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Clinical Trial Results:
A Phase 1b (Open-Label) / Phase 2 (Randomized, Double-Blinded) Study Evaluating Gemcitabine and Docetaxel With or Without Olaratumab in the Treatment of Advanced Soft Tissue Sarcoma

Summary
EudraCT number	2015-001316-34
Trial protocol	HU ES DE PL GB IT
Global end of trial date	27 Apr 2021

Results information
Results version number	v2(current)
This version publication date	01 May 2022
First version publication date	11 Aug 2021
Other versions	v1
Version creation reason	New data added to full data set LPV results

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

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Trial information

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Sponsor protocol code

I5B-MC-JGDL

ISRCTN number

US NCT number

NCT02659020

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 15839

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

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

Scientific contact

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

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

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

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

Analysis stage

Final

Date of interim/final analysis

28 Jul 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

27 Apr 2021

Was the trial ended prematurely?

Main objective of the trial

The main purpose of this study is to evaluate the safety and efficacy of two anti-cancer drugs (gemcitabine and docetaxel) with and without the study drug known as olaratumab in participants with advanced soft tissue sarcoma (STS) or STS that has spread to another part(s) of the body.

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Mar 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 9

Country: Number of subjects enrolled

Germany: 24

Country: Number of subjects enrolled

Spain: 37

Country: Number of subjects enrolled

Hungary: 11

Country: Number of subjects enrolled

United States: 161

Country: Number of subjects enrolled

Poland: 8

Country: Number of subjects enrolled

United Kingdom: 31

Country: Number of subjects enrolled

Italy: 6

Country: Number of subjects enrolled

Israel: 18

Country: Number of subjects enrolled

France: 5

Worldwide total number of subjects

310

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

227

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

No Text Available

Screening details

Completers included participants who died from any cause.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

Phase 1b (Open-Label), Phase 2 (Double-Blinded)

Are arms mutually exclusive

Yes

Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel

Arm description

Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Arm type

Experimental

Investigational medicinal product name

Olaratumab

Investigational medicinal product code

Other name

LY3012207,IMC-3G3

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of olaratumab 15 mg/kg on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

LY188011,Gemzar

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of gemcitabine 900 mg/m^2 on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Phase1b:Cohort2: 20mg/kg Olaratumab+Gemcitabine+Docetaxel

Arm description

Arm type

Experimental

Investigational medicinal product name

Olaratumab

Investigational medicinal product code

Other name

LY3012207,IMC-3G3

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of olaratumab 20 mg/kg on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

LY188011,Gemzar

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of gemcitabine 900 mg/m^2 on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Phase1b:Cohort2Expand:20mg/kgOlaratumab+Gemcitabine+Docetaxel

Arm description

Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2. Participants received intravenous infusions of olaratumab 20 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Arm type

Experimental

Investigational medicinal product name

Olaratumab

Investigational medicinal product code

Other name

LY3012207,IMC-3G3

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of olaratumab 20 mg/kg on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

LY188011,Gemzar

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of gemcitabine 900 mg/m^2 on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)

Arm description

This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Arm type

Experimental

Investigational medicinal product name

Olaratumab

Investigational medicinal product code

Other name

LY3012207,IMC-3G3

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

LY188011,Gemzar

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of gemcitabine 900 mg/m^2 on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)

Arm description

This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Arm type

Experimental

Investigational medicinal product name

Olaratumab

Investigational medicinal product code

Other name

LY3012207,IMC-3G3

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

LY188011,Gemzar

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of gemcitabine 900 mg/m^2 on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Arm description

This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of placebo on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

LY188011,Gemzar

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of gemcitabine 900 mg/m^2 on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Arm description

This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of placebo on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

LY188011,Gemzar

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of gemcitabine 900 mg/m^2 on days 1, 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous infusions of docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Number of subjects in period 1	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2: 20mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2Expand:20mg/kgOlaratumab+Gemcitabine+Docetaxel	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)
Started	21	18	15	81	46	86	43
Received atLeast 1 Doseof Study Drug	21	18	15	81	45	86	43
Completed	18	15	14	65	40	75	35
Not completed	3	3	1	16	6	11	8
Consent withdrawn by subject	2	1	-	3	3	-	3
Physician decision	-	-	-	1	1	-	1
Adverse event, non-fatal	-	-	-	2	-	6	2
Progressive Disease	-	-	-	4	1	-	2
Lost to follow-up	1	2	1	6	1	5	-

Baseline characteristics

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Reporting group title

Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel

Reporting group description

Reporting group title

Phase1b:Cohort2: 20mg/kg Olaratumab+Gemcitabine+Docetaxel

Reporting group description

Reporting group title

Phase1b:Cohort2Expand:20mg/kgOlaratumab+Gemcitabine+Docetaxel

Reporting group description

Reporting group title

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)

Reporting group description

Reporting group title

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)

Reporting group description

Reporting group title

Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Reporting group description

Reporting group title

Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Reporting group description

Reporting group values	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2: 20mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2Expand:20mg/kgOlaratumab+Gemcitabine+Docetaxel	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)	Total
Number of subjects	21	18	15	81	46	86	43	310
Age categorical
Units: Subjects
<65 years	20	12	6	66	27	66	30	227
>=65 years	1	6	9	15	19	20	13	83
<=18 years	0	0	0	0	0	0	0	0
Gender categorical
Units: Subjects
Female	11	8	7	48	28	58	28	188
Male	10	10	8	33	18	28	15	122
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	5	0	1	8	4	6	4	28
Not Hispanic or Latino	16	18	11	71	39	73	36	264
Unknown or Not Reported	0	0	3	2	3	7	3	18
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	1	0	0	0	0	1
Asian	0	1	1	3	2	2	2	11
Native Hawaiian or Other Pacific Islander	0	0	0	0	1	0	0	1
Black or African American	0	2	0	1	8	1	2	14
White	15	10	13	61	30	70	34	233
More than one race	6	5	0	15	3	10	3	42
Unknown or Not Reported	0	0	0	1	2	3	2	8
Region of Enrollment
Units: Subjects
Hungary	0	0	0	5	0	6	0	11
United States	10	14	14	29	36	28	30	161
Poland	0	0	0	6	0	2	0	8
United Kingdom	0	0	0	11	3	12	5	31
Italy	0	0	0	2	0	4	0	6
Israel	0	0	0	4	3	7	4	18
France	0	0	0	2	0	3	0	5
Australia	0	0	1	6	0	2	0	9
Germany	0	0	0	7	4	11	2	24
Spain	11	4	0	9	0	11	2	37

End points

Top of page

Reporting group title

Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel

Reporting group description

Reporting group title

Phase1b:Cohort2: 20mg/kg Olaratumab+Gemcitabine+Docetaxel

Reporting group description

Reporting group title

Phase1b:Cohort2Expand:20mg/kgOlaratumab+Gemcitabine+Docetaxel

Reporting group description

Reporting group title

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)

Reporting group description

Reporting group title

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)

Reporting group description

Reporting group title

Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Reporting group description

Reporting group title

Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Reporting group description

Subject analysis set title

Phase1b:Cohort2overall-20mg/kgOlaratumab+Gemcitabine+Docetaxel

Subject analysis set type

Per protocol

Subject analysis set description

Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met (cohort 2). Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 (cohort 2 expansion).

