
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
pelvic infection
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
pneumonia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 58 (3.45%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
pyelonephritis acute
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
sepsis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ureteritis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
urinary tract infection
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
hypokalaemia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	1 / 52 (1.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
hypophosphataemia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Phase 1b: LY2228820-200mg+Gemcitabine+Carboplatin	Phase 1b: LY2228820-300mg+Gemcitabine+Carboplatin	Phase 2: LY2228820-200mg+Gemcitabine+Carboplatin	Phase 2: Placebo+Gemcitabine+Carboplatin
Total subjects affected by non serious adverse events
subjects affected / exposed	6 / 6 (100.00%)	2 / 2 (100.00%)	58 / 58 (100.00%)	52 / 52 (100.00%)
Vascular disorders
flushing
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	4 / 52 (7.69%)
occurrences all number	0	0	0	5
hypertension
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	1 / 52 (1.92%)
occurrences all number	1	0	3	1
General disorders and administration site conditions
chills
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 58 (1.72%)	4 / 52 (7.69%)
occurrences all number	1	0	1	5
fatigue
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	5 / 6 (83.33%)	0 / 2 (0.00%)	40 / 58 (68.97%)	38 / 52 (73.08%)
occurrences all number	11	0	50	48
oedema peripheral
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	7 / 58 (12.07%)	7 / 52 (13.46%)
occurrences all number	0	0	9	8
peripheral swelling
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	3 / 52 (5.77%)
occurrences all number	0	0	1	3
pyrexia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	8 / 58 (13.79%)	6 / 52 (11.54%)
occurrences all number	1	0	9	7
Immune system disorders
drug hypersensitivity
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	5 / 58 (8.62%)	5 / 52 (9.62%)
occurrences all number	0	0	7	5
Social circumstances
social problem
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	0	1	0	0
Reproductive system and breast disorders
vaginal discharge
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	3 / 52 (5.77%)
occurrences all number	0	0	0	3
vulvovaginal pruritus
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	0 / 52 (0.00%)
occurrences all number	1	0	2	0
Respiratory, thoracic and mediastinal disorders
cough
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	11 / 58 (18.97%)	12 / 52 (23.08%)
occurrences all number	0	1	11	12
dyspnoea
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	17 / 58 (29.31%)	9 / 52 (17.31%)
occurrences all number	0	0	20	10
dyspnoea exertional
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	3 / 58 (5.17%)	3 / 52 (5.77%)
occurrences all number	0	0	3	3
epistaxis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	5 / 58 (8.62%)	1 / 52 (1.92%)
occurrences all number	0	2	6	1
hypoxia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	0	0
nasal congestion
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	7 / 58 (12.07%)	4 / 52 (7.69%)
occurrences all number	0	1	7	5
oropharyngeal pain
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 6 (33.33%)	0 / 2 (0.00%)	7 / 58 (12.07%)	3 / 52 (5.77%)
occurrences all number	2	0	7	3
paranasal sinus discomfort
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	0	0
productive cough
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences all number	1	0	1	0
rhinitis allergic
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	0 / 52 (0.00%)
occurrences all number	1	0	2	0
sleep apnoea syndrome
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	0	0
Psychiatric disorders
adjustment disorder with depressed mood
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	0	0
anxiety
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 6 (33.33%)	0 / 2 (0.00%)	4 / 58 (6.90%)	3 / 52 (5.77%)
occurrences all number	2	0	5	3
insomnia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 6 (33.33%)	1 / 2 (50.00%)	3 / 58 (5.17%)	4 / 52 (7.69%)
occurrences all number	2	1	3	4
Investigations
alanine aminotransferase increased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 6 (33.33%)	1 / 2 (50.00%)	25 / 58 (43.10%)	13 / 52 (25.00%)
occurrences all number	5	2	42	35
aspartate aminotransferase increased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	3 / 6 (50.00%)	0 / 2 (0.00%)	17 / 58 (29.31%)	10 / 52 (19.23%)
occurrences all number	5	0	28	22
blood alkaline phosphatase increased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	9 / 58 (15.52%)	7 / 52 (13.46%)
occurrences all number	2	0	12	7
blood creatinine increased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	1 / 52 (1.92%)
occurrences all number	1	0	2	1
blood urea increased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	0	1	0	0
ejection fraction decreased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	0	0
haemoglobin decreased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 58 (3.45%)	3 / 52 (5.77%)
