Axitinib (AG-013736) With Or Without Dose Titration (Incr... | NCT00835978

ID	Type	Description	Link
2008-007786-23	EudraCT Number

Label	Type	Description	Intervention Names
A	Other	Randomized arm	Drug: axitinib
B	Other	Randomized arm	Drug: axitinib
C	Other	Non-randomized arm	Drug: axitinib

Name	Type	Description	Arm Group Labels	Other Names
axitinib	Drug	axitinib 5mg BID (open-label) + axitinib dose titration (blinded)	A

Measure	Description	Time Frame
Objective Response Rate (ORR) - Percentage of Participants With Objective Response	ORR was defined as the proportion of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR was defined as complete disappearance of all target lesions and non-target disease. No new lesions. PR was defined as >=30% decrease on study under baseline of the sum of longest diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions.	Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks.

Measure	Description	Time Frame
Progression-Free Survival (PFS)	The time from first dose administration to first documentation of objective tumor progression or to death due to any cause. PFS in each arm was assessed using the Kaplan-Meier method and estimates of the PFS curves from the Kaplan-Meier method were presented.	Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks.

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

Facility	Status	City	State	ZIP	Country	Contacts
East Bay Medical Oncology/Hematology Medical Associates Inc.		Antioch	California	94531	United States

PubMed Identifier	Type	Citation	Retractions
30616534	Derived	Tomita Y, Uemura H, Oya M, Shinohara N, Habuchi T, Fujii Y, Kamei Y, Umeyama Y, Bair AH, Rini BI. Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study. BMC Cancer. 2019 Jan 7;19(1):17. doi: 10.1186/s12885-018-5224-6.
28410911	Derived

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

ID	Title	Description
FG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).

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

Objective Response Rate (ORR) - Percentage of Participants With Objective Response

ORR was defined as the proportion of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR was defined as complete disappearance of all target lesions and non-target disease. No new lesions. PR was defined as >=30% decrease on study under baseline of the sum of longest diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions.

The Full Analysis (FA) population included all randomized participants who received study drug or different drug to which they were randomized. The Safety Analysis (SA) population included all non-randomized patients who received at least 1 dose of study medication with treatment assignments designated according to actual study treatment received.

Posted

Number

95% Confidence Interval

Percentage of Participants

Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks.

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).
OG002	Non-randomized Arm	Participants not eligible for randomization were assigned to receive axitinib 5 mg BID or a reduced dose per the dose modification guideline. Dose titration was not permitted in this treatment arm.
OG003	All Participants	All enrolled participants (randomized and non-randomized)

Units	Counts
Participants	OG00056 OG00156 OG00291 OG003

Title

Denominators

Categories

Title	Measurements
	OG00053.6(39.7 to 67.0) OG00133.9(21.8 to 47.8) OG00259.3(48.5 to 69.5) OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	ORR for the 2 treatment arms was compared with the Cochran-Mantel-Haenszel test stratified by ECOG performance status. The relative risk ratio estimator was used to contrast the treatment effects on the endpoint. Both a point estimate and a 2-sided 95% CI were calculated using a normal approximation.	Cochran-Mantel-Haenszel		0.0189	A priori defined threshold for statistical significance was: alpha=0.10 (one-sided)	Risk Ratio (RR)	1.578			2-Sided	95	1.017	2.448					Superiority or Other

Secondary

Progression-Free Survival (PFS)

The time from first dose administration to first documentation of objective tumor progression or to death due to any cause. PFS in each arm was assessed using the Kaplan-Meier method and estimates of the PFS curves from the Kaplan-Meier method were presented.

Posted

Median

95% Confidence Interval

Months

Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks.

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

Duration of Response (DR)

DR was defined as the time from the first documentation of objective tumor response (complete response - CR or Partial response - PR) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. The median values were estimated based on Kaplan-Meier method. 95% confidence interval was based on the Brookmeyer and Crowley method.

Subset of Full Analysis (FA) and Safety Analysis (SA) patients who achieved confirmed complete or partial response. FA included all randomized patients and was based on randomized treatment assignment regardless of whether or not study drug was administered. SA included all non randomized patients who received at least one dose of study medication.

