Study of PF-05212384 (Also Known as PKI-587)Administered... | NCT00940498

ID	Type	Description	Link
3265K1-1002	Other Identifier	Alias Study Number
2009-012379-85	EudraCT Number

Label	Type	Description	Intervention Names
1	Experimental	PF-05212384 (also known as PKI-587)	Drug: PF-05212384 (also known as PKI-587)

Name	Type	Description	Arm Group Labels	Other Names
PF-05212384 (also known as PKI-587)	Drug	Intravenous dosing once weekly infusion	1

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.	Baseline up to Cycle 14 (each cycle is 28 days)
Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) or Serious Adverse Events (SAEs)	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pretreatment state. Relatedness to drug was assessed by the investigator. Participants with multiple occurrences of an AE within a category were counted once within the category. AEs included both serious and non-serious adverse events.	Baseline up to Cycle 14 (each cycle is 28 days)
Number of Participants With Laboratory Abnormalities	Criteria for laboratory test abnormality: hematology (hemoglobin [less than {<} 0.8lower limit of normal {LLN}], platelets [<0.5LLN or greater than {>} 1.75upper limit of normal {ULN}], white blood cells [<0.6LLN or >1.5ULN], lymphocytes [<0.8LLN or >1.2ULN], total neutrophils [<0.8LLN or >1.2ULN], basophils, eosinophils, monocytes [>1.2ULN]); coagulation [partial thromboplastin time, prothrombin (PT), PT international ratio [>1.1ULN]); liver function (total bilirubin [>1.5ULN], aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase [>0.3ULN], total protein, albumin [<0.8LLN or >1.2*ULN]).](streamdown:incomplete-link)

Measure	Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of PF-05212384: Single and Multiple Dose		Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05212384: Single Dose

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Massachusetts General Hospital		Boston	Massachusetts	02114	United States
Beth Israel Deaconess Medical Center

PubMed Identifier	Type	Citation	Retractions
25652454	Derived	Shapiro GI, Bell-McGuinn KM, Molina JR, Bendell J, Spicer J, Kwak EL, Pandya SS, Millham R, Borzillo G, Pierce KJ, Han L, Houk BE, Gallo JD, Alsina M, Brana I, Tabernero J. First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95. doi: 10.1158/1078-0432.CCR-14-1306. Epub 2015 Feb 4.

Label	URL
To obtain contact information for a study center near you, click here.	View source

ID	Title	Description
FG000	Part 1: PF-05212384 10 mg	PF-05212384 10 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
FG001	Part 1: PF-05212384 21 mg

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.

Safety analysis set included all participants who received at least 1 dose of study medication.

Posted

Count of Participants

Participants

Baseline up to Cycle 14 (each cycle is 28 days)

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG002	Part 1: PF-05212384 43 mg	PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG003	Part 1: PF-05212384 89 mg	PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG004	Part 1 and 2: PF-05212384 154 mg	PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
OG005	Part 1: PF-05212384 222 mg	PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG006	Part 1: PF-05212384 266 mg	PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG007	Part 1: PF-05212384 319 mg	PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.

Units	Counts
Participants	OG0004 OG0014 OG0024 OG003

Title

Denominators

Categories

AEs

Title	Measurements
	OG0004 OG0014 OG0024 OG003

Primary

Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) or Serious Adverse Events (SAEs)

Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pretreatment state. Relatedness to drug was assessed by the investigator. Participants with multiple occurrences of an AE within a category were counted once within the category. AEs included both serious and non-serious adverse events.

Safety analysis set included all participants who received at least 1 dose of study medication.

Posted

Count of Participants

Participants

Baseline up to Cycle 14 (each cycle is 28 days)

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.

Primary

Number of Participants With Laboratory Abnormalities

Criteria for laboratory test abnormality: hematology (hemoglobin [less than {<} 0.8*lower limit of normal {LLN}], platelets [<0.5*LLN or greater than {>} 1.75*upper limit of normal {ULN}], white blood cells [<0.6*LLN or >1.5*ULN], lymphocytes [<0.8*LLN or >1.2*ULN], total neutrophils [<0.8*LLN or >1.2*ULN], basophils, eosinophils, monocytes [>1.2*ULN]); coagulation [partial thromboplastin time, prothrombin (PT), PT international ratio [>1.1*ULN]); liver function (total bilirubin [>1.5*ULN], aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase [>0.3*ULN], total protein, albumin [<0.8*LLN or >1.2*ULN]).](streamdown:incomplete-link)

Safety analysis set included all participants who received at least 1 dose of study medication.