occurrences all number	0	0	2	4
lymphocyte count decreased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 58 (3.45%)	3 / 52 (5.77%)
occurrences all number	0	0	3	5
neutrophil count decreased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	26 / 58 (44.83%)	29 / 52 (55.77%)
occurrences all number	0	1	76	92
platelet count decreased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	1 / 2 (50.00%)	21 / 58 (36.21%)	20 / 52 (38.46%)
occurrences all number	6	2	53	66
weight decreased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	3 / 52 (5.77%)
occurrences all number	0	0	2	5
white blood cell count decreased
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	3 / 6 (50.00%)	0 / 2 (0.00%)	20 / 58 (34.48%)	19 / 52 (36.54%)
occurrences all number	12	0	47	55
Injury, poisoning and procedural complications
infusion related reaction
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 6 (33.33%)	0 / 2 (0.00%)	7 / 58 (12.07%)	6 / 52 (11.54%)
occurrences all number	3	0	8	11
wrist fracture
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	1 / 52 (1.92%)
occurrences all number	2	0	0	1
Cardiac disorders
palpitations
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	6 / 58 (10.34%)	8 / 52 (15.38%)
occurrences all number	0	0	6	9
sinus bradycardia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	0	0
Nervous system disorders
dizziness
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 6 (33.33%)	0 / 2 (0.00%)	12 / 58 (20.69%)	9 / 52 (17.31%)
occurrences all number	2	0	13	9
dysgeusia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	5 / 58 (8.62%)	5 / 52 (9.62%)
occurrences all number	0	0	5	5
headache
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	3 / 6 (50.00%)	0 / 2 (0.00%)	10 / 58 (17.24%)	12 / 52 (23.08%)
occurrences all number	4	0	10	20
paraesthesia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	2 / 52 (3.85%)
occurrences all number	1	0	0	2
peripheral sensory neuropathy
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	5 / 58 (8.62%)	2 / 52 (3.85%)
occurrences all number	3	0	6	2
syncope
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 6 (33.33%)	0 / 2 (0.00%)	1 / 58 (1.72%)	0 / 52 (0.00%)
occurrences all number	2	0	1	0
tremor
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	6 / 58 (10.34%)	1 / 52 (1.92%)
occurrences all number	0	0	7	1
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	5 / 6 (83.33%)	1 / 2 (50.00%)	32 / 58 (55.17%)	25 / 52 (48.08%)
occurrences all number	8	4	91	73
increased tendency to bruise
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	3 / 58 (5.17%)	2 / 52 (3.85%)
occurrences all number	0	0	3	2
leukocytosis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	5 / 58 (8.62%)	0 / 52 (0.00%)
occurrences all number	0	0	8	0
leukopenia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 58 (3.45%)	3 / 52 (5.77%)
occurrences all number	0	0	3	4
neutropenia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	5 / 6 (83.33%)	2 / 2 (100.00%)	26 / 58 (44.83%)	26 / 52 (50.00%)
occurrences all number	24	4	72	74
thrombocytopenia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	4 / 6 (66.67%)	0 / 2 (0.00%)	17 / 58 (29.31%)	14 / 52 (26.92%)
occurrences all number	9	0	40	47
Ear and labyrinth disorders
tinnitus
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	4 / 58 (6.90%)	2 / 52 (3.85%)
occurrences all number	0	0	4	2
vertigo
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 6 (33.33%)	0 / 2 (0.00%)	2 / 58 (3.45%)	2 / 52 (3.85%)
occurrences all number	2	0	2	4
Eye disorders
glaucoma
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	0	0
vision blurred
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	3 / 58 (5.17%)	2 / 52 (3.85%)
occurrences all number	0	0	3	2
visual impairment
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 58 (1.72%)	3 / 52 (5.77%)
occurrences all number	1	0	1	3
Gastrointestinal disorders
abdominal discomfort
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	3 / 52 (5.77%)
occurrences all number	0	0	1	5
abdominal distension
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	6 / 58 (10.34%)	12 / 52 (23.08%)
occurrences all number	0	1	6	13
abdominal pain
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	12 / 58 (20.69%)	8 / 52 (15.38%)
occurrences all number	1	0	13	9
abdominal pain upper
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	5 / 58 (8.62%)	5 / 52 (9.62%)
occurrences all number	0	0	5	7
anal incontinence
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	1 / 52 (1.92%)
occurrences all number	1	0	0	1
constipation
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 6 (33.33%)	1 / 2 (50.00%)	23 / 58 (39.66%)	22 / 52 (42.31%)
occurrences all number	5	1	31	24
diarrhoea
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	4 / 6 (66.67%)	1 / 2 (50.00%)	23 / 58 (39.66%)	14 / 52 (26.92%)
occurrences all number	5	1	40	18
dry mouth
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 58 (3.45%)	4 / 52 (7.69%)
occurrences all number	0	0	2	4
dyspepsia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	3 / 58 (5.17%)	1 / 52 (1.92%)
occurrences all number	1	0	3	1
dysphagia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	2	0	0	0
gastrooesophageal reflux disease