Posted

Median

95% Confidence Interval

Months

Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib(blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm

Secondary

Overall Survival (OS)

OS was defined as the time from date of the first dose of the study medication to date of death due to any cause. For participants who did not die, their survival times were to be censored at the last date they were known to be alive.

Posted

Median

95% Confidence Interval

Months

Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks.

ID	Title	Description
OG000	Active Titration Arm (FA Population)	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm (FA Population)	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

Maximum Observed Plasma Concentration (Cmax) of Axitinib

Cmax for steady-state axitinib was evaluated on Cycle 2 Day 15. Results were normalized to axitinib 7 mg dose for active titration arm and axitinib 5 mg dose for placebo titration arm. Results were normalized to axitinib 7 mg dose for active titration arm and axitinib 5 mg dose for placebo titration arm.

The pharmacokinetic (PK) population included all participants who were treated and had at least 1 concentration on 1 PK assessment day. The PK parameter analysis data set included all participants treated who had at least 1 estimated PK parameter of primary interest.

Posted

Geometric Mean

95% Confidence Interval

ng/mL

Cycle 2 Day 15 (C2D15): pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib(blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib,

Tmax for steady-state axitinib was evaluated on Cycle 2 Day 15.

Posted

Median

Full Range

hrs

C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib(blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Axitinib

Area under the plasma concentration time-curve from zero to the last measurable concentration (AUClast). AUClast for steady-state axitinib was evaluated on Cycle 2 Day 15. Results were normalized to axitinib 7 mg dose for active titration arm and axitinib 5 mg dose for placebo titration arm.

Posted

Geometric Mean

95% Confidence Interval

ng.hr/mL

C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

Area Under the Curve From Time Zero to 24 Hours[AUC(0-24)] for Axitinib

Area under the plasma concentration time-curve from zero 24 hours[AUC(0-24). AUC(0-24) for steady-state axitinib was evaluated on Cycle 2 Day 15. Results were normalized to axitinib 7 mg dose for active titration arm and axitinib 5 mg dose for placebo titration arm.](streamdown:incomplete-link)

Posted

Geometric Mean

95% Confidence Interval

ng.hr/mL

C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

Plasma Decay Half-Life (t1/2) for Axitinib

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Plasma decay half life for steady-state axitinib was evaluated on Cycle 2 Day 15.

Posted

Mean

Standard Deviation

C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib(blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo[blinded therapy] 5 mg BID).

Secondary

Apparent Oral Clearance (CL/F) of Axitinib

Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed (F). Clearance is defined as the volume of blood from which drug can be completely removed per unit of time. CL/F for steady-state axitinib was evaluated on Cycle 2 Day 15.

Posted

Geometric Mean

95% Confidence Interval

L/hr

C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib(blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

Apparent Volume of Distribution During the Elimination Phase (Vz/F) for Axitinib

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vz/F is influenced by the fraction absorbed. Vz/F for steady-state axitinb was evaluated on Cycle 2 Day 15.

Posted

Geometric Mean

95% Confidence Interval

C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib(blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo[blinded therapy] 5 mg BID).

Secondary

Change From Baseline in Systolic Blood Pressure

Value at respective visit minus value at baseline

The SA population consists of all participatns who received at least one dose of study medication.

Posted

Mean

Standard Deviation

mmHg

At screening (D-14 to D-1); lead-in period: Cycle 1 - Day 1 and Day 15; Cycle 2 - Day 1 and Day 15; Cycle 3 & subsequent cycles Day 1; end of study and follow-up 28 days after last dose.

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib(blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

Change From Baseline in Diastolic Blood Pressure

Value at respective visit minus value at baseline.

The SA population consists of all participatns who received at least one dose of study medication.

Posted

Mean

Standard Deviation

mmHg

At screening (D-14 to D-1); lead-in period: Cycle 1 - Day 1 and Day 15; Cycle 2 - Day 1 and Day 15; Cycle 3 & subsequent cycles Day 1; end of study and follow-up 28 days after last dose.