Posted

Count of Participants

Participants

Baseline up to Cycle 14 (each cycle is 28 days)

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.

Primary

Number of Participants With Dose Limiting Toxicities (DLTs)

DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: Grade 3 nonhematologic AE (including nausea, vomiting, or diarrhea despite optimal therapy; or greater than or equal to [>=] grade 3 asthenia >2 days; or fasting serum glucose >250 milligrams per deciliter (mg/dL) despite optimal therapy); >=Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 neutropenia lasting more than 7 days; Febrile neutropenia; other Grade 4 hematologic AE; delay of treatment >2 consecutive weeks due to toxicity. Grades were based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

DLT evaluable analysis set included all enrolled participants who started treatment and did not have had a major treatment deviation in the first cycle of treatment.

Posted

Count of Participants

Participants

Baseline up to Day 28

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.

Primary

Recommended Phase-2 Dose (RP2D)

RP2D of PF-05212384 was determined based on the safety profile including laboratory and clinical assessments and pharmacodynamics findings.

Safety analysis population included all participants who received at least 1 dose of study medication.

Posted

Number

Baseline up to Cycle 14 (each cycle is 28 days)

ID	Title	Description
OG000	PF-05212384 : All Participants	All participants who received PF-05212384 10 mg or 21 mg or 43 mg or 89 mg or 154 mg or 222 mg or 266 mg or 319 mg, intravenous infusion, once weekly in each 28 day cycle until progression of disease, uncontrollable toxicity, or a decision by the participant or investigator to discontinue.

Units	Counts
Participants	OG000

Secondary

Maximum Observed Plasma Concentration (Cmax) of PF-05212384: Single and Multiple Dose

PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter (ng/mL)

Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG002	Part 1: PF-05212384 43 mg	PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.

Secondary

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05212384: Single Dose

Area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (Clast).

PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram*hour per milliliter(ng*hr/mL)

Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG002	Part 1: PF-05212384 43 mg

Secondary

Plasma Decay Half-Life (t1/2) of PF-05212384: Single and Multiple Dose

Plasma decay half-life is the time measured for the plasma concentration of drug to decrease by one half.

PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated.

Posted

Mean

Standard Deviation

hours (hr)

Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG002	Part 1: PF-05212384 43 mg	PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.

Secondary

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-05212384: Single Dose

AUCinf= Area under the plasma concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - inf).

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*hr/mL

Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG002	Part 1: PF-05212384 43 mg

Secondary

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05212384: Single and Multiple Dose

Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 168 hours (1 Week). For Cycle 2, the last PK sample for parameter calculations was on 120 hours after the Day 1 dose, however AUCtau was extrapolated to 168 hours using t1/2.

PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*hr/mL

Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG002

Secondary

Number of Participants With Maximum Increase From Baseline in Corrected QT Interval

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Number of Participants with maximum increase from baseline in QTcB and QTcF of < 30 msec, between <=30 to <60 msec and >=60 were reported.

The QTc analysis set included all enrolled participants who had at least one ECG assessment after receiving PF-05212384

Posted

Count of Participants

Participants

Baseline up to Cycle 14 (each cycle is 28 days)

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.

Secondary

Change From Baseline in Serum Glucose at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment

Serum biomarker analysis set included all enrolled participants who started treatment and had baseline and on-treatment serum biomarker samples successfully analyzed for at least 1 biomarker.

Posted

Mean

Standard Deviation

milligram per deciliter (mg/dL)

Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG002	Part 1: PF-05212384 43 mg	PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.

Secondary

Change From Baseline in Serum Insulin at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment

Serum biomarker analysis set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure (OM).

Posted

Mean

Standard Deviation

microunits per milliliter (mcU/mL)

Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)

ID	Title	Description
OG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG002	Part 1: PF-05212384 43 mg	PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.

Secondary

Change From Baseline in Serum C-peptide at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment

Serum biomarker analysis set. Here, N= participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for reporting arms: PF-05212384 10 mg, 21 mg, 43 mg, 89 mg, and 319 mg, as pre specified in protocol Amendment 5.

Posted

Mean

Standard Deviation

ng/mL

Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)

ID	Title	Description
OG000	Part 1 and 2: PF-05212384 154 mg	PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
OG001	Part 1: PF-05212384 222 mg	PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG002	Part 1: PF-05212384 266 mg	PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.