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	3 / 58 (5.17%)	4 / 52 (7.69%)
occurrences all number	0	1	3	4
mouth ulceration
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 58 (3.45%)	3 / 52 (5.77%)
occurrences all number	0	0	2	4
nausea
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	4 / 6 (66.67%)	0 / 2 (0.00%)	31 / 58 (53.45%)	33 / 52 (63.46%)
occurrences all number	8	0	39	50
rectal haemorrhage
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 58 (0.00%)	4 / 52 (7.69%)
occurrences all number	0	0	0	5
stomatitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 6 (33.33%)	0 / 2 (0.00%)	9 / 58 (15.52%)	10 / 52 (19.23%)
occurrences all number	2	0	10	11
vomiting
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	3 / 6 (50.00%)	0 / 2 (0.00%)	17 / 58 (29.31%)	12 / 52 (23.08%)
occurrences all number	3	0	23	12
Skin and subcutaneous tissue disorders
alopecia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	10 / 58 (17.24%)	10 / 52 (19.23%)
occurrences all number	0	1	10	10
dry skin
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	3 / 58 (5.17%)	2 / 52 (3.85%)
occurrences all number	0	0	3	2
pruritus
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	7 / 58 (12.07%)	5 / 52 (9.62%)
occurrences all number	0	0	10	7
pruritus generalised
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	3 / 58 (5.17%)	2 / 52 (3.85%)
occurrences all number	0	0	3	2
rash
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	4 / 58 (6.90%)	3 / 52 (5.77%)
occurrences all number	0	0	5	6
Renal and urinary disorders
dysuria
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 58 (3.45%)	3 / 52 (5.77%)
occurrences all number	0	0	2	4
pollakiuria
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	3 / 52 (5.77%)
occurrences all number	0	0	1	3
urinary incontinence
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	4 / 52 (7.69%)
occurrences all number	0	0	1	4
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	6 / 58 (10.34%)	5 / 52 (9.62%)
occurrences all number	0	0	6	7
back pain
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	7 / 58 (12.07%)	12 / 52 (23.08%)
occurrences all number	1	0	10	13
bone pain
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	5 / 58 (8.62%)	1 / 52 (1.92%)
occurrences all number	0	0	5	2
flank pain
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	3 / 52 (5.77%)
occurrences all number	1	0	2	3
muscle spasms
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	3 / 58 (5.17%)	6 / 52 (11.54%)
occurrences all number	0	0	4	6
myalgia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	5 / 58 (8.62%)	5 / 52 (9.62%)
occurrences all number	0	0	5	6
neck pain
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	4 / 58 (6.90%)	0 / 52 (0.00%)
occurrences all number	0	0	4	0
osteoarthritis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	0	0
osteopenia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	0	0
pain in extremity
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	4 / 58 (6.90%)	3 / 52 (5.77%)
occurrences all number	1	0	7	3
Infections and infestations
bronchitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	3 / 52 (5.77%)
occurrences all number	0	0	2	3
cystitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	3 / 58 (5.17%)	0 / 52 (0.00%)
occurrences all number	0	0	3	0
fungal skin infection
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	0	0
nasopharyngitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	4 / 52 (7.69%)
occurrences all number	1	0	2	4
pneumonia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 58 (0.00%)	0 / 52 (0.00%)
occurrences all number	1	0	0	0
sinusitis
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	3 / 6 (50.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	2 / 52 (3.85%)
occurrences all number	4	0	1	2
upper respiratory tract infection
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	5 / 58 (8.62%)	3 / 52 (5.77%)
occurrences all number	0	0	6	3
urinary tract infection
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	8 / 58 (13.79%)	7 / 52 (13.46%)
occurrences all number	1	0	14	10
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	3 / 6 (50.00%)	0 / 2 (0.00%)	14 / 58 (24.14%)	12 / 52 (23.08%)
occurrences all number	3	0	15	13
dehydration
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 58 (1.72%)	1 / 52 (1.92%)
occurrences all number	1	0	1	1
hyperglycaemia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 58 (3.45%)	2 / 52 (3.85%)
occurrences all number	1	0	2	2
hyperkalaemia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 58 (1.72%)	3 / 52 (5.77%)
occurrences all number	0	0	4	3
hyperuricaemia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	2 / 58 (3.45%)	0 / 52 (0.00%)
occurrences all number	0	1	2	0
hypocalcaemia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 58 (3.45%)	4 / 52 (7.69%)
occurrences all number	0	0	4	4
hypokalaemia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	2 / 6 (33.33%)	0 / 2 (0.00%)	3 / 58 (5.17%)	4 / 52 (7.69%)
occurrences all number	2	0	5	7
hypomagnesaemia
alternative dictionary used: MedDRA 20.1
subjects affected / exposed	0 / 6 (0.00%)	1 / 2 (50.00%)	7 / 58 (12.07%)	5 / 52 (9.62%)
occurrences all number	0	1	11	14