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

Comparison of Circulating Endothelial Cells (CECs) in Blood: Cluster of Differentiation (CD)146+/CD105+ at Baseline

CECs are noninvasive marker of vascular damage, remodeling, and dysfunction. Samples were collected and following proteins were analyzed: CD146+/CD105+ CECs, CD146+/CD105+ mean fluorescence intensity (MFI) platelet derived growth factor receptor (PDGFR)-beta, CD146+/CD105+ MFI phospho-PDGFR (pPDGFR)-beta, CD146+/CD105+ phospho-Vascular endothelial growth factor receptor (pVEGFR), CD146+/CD105+ MFI VEGFR. The ratio of plasma levels of the biomarkers at the selected time point vs baseline is reported.

The Biomarker Analysis Set included participants receiving at least one dose of treatment, with a Cycle 1 Day 1 biomarker result for at least one biomarker.

Posted

Mean

Standard Deviation

Fluorescent Intensity Unit (FIU)

At baseline - Beginning of the lead-in period (Cycle 1 Day 1)

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib(blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm

Secondary

Comparison of the Ratio of CECs in Blood: CD146+/CD105+ at Each Time Point to Baseline

CECs are noninvasive marker of vascular damage, remodeling, and dysfunction. Samples were collected and following proteins were analyzed: CD146+/CD105+ CECs, CD146+/CD105+ MFI platelet derived growth factor receptor (PDGFR)-beta, CD146+/CD105+ MFI phospho-PDGFR (pPDGFR)-beta, CD146+/CD105+ phospho-VEGFR (pVEGFR), CD146+/CD105+ MFI VEGFR. The ratio of plasma levels of the biomarkers at the selected time point vs baseline is reported.

The Biomarker Analysis Set included participants receiving at least one dose of treatment, with a Cycle 1 Day 1 biomarker result for at least one biomarker.

Posted

Mean

Standard Deviation

Ratio

At end of the lead-in period (Cycle 1 Day 15), Cycle 2 Day 15 and End of therapy (EOT)

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib(blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

Circulating Endothelial Cells (CECs) in Blood: CD31+/CD146+

CECs are noninvasive marker of vascular damage, remodeling, and dysfunction. Samples were collected and following proteins were analyzed: CD31+/CD146+ CECs, CD31+/CD146+ MFI PDGFR-beta, CD31+/CD146+ MFI pPDGFR-beta, CD31+/CD146+ pVEGFR, CD31+/CD146+ MFI VEGFR. The ratio of plasma levels of the biomarkers at the selected time point vs baseline is reported.

The Biomarker Analysis Set included participants receiving at least one dose of treatment, with a Cycle 1 Day 1 biomarker result for at least one biomarker.

Posted

Mean

Standard Deviation

Fluorescent Intensity Unit (FIU)

At baseline - Beginning of the lead-in period (Cycle 1 Day 1)

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

Comparison of Ratio of CECs in Blood: CD31+/CD146+ at Each Time Point to Baseline

The Biomarker Analysis Set included participants receiving at least one dose of treatment, with a Cycle 1 Day 1 biomarker result for at least one biomarker.

Posted

Mean

Standard Deviation

Ratio

At end of the lead-in period (Cycle 1 Day 15), Cycle 2 Day 15 and End of therapy (EOT)

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo[blinded therapy] 5 mg BID).

Secondary

ORR in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms

ORR, defined as proportion of participants with CR or PR according to RECIST, in subgroups that were defined by VEGFA or VEGFR3 polymorphisms.

The Safety Analysis (SA) population consisted of all participants who received at least one dose of study medication with treatment assignments designated according to actual study treatment received.

Posted

Number

95% Confidence Interval

Percentage of participants

At baseline - Beginning of the lead-in period (Cycle 1 Day 1)

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Secondary

PFS in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms

PFS, defined as the time from randomization to first documentation of objective tumor progression or to death due to any cause, in subgroups that were defined by VEGFA or VEGFR3 polymorphisms. Estimates of the PFS curves from the Kaplan-Meier method were presented.