Secondary

Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 1

Analysis of hair follicles was conducted using a Reverse Phase Microarrays (RPMA) assay. Phosphoprotein biomarkers measured were pAkt S473, pAkt T308, pStat3 (Y705), Ki-67, and pPRAS40 (T246).

Hair follicle analysis set. Here, N= participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for reporting arms: PF-05212384 10 mg, 21 mg, 43 mg, 89 mg, and 319 mg, as pre specified in protocol Amendment 5.

Posted

Mean

Standard Deviation

normalized fluorescence units (NFU)

Baseline, 2, 3 and 72 hours (H) postdose on Day 1 of Cycle 1

ID	Title	Description
OG000	Part 1 and 2: PF-05212384 154 mg	PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
OG001	Part 1: PF-05212384 222 mg	PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
OG002	Part 1: PF-05212384 266 mg

Secondary

Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 22

Tumor biopsies were taken from participants of reporting arm PF-05212384 154 mg dose level at baseline and at Cycle 1/Day 22. Biopsies were fixed in optimal cutting temperature compound and analyzed via RPMA. The biomarkers tested were phosphorylated versions of the proteins: AKT S473, AKT T308, FKHR T24 / FKHR1 T32, and STAT3. This outcome measure was planned to be analyzed only for the reporting arm Part 1 and 2: PF-05212384 154 mg, as pre-specified in protocol.

Tumor biopsy analysis set=all enrolled participants who had treatment &had baseline,on-treatment tumor tissue successfully analyzed for at least 1 biomarker.N=participants evaluable for this OM. This OM was planned to analyzed only in reporting arm- Part 1 and 2:PF-05212384 154 mg.

Posted

Mean

Standard Deviation

normalized to cytokeratin (NFC)

Baseline, Day 22 of Cycle 1

ID	Title	Description
OG000	Part 1 and 2: PF-05212384 154 mg	PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.

Units	Counts
Participants

Secondary

Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue

Biopsied tumor tissue was analyzed for alterations in the phosphoinositide-3-kinase/rat sarcoma (PI3K/RAS) signaling pathway by molecular approaches. The biomarkers studied were PIK3CA and phosphatase and tensin homolog (PTEN) by immunohistochemistry.

Baseline tumor tissue biomarker analysis set: All enrolled patients who start treatment and had baseline tumor tissues successfully analyzed for at least one of the biomarkers. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Posted

Count of Participants

Participants

Baseline

ID	Title	Description
OG000	PF-05212384 : All Participants	PF-05212384-10,21,43,89,154,222,266,319 milligram (mg) intravenous infusion over approximately 30 minutes once weekly in each 28 day cycle until progression of disease, uncontrollable toxicity, or a decision by the patient or investigator to discontinue.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Objective Response (OR)

Objective response was defined as having complete response (CR) or Partial Response (PR) assessed by RECIST 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). Percentage of participants with objective response were reported.

Response-evaluable population included participants who received at least 1 dose of study drug, had an adequate baseline tumor assessment and at least 1 post baseline disease assessment for analyses of response.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline until disease progression or death due to any cause (up to Cycle 14 [each cycle 28 days])

ID	Title	Description
OG000	PF-05212384 : All Participants	Entire study population treated with PF-05212384-10,21,43,89,154,222,266,319 mg intravenous infusion over approximately 30 minutes once weekly in each 28 day cycle until progression of disease, uncontrollable toxicity, or a decision by the participant or investigator to discontinue.