More information

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Were there any global substantial amendments to the protocol? Yes

08 Jan 2014

Modification of dose limiting toxicity (DLT) criteria to account for expected toxicities with the combination of gemcitabine and carboplatin.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
25 Sep 2013	Enrollment was placed on hold to amend protocol to modify the dose limiting toxicity (DLT) criteria to account for expected toxicities from gemcitabine and carboplatin and to assess 300 mg LY2228820 in combination with gemcitabine and carboplatin.	-

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Study of LY2228820, a p38MAPK Inhibitor, plus Gemcitabine and Carboplatin versus Gemcitabine and Carboplatin for Women with Platinum-Sensitive Ovarian Cancer

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

Secondary: Phase 2: Overall Survival

Secondary: Phase 2: Overall Survival

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

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

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Hungary
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Ireland
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Outside EU/EEA

Clinical trials

Clinical Trial Results: A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Study of LY2228820, a p38MAPK Inhibitor, plus Gemcitabine and Carboplatin versus Gemcitabine and Carboplatin for Women with Platinum-Sensitive Ovarian Cancer

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

Secondary: Phase 2: Overall Survival

Secondary: Phase 2: Overall Survival

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

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

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Study of LY2228820, a p38MAPK Inhibitor, plus Gemcitabine and Carboplatin versus Gemcitabine and Carboplatin for Women with Platinum-Sensitive Ovarian Cancer