Posted

Median

95% Confidence Interval

Months

At baseline - Beginning of the lead-in period (Cycle 1 Day 1)

ID	Title	Description
OG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
OG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG0030 affected10 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0022 affected91 at risk EG003
Coronary artery stenosis	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Diastolic dysfunction	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0010 affected56 at risk EG0022 affected91 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Cataract	Eye disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0023 affected91 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0011 affected56 at risk EG0021 affected91 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0011 affected56 at risk EG0021 affected91 at risk EG003
Diverticulum intestinal haemorrhagic	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0011 affected56 at risk EG0021 affected91 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0012 affected56 at risk EG0020 affected91 at risk EG003
Crohn's disease	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0021 affected91 at risk EG003
Gastrointestinal hypomotility	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Disease progression	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0011 affected56 at risk EG0026 affected91 at risk EG003
General physical health deterioration	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Chest pain	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Fatigue	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Pyrexia	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0012 affected56 at risk EG0021 affected91 at risk EG003
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Biliary colic	Hepatobiliary disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Cystitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Lung abscess	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Pneumonia	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0012 affected56 at risk EG0021 affected91 at risk EG003
Appendicitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Lung infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Peritonitis bacterial	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Postoperative wound infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Overdose	Injury, poisoning and procedural complications	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Postoperative hernia	Injury, poisoning and procedural complications	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Postoperative wound complication	Injury, poisoning and procedural complications	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Blood creatinine increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Blood sodium decreased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0005 affected56 at risk EG0010 affected56 at risk EG0023 affected91 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0011 affected56 at risk EG0022 affected91 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0021 affected91 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Haemarthrosis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Cerebrovascular insufficiency	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Syncope	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Headache	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0021 affected91 at risk EG003
Presyncope	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Somnolence	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Delirium	Psychiatric disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Renal colic	Renal and urinary disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Postrenal failure	Renal and urinary disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0022 affected91 at risk EG003
Pelvic prolapse	Reproductive system and breast disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Incisional hernia repair	Surgical and medical procedures	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Circulatory collapse	Vascular disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Hypertension	Vascular disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0021 affected91 at risk EG003
Hypertensive crisis	Vascular disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Hypotension	Vascular disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Gingivitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Incisional hernia	Injury, poisoning and procedural complications	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Postoperative ileus	Injury, poisoning and procedural complications	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Monoparesis	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Hypercapnia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.1	Non-systematic Assessment	EG0005 affected56 at risk EG0014 affected56 at risk EG0029 affected91 at risk EG0031 affected10 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0022 affected91 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 19.1	Non-systematic Assessment	EG00018 affected56 at risk EG00113 affected56 at risk EG00241 affected91 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0009 affected56 at risk EG0019 affected56 at risk EG00211 affected91 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0006 affected56 at risk EG0012 affected56 at risk EG00211 affected91 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG00011 affected56 at risk EG0017 affected56 at risk EG00227 affected91 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG00034 affected56 at risk EG00135 affected56 at risk EG00258 affected91 at risk EG003
Dry Mouth	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0007 affected56 at risk EG0012 affected56 at risk EG0027 affected91 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0007 affected56 at risk EG0015 affected56 at risk EG00218 affected91 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0007 affected56 at risk EG0013 affected56 at risk EG0024 affected91 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0011 affected56 at risk EG0024 affected91 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG00024 affected56 at risk EG00119 affected56 at risk EG00233 affected91 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG00010 affected56 at risk EG0014 affected56 at risk EG00217 affected91 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG00018 affected56 at risk EG00112 affected56 at risk EG00225 affected91 at risk EG003
Asthenia	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0006 affected56 at risk EG0015 affected56 at risk EG0026 affected91 at risk EG003
Fatigue	General disorders	MedDRA 19.1	Non-systematic Assessment	EG00027 affected56 at risk EG00126 affected56 at risk EG00249 affected91 at risk EG003
Mucosal inflammation	General disorders	MedDRA 19.1	Non-systematic Assessment	EG00012 affected56 at risk EG0018 affected56 at risk EG00213 affected91 at risk EG003
Rhinitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0016 affected56 at risk EG0024 affected91 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0006 affected56 at risk EG0019 affected56 at risk EG00212 affected91 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0006 affected56 at risk EG00110 affected56 at risk EG00212 affected91 at risk EG003
Blood creatinine increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0018 affected56 at risk EG00214 affected91 at risk EG003
Blood glucose increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0017 affected56 at risk EG00210 affected91 at risk EG003
Fibrin D dimer increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Weight decreased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG00016 affected56 at risk EG00112 affected56 at risk EG00225 affected91 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG00021 affected56 at risk EG00116 affected56 at risk EG00237 affected91 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0011 affected56 at risk EG0024 affected91 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG00013 affected56 at risk EG00111 affected56 at risk EG00217 affected91 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG00013 affected56 at risk EG0018 affected56 at risk EG00217 affected91 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0008 affected56 at risk EG0014 affected56 at risk EG00215 affected91 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0009 affected56 at risk EG0015 affected56 at risk EG00221 affected91 at risk EG003