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0021 affected4 at risk EG0031 affected4 at risk EG0046 affected42 at risk EG0051 affected7 at risk EG0062 affected8 at risk EG0072 affected4 at risk
Hypochromic anaemia	Blood and lymphatic system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Cerumen impaction	Ear and labyrinth disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hearing impaired	Ear and labyrinth disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Blepharitis	Eye disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Cataract	Eye disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Conjunctivitis	Eye disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Diplopia	Eye disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Eyelid oedema	Eye disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Vision blurred	Eye disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Anal pruritus	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Gastric varices	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Gastrointestinal hypomotility	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Gingival inflammation	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Glossitis	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypoaesthesia oral	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0003 affected4 at risk EG0012 affected4 at risk EG0022 affected4 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Oral discomfort	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Oral dysaesthesia	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Oral mucosal erythema	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Painful defaecation	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Paraesthesia oral	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Perianal erythema	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Proctitis	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Rectal discharge	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Rectal ulcer	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Tongue coated	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Tooth loss	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Varices oesophageal	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0003 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Asthenia	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Catheter site pain	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Catheter site rash	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Chest pain	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Chills	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Early satiety	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Face oedema	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Facial pain	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Fatigue	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0003 affected4 at risk EG0012 affected4 at risk EG0022 affected4 at risk EG003
Feeling jittery	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Influenza like illness	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Infusion site reaction	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Injection site reaction	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Localised oedema	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Malaise	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Mucosal inflammation	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0021 affected4 at risk EG003
Oedema peripheral	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0002 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Pain	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0021 affected4 at risk EG003
Performance status decreased	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Pyrexia	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0012 affected4 at risk EG0020 affected4 at risk EG003
Sensation of foreign body	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Thirst	General disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Bile duct obstruction	Hepatobiliary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hepatic pain	Hepatobiliary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Candidiasis	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Cystitis	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Device related infection	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Enterocolitis infectious	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Folliculitis	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Fungal infection	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Laryngitis	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Lip infection	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Localised infection	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Oral herpes	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Rhinitis	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Sputum purulent	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Tinea pedis	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Vaginal infection	Infections and infestations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Ear injury	Injury, poisoning and procedural complications	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Activated partial thromboplastin time prolonged	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0002 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Amylase increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Blood albumin decreased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0003 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Blood calcium decreased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Blood cholesterol increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Blood creatinine increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Blood magnesium decreased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Blood potassium decreased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Blood sodium decreased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Breath sounds abnormal	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Glycosylated haemoglobin increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Heart rate increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
International normalised ratio increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Liver palpable subcostal	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Pancreatic enzymes increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Platelet count decreased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Transaminases increased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Weight decreased	Investigations	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Acidosis	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Cachexia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0002 affected4 at risk EG0011 affected4 at risk EG0022 affected4 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Fluid overload	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Glucose tolerance impaired	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hyperamylasaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0022 affected4 at risk EG003
Hyperchloraemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hyperlipasaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Hypophagia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Inguinal mass	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Aphasia	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Brain oedema	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Convulsion	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Dizziness	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Dizziness postural	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Dysaesthesia	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Headache	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hemianopia	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypersomnia	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Intracranial pressure increased	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Motor dysfunction	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Neuralgia	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Presyncope	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Somnolence	Nervous system disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Nervousness	Psychiatric disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Oliguria	Renal and urinary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Polyuria	Renal and urinary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Renal vein thrombosis	Renal and urinary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Scrotal swelling	Reproductive system and breast disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Testicular pain	Reproductive system and breast disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Vaginal discharge	Reproductive system and breast disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0012 affected4 at risk EG0020 affected4 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0021 affected4 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Pharyngeal erythema	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Rhonchi	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Upper respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Cutaneous lupus erythematosus	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected4 at risk EG003
Onychoclasis	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Papule	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Peau d'orange	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0022 affected4 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected4 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Flushing	Vascular disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Haemorrhage	Vascular disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypertension	Vascular disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Hypotension	Vascular disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Lymphoedema	Vascular disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Pallor	Vascular disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Phlebitis	Vascular disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003
Thrombophlebitis superficial	Vascular disorders	MedDRA 15.1	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected4 at risk EG003

ID	Title	Description
BG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
BG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
BG002	Part 1: PF-05212384 43 mg	PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
BG003	Part 1: PF-05212384 89 mg	PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
BG004	Part 1 and 2: PF-05212384 154 mg	PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
BG005	Part 1: PF-05212384 222 mg	PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
BG006	Part 1: PF-05212384 266 mg	PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
BG007	Part 1: PF-05212384 319 mg	PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
BG008	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1: PF-05212384 10 mg	PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.	2	4	4	4
EG001	Part 1: PF-05212384 21 mg	PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.	1	4	4	4
EG002	Part 1: PF-05212384 43 mg	PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.	1	4	4	4
EG003	Part 1: PF-05212384 89 mg	PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.	1	4	4	4
EG004	Part 1 and 2: PF-05212384 154 mg	PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.	16	42	42	42
EG005	Part 1: PF-05212384 222 mg	PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.	0	7	7	7
EG006	Part 1: PF-05212384 266 mg	PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.	5	8	8	8
EG007	Part 1: PF-05212384 319 mg	PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.	2	4	4	4