Subject analysis set title

Phase2:Olaratumab+Gemcitabine+Docetaxel

Subject analysis set type

Per protocol

Subject analysis set description

Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.

Subject analysis set title

Phase2:Placebo+Gemcitabine+Docetaxel

Subject analysis set type

Per protocol

Subject analysis set description

Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.

Subject analysis set title

Olaratumab + Gemcitabine + Docetaxel

Subject analysis set type

Per protocol

Subject analysis set description

Participants received intravenous infusions of olaratumab on days 1, 8 (phase 1: 15 or 20 mg/kg; phase 2: 20 mg/kg only in cycle 1 and 15 mg/kg in subsequent cycles) plus gemcitabine 900 mg/m^2 on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Primary: Phase 1b: Number of Participants with Dose Limiting Toxicity (DLT)

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End point title

Phase 1b: Number of Participants with Dose Limiting Toxicity (DLT) ^[1] ^[2]

End point description

A Dose Limiting Toxicity is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE Version 4.0: 1. Febrile neutropenia with documented Grade ≥3 infection or sepsis 2. Grade 4 neutropenia lasting 7 days or longer. 3. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage. 4. Nonhematologic Grade ≥3 toxicity, except for toxicities such as nausea, vomiting, transient electrolyte abnormalities, or diarrhoea that can be controlled with optimal medical management within 48 hours. Analysis Population Description: Phase 1b: All participants who received at least one dose of Olaratumab.

End point type

Primary

End point timeframe

Cycle 1 (Up To 21 Days)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No inferential statistics were planned for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 1b participants.

End point values	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2: 20mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2Expand:20mg/kgOlaratumab+Gemcitabine+Docetaxel
Number of subjects analysed	21	18	15
Units: participants	1	4	3

No statistical analyses for this end point

Primary: Phase 2: Overall Survival (OS) (Olaratumab-Naive)

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End point title

Phase 2: Overall Survival (OS) (Olaratumab-Naive) ^[3]

End point description

OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact. Analysis Population Description: Phase 2: All randomized participants (including the censored participants). Number of participants censored in "Olaratumab+ Gemcitabine+Docetaxel(Olaratumab-naive)=30," "Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)=28."

End point type

Primary

End point timeframe

Baseline to Date of Death Due to Any Cause (Up To 38 Months)

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 2 Olaratumab-Naive participants.

End point values	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)
Number of subjects analysed	81	86
Units: Months
median (confidence interval 95%)	16.76 (15.28 to 25.40)	18.04 (13.17 to 22.90)

Statistical analysis 1

Comparison groups

Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.775 ^[4]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.945

Confidence interval

level

95%

sides

2-sided

lower limit

0.639

upper limit

1.397

Notes
[4] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 vs1).

Secondary: Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab

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End point title

Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab ^[5]

End point description

Cmax of Olaratumab. Analysis Population Description: Phase 1b: All participants who received at least one dose of Olaratumab and had evaluable PK data.

End point type

Secondary

End point timeframe

Pre-dose, 5 minutes (min), 1, 4, 4.5, 24, 96, 168, 336 hours (h) post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 1b participants.

End point values	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2overall-20mg/kgOlaratumab+Gemcitabine+Docetaxel
Number of subjects analysed	20 ^[6]	33 ^[7]
Units: micrograms per milliliter (μg/mL)
geometric mean (geometric coefficient of variation)
Cycle 1 (Day 1)	432 ( 24 )	572 ( 25 )
Cycle 1 (Day 8)	460 ( 25 )	697 ( 20 )
Cycle 3 (Day 1)	523 ( 38 )	644 ( 20 )
Cycle 3 (Day 8)	513 ( 21 )	689 ( 20 )

Notes
[6] - Cycle 1 (Day 1) = 19; Cycle 3 (Day 1), Cycle 3 (Day 8) = 14
[7] - Cycle 3 (Day 1) = 23; Cycle 3 (Day 8) = 22

No statistical analyses for this end point

Secondary: Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab

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End point title

Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab ^[8]

End point description

Cmin of Olaratumab. Analysis Population Description: Phase 1b: All participants who received at least one dose of Olaratumab and had evaluable PK data.

End point type

Secondary

End point timeframe

Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 1b participants.

End point values	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2overall-20mg/kgOlaratumab+Gemcitabine+Docetaxel
Number of subjects analysed	20 ^[9]	31 ^[10]
Units: μg/mL
geometric mean (geometric coefficient of variation)
Cycle 1 (Day 1)	95.9 ( 37 )	142 ( 38 )
Cycle 1 (Day 8)	64.3 ( 64 )	93.3 ( 47 )
Cycle 3 (Day 1)	137 ( 40 )	252 ( 36 )

Notes
[9] - Cycle 1 (Day 8) = 19; Cycle 3 (Day 1) = 14
[10] - Cycle 1 (Day 8) = 30; Cycle 3 (Day 1) = 22

No statistical analyses for this end point

Secondary: Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab

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End point title

Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab ^[11]

End point description

T1/2 of Olaratumab. Analysis Population Description: Phase 1b: All participants who received at least one dose of Olaratumab and had evaluable PK data.

End point type

Secondary

End point timeframe

Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 1b participants.

End point values	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2overall-20mg/kgOlaratumab+Gemcitabine+Docetaxel
Number of subjects analysed	19 ^[12]	33 ^[13]
Units: days
geometric mean (geometric coefficient of variation)
Cycle 1 (Day 1)	4.60 ( 34 )	4.29 ( 28 )
Cycle 1 (Day 8)	6.25 ( 25 )	6.62 ( 27 )
Cycle 3 (Day 1)	5.17 ( 36 )	6.36 ( 41 )
Cycle 3 (Day 8)	5.82 ( 30 )	6.39 ( 32 )

Notes
[12] - Cycle 3 (Day 1), Cycle 3 (Day 8) = 14
[13] - Cycle 3 (Day 1) = 23; Cycle 3 (Day 8) = 21

No statistical analyses for this end point

Secondary: Phase 1b/2: PK: Cmax of Gemcitabine

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End point title

Phase 1b/2: PK: Cmax of Gemcitabine ^[14]

End point description

Cmax of Gemcitabine. Analysis Population Description: Phase 1b/2: All participants who received at least one dose of Gemcitabine and had evaluable PK data.