Headache	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0009 affected56 at risk EG00115 affected56 at risk EG00227 affected91 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0010 affected56 at risk EG0024 affected91 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0005 affected56 at risk EG0013 affected56 at risk EG0023 affected91 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0011 affected56 at risk EG0020 affected91 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0014 affected56 at risk EG0028 affected91 at risk EG003
Haemoglobinuria	Renal and urinary disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0013 affected56 at risk EG0025 affected91 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 19.1	Non-systematic Assessment	EG00012 affected56 at risk EG00112 affected56 at risk EG00240 affected91 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0007 affected56 at risk EG0018 affected56 at risk EG00219 affected91 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG00018 affected56 at risk EG00120 affected56 at risk EG00244 affected91 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0006 affected56 at risk EG0018 affected56 at risk EG00227 affected91 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0007 affected56 at risk EG0013 affected56 at risk EG0027 affected91 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG00018 affected56 at risk EG00110 affected56 at risk EG00240 affected91 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0016 affected56 at risk EG00213 affected91 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0005 affected56 at risk EG0018 affected56 at risk EG00219 affected91 at risk EG003
Hypertension	Vascular disorders	MedDRA 19.1	Non-systematic Assessment	EG00035 affected56 at risk EG00124 affected56 at risk EG00276 affected91 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.1	Non-systematic Assessment	EG0005 affected56 at risk EG0013 affected56 at risk EG00215 affected91 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0013 affected56 at risk EG0023 affected91 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0012 affected56 at risk EG0029 affected91 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0013 affected56 at risk EG0026 affected91 at risk EG003
Oedema peripheral	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0013 affected56 at risk EG00214 affected91 at risk EG003
Pain	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0013 affected56 at risk EG0026 affected91 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0013 affected56 at risk EG0026 affected91 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0014 affected56 at risk EG0026 affected91 at risk EG003
Blood glucose decreased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0015 affected56 at risk EG0021 affected91 at risk EG003
Blood potassium increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0013 affected56 at risk EG0024 affected91 at risk EG003
Blood thyroid stimulating hormone increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0008 affected56 at risk EG0017 affected56 at risk EG0029 affected91 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0006 affected56 at risk EG0011 affected56 at risk EG0025 affected91 at risk EG003
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0027 affected91 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0010 affected56 at risk EG0029 affected91 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0011 affected56 at risk EG0022 affected91 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0012 affected56 at risk EG0024 affected91 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0012 affected56 at risk EG0025 affected91 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0012 affected56 at risk EG0022 affected91 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0014 affected56 at risk EG0023 affected91 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0013 affected56 at risk EG0028 affected91 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0014 affected56 at risk EG0025 affected91 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0008 affected56 at risk EG0019 affected56 at risk EG00223 affected91 at risk EG003
Dizziness	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0008 affected56 at risk EG00110 affected56 at risk EG00214 affected91 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0021 affected91 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0013 affected56 at risk EG00212 affected91 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0012 affected56 at risk EG0028 affected91 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0013 affected56 at risk EG00214 affected91 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0013 affected56 at risk EG0024 affected91 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0010 affected56 at risk EG0026 affected91 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0012 affected56 at risk EG0022 affected91 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0010 affected56 at risk EG0025 affected91 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0013 affected56 at risk EG0025 affected91 at risk EG003
Chest pain	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0005 affected56 at risk EG0012 affected56 at risk EG0026 affected91 at risk EG003
Chills	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0011 affected56 at risk EG0025 affected91 at risk EG003
General physical health deterioration	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Pyrexia	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0006 affected56 at risk EG0013 affected56 at risk EG0024 affected91 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0011 affected56 at risk EG0025 affected91 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0013 affected56 at risk EG00219 affected91 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0013 affected56 at risk EG0020 affected91 at risk EG003
Sinusitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0012 affected56 at risk EG0022 affected91 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0011 affected56 at risk EG00210 affected91 at risk EG003
Blood albumin decreased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0013 affected56 at risk EG0021 affected91 at risk EG003
Blood sodium decreased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0013 affected56 at risk EG0021 affected91 at risk EG003
Blood triglycerides increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0012 affected56 at risk EG0025 affected91 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0011 affected56 at risk EG0025 affected91 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0014 affected56 at risk EG0025 affected91 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0013 affected56 at risk EG0026 affected91 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0013 affected56 at risk EG0022 affected91 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0013 affected56 at risk EG0024 affected91 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0013 affected56 at risk EG0026 affected91 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0013 affected56 at risk EG0023 affected91 at risk EG003
Dyskinesia	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0011 affected56 at risk EG0023 affected91 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0013 affected56 at risk EG0027 affected91 at risk EG003
Delirium	Psychiatric disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0010 affected56 at risk EG0020 affected91 at risk EG003
Depression	Psychiatric disorders	MedDRA 19.1	Non-systematic Assessment	EG0004 affected56 at risk EG0014 affected56 at risk EG0026 affected91 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 19.1	Non-systematic Assessment	EG0003 affected56 at risk EG0010 affected56 at risk EG0023 affected91 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 affected56 at risk EG0012 affected56 at risk EG0026 affected91 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 affected56 at risk EG0014 affected56 at risk EG0025 affected91 at risk EG003
Tooth extraction	Surgical and medical procedures	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0013 affected56 at risk EG0021 affected91 at risk EG003
Hypotension	Vascular disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 affected56 at risk EG0018 affected56 at risk EG0029 affected91 at risk EG003