End point type

Secondary

End point timeframe

Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcomes were reported by combining phase 1b cohort 2+cohort2expand arms [i.e. Cohort2overall:20mg/kgOlaratumab+Gemcitabine+Docetaxel]; Phase2Olaratumab+Gemcitabine+Docetaxel (Olaratumab-naive) +Phase2Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) arms [i.e.Phase2: Olaratumab+Gemcitabine+Docetaxel]; Phase2Placebo+Gemcitabine+Docetaxel (Olaratumab-naive) +Phase2Placebo+Gemcitabine+Docetaxel(Olaratumab Pretreated) arms [i.e.Phase2: Placebo+Gemcitabine+Docetaxel]

End point values	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2overall-20mg/kgOlaratumab+Gemcitabine+Docetaxel	Phase2:Olaratumab+Gemcitabine+Docetaxel	Phase2:Placebo+Gemcitabine+Docetaxel
Number of subjects analysed	18	24	87	88
Units: μg/mL
geometric mean (geometric coefficient of variation)	2.79 ( 70 )	3.49 ( 50 )	3.01 ( 122 )	2.35 ( 105 )

No statistical analyses for this end point

Secondary: Phase 1b/2: PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Gemcitabine

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End point title

Phase 1b/2: PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Gemcitabine ^[15]

End point description

Phase 1b/2: Due to short half-life of Gemcitabine, there was insufficient quantifiable data in the elimination phase to calculate AUC[0-∞] for any of the participants.

End point type

Secondary

End point timeframe

Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcomes were reported by combining phase 1b cohort 2+cohort2expand arms [i.e. Cohort2overall:20mg/kgOlaratumab+Gemcitabine+Docetaxel]; Phase2Olaratumab+Gemcitabine+Docetaxel (Olaratumab-naive) +Phase2Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) arms [i.e.Phase2: Olaratumab+Gemcitabine+Docetaxel]; Phase2Placebo+Gemcitabine+Docetaxel (Olaratumab-naive) +Phase2Placebo+Gemcitabine+Docetaxel(Olaratumab Pretreated) arms [i.e.Phase2: Placebo+Gemcitabine+Docetaxel]

End point values	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2overall-20mg/kgOlaratumab+Gemcitabine+Docetaxel	Phase2:Olaratumab+Gemcitabine+Docetaxel	Phase2:Placebo+Gemcitabine+Docetaxel
Number of subjects analysed	0 ^[16]	0 ^[17]	0 ^[18]	0 ^[19]
Units: nanograms*hours per milliliter
geometric mean (geometric coefficient of variation)	( )	( )	( )	( )

Notes
[16] - Zero participants analysed due to insufficient quantifiable data in the elimination phase.
[17] - Zero participants analysed due to insufficient quantifiable data in the elimination phase.
[18] - Zero participants analysed due to insufficient quantifiable data in the elimination phase.
[19] - Zero participants analysed due to insufficient quantifiable data in the elimination phase.

No statistical analyses for this end point

Secondary: Phase 1b/2: PK: Cmax of Docetaxel

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End point title

Phase 1b/2: PK: Cmax of Docetaxel ^[20]

End point description

Cmax of Docetaxel. Analysis Population Description: Phase 1b/2: All participants who received at least one dose of Docetaxel and had evaluable PK data.

End point type

Secondary

End point timeframe

5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcomes were reported by combining phase 1b cohort 2+cohort2expand arms [i.e. Cohort2overall:20mg/kgOlaratumab+Gemcitabine+Docetaxel]; Phase2Olaratumab+Gemcitabine+Docetaxel (Olaratumab-naive) +Phase2Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) arms [i.e.Phase2: Olaratumab+Gemcitabine+Docetaxel]; Phase2Placebo+Gemcitabine+Docetaxel (Olaratumab-naive) +Phase2Placebo+Gemcitabine+Docetaxel(Olaratumab Pretreated) arms [i.e.Phase2: Placebo+Gemcitabine+Docetaxel]

End point values	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2overall-20mg/kgOlaratumab+Gemcitabine+Docetaxel	Phase2:Olaratumab+Gemcitabine+Docetaxel	Phase2:Placebo+Gemcitabine+Docetaxel
Number of subjects analysed	18	30	71	73
Units: Nanograms per milliliter
geometric mean (geometric coefficient of variation)	903 ( 143 )	1110 ( 84 )	1030 ( 134 )	827 ( 102 )

No statistical analyses for this end point

Secondary: Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Docetaxel

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End point title

Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Docetaxel ^[21]

End point description

Analysis Population Description: Phase 1b/2: All participants who received at least one dose of Docetaxel and had evaluable PK data. For phase 2, zero participants analysed due to data not collected for AUC [0-∞] of Docetaxel.

End point type

Secondary

End point timeframe

5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcomes were reported by combining phase 1b cohort 2+cohort2expand arms [i.e. Cohort2overall:20mg/kgOlaratumab+Gemcitabine+Docetaxel]; Phase2Olaratumab+Gemcitabine+Docetaxel (Olaratumab-naive) +Phase2Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) arms [i.e.Phase2: Olaratumab+Gemcitabine+Docetaxel]; Phase2Placebo+Gemcitabine+Docetaxel (Olaratumab-naive) +Phase2Placebo+Gemcitabine+Docetaxel(Olaratumab Pretreated) arms [i.e.Phase2: Placebo+Gemcitabine+Docetaxel]

End point values	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2overall-20mg/kgOlaratumab+Gemcitabine+Docetaxel	Phase2:Olaratumab+Gemcitabine+Docetaxel	Phase2:Placebo+Gemcitabine+Docetaxel
Number of subjects analysed	7	18	0 ^[22]	0 ^[23]
Units: nanograms*hours per milliliter
geometric mean (geometric coefficient of variation)	4440 ( 103 )	2990 ( 83 )	( )	( )

Notes
[22] - Data not collected.
[23] - Data not collected.

No statistical analyses for this end point

Secondary: Phase 1b/2: Population PK: Clearance of Olaratumab

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End point title

Phase 1b/2: Population PK: Clearance of Olaratumab

End point description

Analysis Population Description: Phase 1b/2: All participants who received at least one dose of Olaratumab and had evaluable PK data. Phase 1b and phase 2 participants olaratumab PK data was planned to be pooled for the population PK analysis and compared to a validated PK model to confirm that PK parameters were similar to analyses from previous olaratumab studies.

End point type

Secondary

End point timeframe

Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8

End point values	Olaratumab + Gemcitabine + Docetaxel
Number of subjects analysed	178
Units: Liter Per Hour
arithmetic mean (confidence interval 95%)	0.0186 (0.0175 to 0.0192)

No statistical analyses for this end point

Secondary: Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab

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End point title

Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab

End point description

The Vss is the sum of central volume of distribution (V1) + peripheral volume of distribution (V2). Analysis Population Description: Phase 1b/2: All participants who received at least one dose of Olaratumab and had evaluable PK data. Phase 1b and phase 2 participants olaratumab PK data was planned to be pooled for the population PK analysis and compared to a validated PK model to confirm that PK parameters were similar to analyses from previous olaratumab studies.

End point type

Secondary

End point timeframe

Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8

End point values	Olaratumab + Gemcitabine + Docetaxel
Number of subjects analysed	178
Units: Liter
arithmetic mean (confidence interval 95%)	5.14 (4.68 to 5.54)

No statistical analyses for this end point

Secondary: Phase 2: Overall Survival (Olaratumab Pre-Treated)

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End point title

Phase 2: Overall Survival (Olaratumab Pre-Treated) ^[24]

End point description

OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact. Analysis Population Description: Phase 2: All randomized participants (including the censored participants). Number of participants censored in "Olaratumab+ Gemcitabine+Docetaxel(Olaratumab Pre-Treated)=20," "Placebo+Gemcitabine+Docetaxel(Olaratumab Pre-Treated)=15."

End point type

Secondary

End point timeframe

Baseline to Date of Death Due to Any Cause (Up To 38 Months)

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 2 Olaratumab Pre-Treated participants.

End point values	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)
Number of subjects analysed	46 ^[25]	43
Units: Months
median (confidence interval 95%)	19.84 (14.19 to 9999)	17.31 (10.81 to 20.30)

Notes
[25] - 9999 = N/A, There were not enough events to estimate the upper confidence limit.

Statistical analysis 1

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.148 ^[26]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.667

Confidence interval

level

95%

sides

2-sided

lower limit

0.385

upper limit

1.158

Notes
[26] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Secondary: Phase 2: Progression Free Survival (PFS)

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End point title

Phase 2: Progression Free Survival (PFS) ^[27]

End point description

PFS was defined as the time from randomization to the first date of radiologic disease progression (as defined by Response Evaluation Criteria In Solid Tumors, Version 1.1 [RECIST v.1.1]) or death due to any cause. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of randomization if no post-baseline radiographic assessment is available. Analysis Population Description: Phase 2: All randomized participants (including censored). Number of participants censored in Olaratumab+Gemcitabine+Docetaxel (Olaratumab-naive=20, Olaratumab pretreated=12), Placebo+Gemcitabine+Docetaxel(Olaratumab-naive=21, Olaratumab pretreated=16).

End point type

Secondary

End point timeframe

Baseline to Objective Disease Progression or Death from Any Cause (Up To 38 Months)

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 2 participants.

End point values	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)
Number of subjects analysed	81	46	86	43
Units: Months
median (confidence interval 95%)	7.62 (5.13 to 8.54)	5.45 (2.76 to 8.71)	4.37 (2.86 to 6.87)	4.17 (2.20 to 6.90)

Statistical analysis 1

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.055 ^[28]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.692

Confidence interval

level

95%

sides

2-sided

lower limit

0.476

upper limit

1.007

Notes
[28] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 2

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.482 ^[29]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.828

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

1.398

Notes
[29] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Secondary: Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR])

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End point title

Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR]) ^[30]

End point description

ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Analysis Population Description: Phase 2: All randomized participants.

End point type

Secondary

End point timeframe

Baseline to Objective Disease Progression or Start of New Anti-Cancer Therapy (Up To 38 Months)

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 2 participants.

End point values	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)
Number of subjects analysed	81	46	86	43
Units: Percentage of participants
number (confidence interval 95%)	32.1 (22.2 to 43.4)	30.4 (17.7 to 45.8)	23.3 (14.8 to 33.6)	14 (5.3 to 27.9)

Statistical analysis 1

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1891 ^[31]

Method

Exact Mantel-Haenszel test

Parameter type

Odds ratio (OR)

Point estimate

1.589

Confidence interval

level

95%

sides

2-sided

lower limit

0.794

upper limit

3.179

Notes
[31] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 2

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0642 ^[32]

Method

Exact Mantel-Haenszel test

Parameter type

Odds ratio (OR)

Point estimate

2.668

Confidence interval

level

95%

sides

2-sided

lower limit

0.923

upper limit

7.71

Notes
[32] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Secondary: Phase 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD)

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End point title

Phase 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) ^[33]

End point description

DCR is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Analysis Population Description: Phase 2: All randomized participants

End point type

Secondary

End point timeframe

Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 38 Months)

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 2 participants.

End point values	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)
Number of subjects analysed	81	46	86	43
Units: Percentage of participants
number (confidence interval 95%)	74.1 (63.1 to 83.2)	67.4 (52.0 to 80.5)	72.1 (61.4 to 81.2)	62.8 (46.7 to 77.0)

Statistical analysis 1

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7724 ^[34]

Method

Exact Mantel-Haenszel test

Parameter type

Odds ratio (OR)

Point estimate

1.106

Confidence interval

level

95%

sides

2-sided

lower limit

0.558

upper limit

2.194

Notes
[34] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 2

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6508 ^[35]

Method

Exact Mantel-Haenszel test

Parameter type

Odds ratio (OR)

Point estimate

1.222

Confidence interval

level

95%

sides

2-sided

lower limit

0.513

upper limit

2.911

Notes
[35] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Secondary: Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"

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End point title

Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score" ^[36]

End point description

The mBPI-sf is a 11-item instrument used as a multiple-item measure of cancer pain intensity ranging from 0 (no pain or does not interfere) to 10 (pain as bad as you can imagine or completely interferes). Time to first worsening of the mBPI-sf "worst pain score" (TWP) was defined as the time from the date of randomization to the first date of either a "worst pain" score increase of greater than or equal to (≥) 2 points from baseline or an analgesic drug class increase of ≥1 level. If the patient has not worsened by either of these criteria, TWP was censored for analysis on the last date the mBPI-sf was administered. Analysis Population Description: Phase 2: All randomized participants who had baseline and at least one post-baseline assessment (including the censored participants). Number of participants censored in Olaratumab+Gemcitabine+Docetaxel (Olaratumab-naive=30, Olaratumab pretreated=17), Placebo+Gemcitabine+Docetaxel(Olaratumab-naive=23, Olaratumab pretreated=8).

End point type

Secondary

End point timeframe

Baseline to Follow-up (Up To 24 Months)

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 2 participants.

End point values	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)
Number of subjects analysed	68	41	71	34
Units: Months
median (confidence interval 95%)	3.61 (2.66 to 8.57)	3.15 (1.41 to 7.62)	2.27 (1.41 to 6.54)	2.20 (0.76 to 3.02)

Statistical analysis 1

Comparison groups

Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.073 ^[37]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.661

Confidence interval

level

95%

sides

2-sided

lower limit

0.419

upper limit

1.041

Notes
[37] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 2

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.225 ^[38]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.703

Confidence interval

level

95%

sides

2-sided

lower limit

0.395

upper limit

1.253

Notes
[38] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Secondary: Phase 2: Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Symptom Scales.

Top of page

End point title

Phase 2: Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Symptom Scales. ^[39]

End point description

The EORTC QLQ-C30 is a self-reported general cancer instrument consisting of 30 items covered by 1 of 3 dimensions: global health status/quality of life(2 items), functional scales(15 items addressing either physical,role,emotional,cognitive,or social functioning), symptom scales (13 items addressing either fatigue,nausea/vomiting,pain,dyspnoea,insomnia,appetite loss,constipation,diarrhoea,or financial impact). Time to first worsening of Symptom Burden was the time from randomization to the first observation of worsening on symptom scales (i.e.,) increase of at least 10 points from baseline. For symptom scales, a linear transformation was used to obtain total score ranging from 0 to 100, a high score represents a high level of symptomatology or problems. Analysis Population Description: Phase 2: All randomized participants who had baseline and at least one post-baseline assessment. 9999=N/A, There were not enough events to estimate the median/upper confidence limit, as applicable.

End point type

Secondary

End point timeframe

Baseline to Follow-up (Up to 33 months)

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 2 participants.