ID	Term
D002292	Carcinoma, Renal Cell
D007680	Kidney Neoplasms

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D014571	Urologic Neoplasms
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D007674	Kidney Diseases
D014570	Urologic Diseases
D052801	Male Urogenital Diseases

ID	Term
D001549	Benzamides
D000577	Amides
D009930	Organic Chemicals
D001565	Benzoates
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D007191	Indazoles
D011720	Pyrazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

ID	Title	Description
BG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
BG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).
BG002	Non-randomized Arm	Participants not eligible for randomization were assigned to receive axitinib 5 mg BID or a reduced dose per the dose modification guideline. Dose titration was not permitted in this treatment arm.
BG003	Discontinued Prior to Randomization	Participants who discontinued before they were randomized to any of the treatment or non-randomized arms.
BG004	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Active Titration Arm	Participants initially received axitinib 5 mg twice a day (BID) + axitinib(blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).	25	56	55	56
EG001	Placebo Titration Arm	Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator's clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).	14	56	51	56
EG002	Non-randomized Arm	Participants not eligible for randomization were assigned to receive axitinib 5 mg BID or a reduced dose per the dose modification guideline. Dose titration was not permitted in this treatment arm.	39	91	91	91
EG003	Discontinued Prior to Randomization	Participants who were discontinued prior to randomization to either treatment or non-randomization arms.	2	10	9	10