End point values	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)
Number of subjects analysed	75 ^[40]	45 ^[41]	78 ^[42]	41 ^[43]
Units: Months
median (confidence interval 95%)
Fatigue	0.95 (0.76 to 1.12)	0.85 (0.72 to 1.41)	0.95 (0.76 to 1.45)	0.76 (0.72 to 1.84)
Nausea and vomiting	3.78 (2.14 to 9999)	3.98 (1.41 to 9999)	2.46 (0.99 to 13.34)	13.17 (1.64 to 9999)
Pain	4.67 (2.33 to 9.53)	2.43 (1.41 to 8.77)	0.99 (0.79 to 2.76)	3.06 (0.76 to 5.55)
Dyspnoea	2.14 (1.51 to 3.06)	2.33 (1.45 to 14.09)	2.14 (1.48 to 2.86)	2.79 (1.45 to 8.05)
Insomnia	5.32 (2.33 to 7.72)	1.91 (1.41 to 6.47)	4.24 (1.48 to 16.82)	5.09 (1.45 to 9999)
Appetite loss	1.12 (0.82 to 2.14)	1.41 (0.85 to 3.52)	2.56 (1.64 to 3.98)	1.97 (1.38 to 4.04)
Constipation	3.25 (2.14 to 5.98)	4.63 (1.91 to 12.91)	2.86 (1.48 to 9999)	3.81 (1.97 to 9999)
Diarrhoea	1.41 (0.99 to 3.68)	3.55 (1.41 to 6.05)	1.81 (1.41 to 4.24)	3.52 (1.97 to 9999)
Financial difficulties	9999 (5.32 to 9999)	7.29 (2.33 to 7.85)	7.66 (3.29 to 9999)	9999 (3.94 to 9999)

Notes
[40] - Nausea/vomiting,Dyspnoea=74, Pain,Constipation,Appetite loss=73, Insomnia=68,Financial difficulty=67
[41] - Fatigue,Nausea&vomiting,Pain,Constipation,Diarrhoea=44, Financial,Dyspnoea=43,Insomnia=41
[42] - Constipation,Fatigue,Pain=77,Insomnia=74,Appetite loss=76,Diarrhoea=80,Financial difficulty=71
[43] - Fatigue,Dyspnoea,=39,Pain,Financial difficulty=35,Insomnia=38,Appetite loss=37,Constipation=40

Statistical analysis 1

Statistical analysis description

Fatigue

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority ^[44]

P-value

= 0.332 ^[45]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.213

Confidence interval

level

95%

sides

2-sided

lower limit

0.834

upper limit

1.764

Notes
[44] - Fatigue
[45] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 2

Statistical analysis description

Nausea and vomiting

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority ^[46]

P-value

= 0.389 ^[47]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.813

Confidence interval

level

95%

sides

2-sided

lower limit

0.514

upper limit

1.287

Notes
[46] - Nausea and vomiting
[47] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 3

Statistical analysis description

Pain

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority ^[48]

P-value

= 0.02 ^[49]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.598

Confidence interval

level

95%

sides

2-sided

lower limit

0.386

upper limit

0.926

Notes
[48] - Pain
[49] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 4

Statistical analysis description

Dyspnoea

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority ^[50]

P-value

= 0.821 ^[51]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.947

Confidence interval

level

95%

sides

2-sided

lower limit

0.622

upper limit

1.442

Notes
[50] - Dyspnoea
[51] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 5

Statistical analysis description

Insomnia

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority ^[52]

P-value

= 0.812 ^[53]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.931

Confidence interval

level

95%

sides

2-sided

lower limit

0.574

upper limit

1.509

Notes
[52] - Insomnia
[53] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 6

Statistical analysis description

Appetite loss

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority ^[54]

P-value

= 0.162 ^[55]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.355

Confidence interval

level

95%

sides

2-sided

lower limit

0.893

upper limit

2.055

Notes
[54] - Appetite loss
[55] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 7

Statistical analysis description

Constipation

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority ^[56]

P-value

= 0.619 ^[57]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.881

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.413

Notes
[56] - Constipation
[57] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 8

Statistical analysis description

Diarrhoea

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority ^[58]

P-value

= 0.597 ^[59]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.134

Confidence interval

level

95%

sides

2-sided

lower limit

0.746

upper limit

1.724

Notes
[58] - Diarrhoea
[59] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 9

Statistical analysis description

Financial difficulties

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority ^[60]

P-value

= 0.38 ^[61]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.766

Confidence interval

level

95%

sides

2-sided

lower limit

0.425

upper limit

1.381

Notes
[60] - Financial difficulties
[61] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 10

Statistical analysis description

Fatigue

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[62]

P-value

= 0.877 ^[63]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.046

Confidence interval

level

95%

sides

2-sided

lower limit

0.635

upper limit

1.723

Notes
[62] - Fatigue
[63] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 11

Statistical analysis description

Nausea and vomiting

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[64]

P-value

= 0.791 ^[65]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.102

Confidence interval

level

95%

sides

2-sided

lower limit

0.568

upper limit

2.139

Notes
[64] - Nausea and vomiting
[65] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 12

Statistical analysis description

Pain

Comparison groups

Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated) v Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[66]

P-value

= 0.487 ^[67]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.454

upper limit

1.443

Notes
[66] - Pain
[67] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 13

Statistical analysis description

Dyspnoea

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[68]

P-value

= 0.976 ^[69]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.014

Confidence interval

level

95%

sides

2-sided

lower limit

0.556

upper limit

1.85

Notes
[68] - Dyspnoea
[69] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 14

Statistical analysis description

Insomnia

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[70]

P-value

= 0.111 ^[71]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.694

Confidence interval

level

95%

sides

2-sided

lower limit

0.882

upper limit

3.25

Notes
[70] - Insomnia
[71] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 15

Statistical analysis description

Appetite loss

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[72]

P-value

= 0.76 ^[73]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.108

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

1.979

Notes
[72] - Appetite loss
[73] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 16

Statistical analysis description

Constipation

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[74]

P-value

= 0.747 ^[75]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.119

Confidence interval

level

95%

sides

2-sided

lower limit

0.586

upper limit

2.135

Notes
[74] - Constipation
[75] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 17

Statistical analysis description

Diarrhoea

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[76]

P-value

= 0.33 ^[77]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.367

Confidence interval

level

95%

sides

2-sided

lower limit

0.726

upper limit

2.576

Notes
[76] - Diarrhoea
[77] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Statistical analysis 18

Statistical analysis description

Financial difficulties

Comparison groups

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated) v Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[78]

P-value

= 0.411 ^[79]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.373

Confidence interval

level

95%

sides

2-sided

lower limit

0.636

upper limit

2.965

Notes
[78] - Financial difficulties
[79] - Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).

Secondary: Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)

Top of page

End point title

Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L) ^[80]

End point description

The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of health status are each assessed with 5 response options (1=no problem, 2=slight, 3=moderate, 4=severe, and 5=extreme problem) and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status. Additionally, current health status was assessed on a visual analogue scale (VAS) ranging from 0 to 100 with a higher score representing better health status. Analysis Population Description: Phase 2: All randomized participants who completed EQ-5D-5L.

End point type

Secondary

End point timeframe

Cycle 1 (Day 1), Follow-up (Up to 38 Months)

Notes
[80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 2 participants.

End point values	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)
Number of subjects analysed	71 ^[81]	42 ^[82]	75 ^[83]	35 ^[84]
Units: score on a scale
arithmetic mean (standard deviation)
EQ-5D-5L - Index Value [Cycle 1 (Day 1)]	0.80 ( 0.17 )	0.83 ( 0.15 )	0.81 ( 0.17 )	0.83 ( 0.22 )
EQ-5D-5L - VAS Score [Cycle 1 (Day 1)]	73.5 ( 18.9 )	76.2 ( 19.6 )	72.7 ( 18.1 )	70.3 ( 23.8 )
EQ-5D-5L - Index Value [Follow-up (Up to 38 Months	0.74 ( 0.21 )	0.80 ( 0.20 )	0.71 ( 0.26 )	0.76 ( 0.24 )
EQ-5D-5L - VAS Score [Follow-up (Up to 38 Months)]	68.7 ( 16.5 )	74.8 ( 21.8 )	63.0 ( 21.6 )	70.8 ( 24.2 )

Notes
[81] - EQ-5D-5L- Index Value, VAS Score Follow-up (Up to 38 Months) = 42 Participants
[82] - EQ-5D-5L- Index Value Cycle 1 (Day 1) = 39; Index Value, VAS Score Follow-up (Up to 38 Months) = 26
[83] - EQ-5D-5L- Index Value Cycle 1 (Day 1) = 74; Index Value, VAS Score Follow-up (Up to 38 Months) = 50
[84] - EQ-5D-5L- Index Value, VAS Score Follow-up (Up to 38 Months) = 25

No statistical analyses for this end point

Secondary: Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies

Top of page

End point title

Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies ^[85]

End point description

Phase 2: Analysis Population Description: All randomized participants who received at least one dose of Olaratumab and had evaluable immunogenicity data.

End point type

Secondary

End point timeframe

Baseline through Follow-Up (Up to 38 Months)

Notes
[85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Outcome reporting is only for Phase 2 participants.

End point values	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)
Number of subjects analysed	77	43
Units: Participants	0	0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline to Follow-up (Up To 38 Months)

Adverse event reporting additional description

Phase 1b/2: All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel

Reporting group description

Reporting group title

Phase1b:Cohort2Expand:20mg/kgOlaratumab+Gemcitabine+Docetaxe

Reporting group description

Reporting group title

Phase1b:Cohort2: 20mg/kg Olaratumab+Gemcitabine+Docetaxel

Reporting group description

Reporting group title

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)

Reporting group description

Reporting group title

Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)

Reporting group description

Reporting group title

Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)

Reporting group description

Reporting group title

Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)

Reporting group description

Serious adverse events	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2Expand:20mg/kgOlaratumab+Gemcitabine+Docetaxe	Phase1b:Cohort2: 20mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 21 (28.57%)	9 / 15 (60.00%)	9 / 18 (50.00%)	44 / 81 (54.32%)	21 / 45 (46.67%)	38 / 86 (44.19%)	23 / 43 (53.49%)
number of deaths (all causes)	15	12	11	54	28	58	28
number of deaths resulting from adverse events	0	0	0	0	1	0	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
tumour haemorrhage
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
capillary leak syndrome
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deep vein thrombosis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	2 / 45 (4.44%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 3	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
embolism
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
haematoma
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
haemorrhage
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
hypotension
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
peripheral artery stenosis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
chest pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
fatigue
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	3 / 81 (3.70%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	3 / 3	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
influenza like illness
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
mucosal inflammation
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
non-cardiac chest pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
oedema
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
oedema peripheral
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	2 / 81 (2.47%)	2 / 45 (4.44%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
peripheral swelling
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pyrexia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	7 / 81 (8.64%)	2 / 45 (4.44%)	7 / 86 (8.14%)	6 / 43 (13.95%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	7 / 10	1 / 2	4 / 8	2 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
sudden death
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
anaphylactic reaction
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
anaphylactic shock
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
cough
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
dyspnoea
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	3 / 81 (3.70%)	2 / 45 (4.44%)	4 / 86 (4.65%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	2 / 4	1 / 2	2 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
epistaxis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	2 / 86 (2.33%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
hypoxia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
interstitial lung disease
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumonitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	1 / 81 (1.23%)	1 / 45 (2.22%)	2 / 86 (2.33%)	4 / 43 (9.30%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1	1 / 1	2 / 2	4 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumothorax
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pulmonary embolism
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pulmonary haemorrhage
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pulmonary oedema
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
respiratory failure
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	2 / 43 (4.65%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
Psychiatric disorders
confusional state
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
alanine aminotransferase increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
international normalised ratio increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
neutrophil count decreased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
platelet count decreased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	2 / 81 (2.47%)	1 / 45 (2.22%)	2 / 86 (2.33%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	2 / 2	2 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
troponin increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
white blood cell count decreased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
arterial bypass occlusion
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
fall
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
femoral neck fracture
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
femur fracture
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
hip fracture
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
infusion related reaction
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
skull fracture
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Cardiac disorders
atrial fibrillation
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
atrial tachycardia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
cardiac failure
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
myocardial infarction
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
pericardial effusion
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
supraventricular tachycardia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
dizziness
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
epilepsy
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
facial paralysis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
headache
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
nervous system disorder
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
polyneuropathy
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
seizure
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
spinal cord compression
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
syncope
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	4 / 81 (4.94%)	2 / 45 (4.44%)	4 / 86 (4.65%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	4 / 7	2 / 2	4 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
bandaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
febrile neutropenia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	1 / 18 (5.56%)	6 / 81 (7.41%)	1 / 45 (2.22%)	3 / 86 (3.49%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	6 / 6	1 / 1	3 / 3	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
haemolytic uraemic syndrome
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
hypochromic anaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
neutropenia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	2 / 45 (4.44%)	2 / 86 (2.33%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1	2 / 2	2 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
neutrophilia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
normocytic anaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pancytopenia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	2 / 86 (2.33%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
thrombocytopenia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	2 / 81 (2.47%)	3 / 45 (6.67%)	3 / 86 (3.49%)	2 / 43 (4.65%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	3 / 3	5 / 5	5 / 5	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
thrombotic microangiopathy
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
hypoacusis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
abdominal pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	1 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
constipation
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
diarrhoea
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	2 / 81 (2.47%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
enterocolitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
gastritis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
haemorrhoidal haemorrhage
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
nausea
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	2 / 81 (2.47%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
oesophageal ulcer
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
rectal haemorrhage
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
small intestinal obstruction
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
stomatitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	3 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
vomiting
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	2 / 81 (2.47%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
hepatic failure
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
jaundice cholestatic
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
eczema
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
petechiae
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
acute kidney injury
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	2 / 86 (2.33%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
renal failure
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	2 / 81 (2.47%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
urinary retention
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
arthritis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
back pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
muscular weakness
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
myalgia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
myositis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
anorectal infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
appendicitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
arthritis infective
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
bacteraemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
bronchitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
campylobacter infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
cellulitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	1 / 15 (6.67%)	1 / 18 (5.56%)	2 / 81 (2.47%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	2 / 4	0 / 1	0 / 1	1 / 2	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
clostridium difficile colitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
cystitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	2 / 86 (2.33%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
device related infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
diverticulitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	2 / 81 (2.47%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
erysipelas
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
gastrointestinal infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
influenza
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
lower respiratory tract infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	2 / 81 (2.47%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
neutropenic sepsis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumonia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	0 / 15 (0.00%)	0 / 18 (0.00%)	5 / 81 (6.17%)	3 / 45 (6.67%)	6 / 86 (6.98%)	5 / 43 (11.63%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	4 / 5	2 / 3	2 / 6	3 / 5
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumonia bacterial
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
pneumonia viral
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
rectal abscess
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
respiratory tract infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
sepsis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	2 / 81 (2.47%)	0 / 45 (0.00%)	1 / 86 (1.16%)	2 / 43 (4.65%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 2	0 / 0	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
septic shock
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
skin infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
staphylococcal bacteraemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
urinary tract infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	4 / 81 (4.94%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	3 / 4	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
viral infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
dehydration
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	2 / 81 (2.47%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
hypokalaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Phase1b:Cohort1: 15mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase1b:Cohort2Expand:20mg/kgOlaratumab+Gemcitabine+Docetaxe	Phase1b:Cohort2: 20mg/kg Olaratumab+Gemcitabine+Docetaxel	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Olaratumab+Gemcitabine+Docetaxel(Olaratumab Pretreated)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab-naive)	Phase2:Placebo+Gemcitabine+Docetaxel(Olaratumab pretreated)
Total subjects affected by non serious adverse events
subjects affected / exposed	21 / 21 (100.00%)	15 / 15 (100.00%)	18 / 18 (100.00%)	78 / 81 (96.30%)	45 / 45 (100.00%)	81 / 86 (94.19%)	42 / 43 (97.67%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
tumour pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	1 / 45 (2.22%)	2 / 86 (2.33%)	0 / 43 (0.00%)
occurrences all number	4	0	0	1	1	4	0
Vascular disorders
embolism
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	1 / 81 (1.23%)	2 / 45 (4.44%)	6 / 86 (6.98%)	2 / 43 (4.65%)
occurrences all number	0	1	0	1	2	6	2
embolism venous
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0	0	0	0
flushing
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	2 / 18 (11.11%)	10 / 81 (12.35%)	2 / 45 (4.44%)	4 / 86 (4.65%)	5 / 43 (11.63%)
occurrences all number	0	0	2	13	2	7	6
hot flush
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	0 / 18 (0.00%)	4 / 81 (4.94%)	1 / 45 (2.22%)	5 / 86 (5.81%)	3 / 43 (6.98%)
occurrences all number	1	0	0	5	1	9	3
hypertension
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	2 / 15 (13.33%)	0 / 18 (0.00%)	5 / 81 (6.17%)	6 / 45 (13.33%)	7 / 86 (8.14%)	6 / 43 (13.95%)
occurrences all number	3	2	0	20	6	23	7
hypotension
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	2 / 15 (13.33%)	0 / 18 (0.00%)	4 / 81 (4.94%)	8 / 45 (17.78%)	5 / 86 (5.81%)	2 / 43 (4.65%)
occurrences all number	2	2	0	4	8	5	2
peripheral venous disease
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	0	0
phlebitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	0	1	1	0	1	0
Surgical and medical procedures
orchidectomy
alternative dictionary used: MedDRA 21.0
subjects affected / exposed ^[1]	0 / 10 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 33 (0.00%)	0 / 17 (0.00%)	0 / 28 (0.00%)	0 / 15 (0.00%)
occurrences all number	0	1	0	0	0	0	0
General disorders and administration site conditions
asthenia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	4 / 21 (19.05%)	0 / 15 (0.00%)	2 / 18 (11.11%)	12 / 81 (14.81%)	1 / 45 (2.22%)	14 / 86 (16.28%)	3 / 43 (6.98%)
occurrences all number	21	0	8	59	1	58	9
catheter site pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	1	0	0	0
chills
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	1 / 15 (6.67%)	2 / 18 (11.11%)	8 / 81 (9.88%)	5 / 45 (11.11%)	4 / 86 (4.65%)	7 / 43 (16.28%)
occurrences all number	1	1	3	13	5	5	8
device related thrombosis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	1	0	0	0
face oedema
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	5 / 81 (6.17%)	2 / 45 (4.44%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	8	2	0	1
fatigue
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	13 / 21 (61.90%)	12 / 15 (80.00%)	14 / 18 (77.78%)	49 / 81 (60.49%)	34 / 45 (75.56%)	45 / 86 (52.33%)	23 / 43 (53.49%)
occurrences all number	32	21	35	126	76	110	44
influenza like illness
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	2 / 18 (11.11%)	5 / 81 (6.17%)	3 / 45 (6.67%)	3 / 86 (3.49%)	1 / 43 (2.33%)
occurrences all number	1	0	2	5	3	6	1
infusion site extravasation
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	2 / 81 (2.47%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	2	0	0	0
localised oedema
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	3 / 45 (6.67%)	0 / 86 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	0	1	1	3	0	2
malaise
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	1 / 18 (5.56%)	2 / 81 (2.47%)	1 / 45 (2.22%)	2 / 86 (2.33%)	1 / 43 (2.33%)
occurrences all number	1	0	1	3	1	2	1
non-cardiac chest pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	1 / 15 (6.67%)	1 / 18 (5.56%)	7 / 81 (8.64%)	3 / 45 (6.67%)	8 / 86 (9.30%)	3 / 43 (6.98%)
occurrences all number	2	1	1	9	4	8	3
non-pitting oedema
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	0	0
oedema peripheral
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	8 / 21 (38.10%)	5 / 15 (33.33%)	5 / 18 (27.78%)	37 / 81 (45.68%)	21 / 45 (46.67%)	23 / 86 (26.74%)	14 / 43 (32.56%)
occurrences all number	13	8	9	67	36	33	21
pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	2 / 18 (11.11%)	3 / 81 (3.70%)	1 / 45 (2.22%)	1 / 86 (1.16%)	1 / 43 (2.33%)
occurrences all number	1	0	2	3	1	1	1
peripheral swelling
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	6 / 81 (7.41%)	1 / 45 (2.22%)	8 / 86 (9.30%)	0 / 43 (0.00%)
occurrences all number	0	1	0	6	2	11	0
pyrexia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	6 / 21 (28.57%)	2 / 15 (13.33%)	8 / 18 (44.44%)	23 / 81 (28.40%)	10 / 45 (22.22%)	26 / 86 (30.23%)	11 / 43 (25.58%)
occurrences all number	8	2	11	51	12	49	17
Respiratory, thoracic and mediastinal disorders
cough
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	1 / 15 (6.67%)	6 / 18 (33.33%)	16 / 81 (19.75%)	13 / 45 (28.89%)	21 / 86 (24.42%)	9 / 43 (20.93%)
occurrences all number	3	3	9	22	21	27	10
dyspnoea
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	5 / 15 (33.33%)	7 / 18 (38.89%)	19 / 81 (23.46%)	15 / 45 (33.33%)	18 / 86 (20.93%)	12 / 43 (27.91%)
occurrences all number	4	9	11	30	30	25	19
dyspnoea exertional
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	0 / 81 (0.00%)	2 / 45 (4.44%)	5 / 86 (5.81%)	1 / 43 (2.33%)
occurrences all number	0	0	0	0	4	7	1
epistaxis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	4 / 21 (19.05%)	2 / 15 (13.33%)	1 / 18 (5.56%)	16 / 81 (19.75%)	5 / 45 (11.11%)	17 / 86 (19.77%)	9 / 43 (20.93%)
occurrences all number	4	5	1	19	6	22	11
haemoptysis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	1	0	1	0	2	0
hiccups
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	3 / 18 (16.67%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	1 / 43 (2.33%)
occurrences all number	0	1	3	0	0	1	1
hypoxia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	2 / 15 (13.33%)	0 / 18 (0.00%)	3 / 81 (3.70%)	2 / 45 (4.44%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	2	0	3	2	0	3
laryngeal haemorrhage
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	0	0
lower respiratory tract congestion
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	0	0
nasal congestion
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	1 / 15 (6.67%)	2 / 18 (11.11%)	2 / 81 (2.47%)	1 / 45 (2.22%)	0 / 86 (0.00%)	2 / 43 (4.65%)
occurrences all number	3	2	3	2	1	0	2
nasal dryness
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	0	0
oropharyngeal pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	9 / 81 (11.11%)	4 / 45 (8.89%)	6 / 86 (6.98%)	0 / 43 (0.00%)
occurrences all number	0	0	0	11	4	6	0
pleural effusion
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	2 / 18 (11.11%)	2 / 81 (2.47%)	6 / 45 (13.33%)	1 / 86 (1.16%)	4 / 43 (9.30%)
occurrences all number	0	1	2	4	7	1	4
pneumonitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	7 / 81 (8.64%)	3 / 45 (6.67%)	1 / 86 (1.16%)	3 / 43 (6.98%)
occurrences all number	0	1	0	8	3	1	3
productive cough
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	0 / 18 (0.00%)	3 / 81 (3.70%)	4 / 45 (8.89%)	5 / 86 (5.81%)	3 / 43 (6.98%)
occurrences all number	2	0	0	3	6	6	4
pulmonary embolism
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	2 / 15 (13.33%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	1 / 86 (1.16%)	1 / 43 (2.33%)
occurrences all number	0	2	0	0	1	1	1
upper-airway cough syndrome
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	2 / 81 (2.47%)	3 / 45 (6.67%)	2 / 86 (2.33%)	1 / 43 (2.33%)
occurrences all number	0	0	1	3	3	2	1
Psychiatric disorders
anxiety
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	2 / 15 (13.33%)	3 / 18 (16.67%)	5 / 81 (6.17%)	2 / 45 (4.44%)	5 / 86 (5.81%)	3 / 43 (6.98%)
occurrences all number	0	2	5	5	2	5	4
depression
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	2 / 18 (11.11%)	1 / 81 (1.23%)	0 / 45 (0.00%)	2 / 86 (2.33%)	2 / 43 (4.65%)
occurrences all number	0	0	2	2	0	2	2
insomnia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	1 / 18 (5.56%)	15 / 81 (18.52%)	6 / 45 (13.33%)	7 / 86 (8.14%)	10 / 43 (23.26%)
occurrences all number	0	1	1	17	7	8	11
nightmare
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Investigations
alanine aminotransferase increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	5 / 21 (23.81%)	2 / 15 (13.33%)	6 / 18 (33.33%)	13 / 81 (16.05%)	8 / 45 (17.78%)	16 / 86 (18.60%)	7 / 43 (16.28%)
occurrences all number	7	2	13	36	19	33	20
aspartate aminotransferase increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	4 / 21 (19.05%)	2 / 15 (13.33%)	4 / 18 (22.22%)	10 / 81 (12.35%)	6 / 45 (13.33%)	11 / 86 (12.79%)	3 / 43 (6.98%)
occurrences all number	4	2	7	22	15	14	7
blood alkaline phosphatase increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	4 / 21 (19.05%)	2 / 15 (13.33%)	3 / 18 (16.67%)	7 / 81 (8.64%)	11 / 45 (24.44%)	4 / 86 (4.65%)	3 / 43 (6.98%)
occurrences all number	4	2	6	15	22	6	6
blood bilirubin increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	3 / 18 (16.67%)	2 / 81 (2.47%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	4	2	1	0	0
blood creatinine increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	2 / 18 (11.11%)	2 / 81 (2.47%)	3 / 45 (6.67%)	4 / 86 (4.65%)	2 / 43 (4.65%)
occurrences all number	0	0	2	6	3	4	9
blood thyroid stimulating hormone increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	2	0	0	0
gamma-glutamyltransferase increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	4 / 21 (19.05%)	0 / 15 (0.00%)	3 / 18 (16.67%)	4 / 81 (4.94%)	4 / 45 (8.89%)	1 / 86 (1.16%)	3 / 43 (6.98%)
occurrences all number	5	0	5	5	4	4	5
haemoglobin decreased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	2	0	0	0
international normalised ratio increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	2 / 15 (13.33%)	3 / 18 (16.67%)	0 / 81 (0.00%)	2 / 45 (4.44%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	2	3	0	2	0	0
lymphocyte count decreased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	4 / 18 (22.22%)	8 / 81 (9.88%)	5 / 45 (11.11%)	9 / 86 (10.47%)	3 / 43 (6.98%)
occurrences all number	3	0	15	31	32	33	4
neutrophil count decreased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	5 / 18 (27.78%)	16 / 81 (19.75%)	20 / 45 (44.44%)	14 / 86 (16.28%)	4 / 43 (9.30%)
occurrences all number	3	0	7	44	72	32	4
platelet count decreased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	2 / 15 (13.33%)	7 / 18 (38.89%)	19 / 81 (23.46%)	15 / 45 (33.33%)	16 / 86 (18.60%)	7 / 43 (16.28%)
occurrences all number	2	2	15	50	44	46	10
transaminases increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	3	0	0	0	1	0
weight decreased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	4 / 18 (22.22%)	5 / 81 (6.17%)	3 / 45 (6.67%)	6 / 86 (6.98%)	5 / 43 (11.63%)
occurrences all number	0	0	6	9	4	14	7
weight increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	7 / 81 (8.64%)	0 / 45 (0.00%)	1 / 86 (1.16%)	1 / 43 (2.33%)
occurrences all number	0	0	1	11	0	1	2
white blood cell count decreased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	0 / 15 (0.00%)	4 / 18 (22.22%)	12 / 81 (14.81%)	12 / 45 (26.67%)	12 / 86 (13.95%)	4 / 43 (9.30%)
occurrences all number	3	0	11	50	63	43	6
Injury, poisoning and procedural complications
fall
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	1 / 81 (1.23%)	2 / 45 (4.44%)	2 / 86 (2.33%)	2 / 43 (4.65%)
occurrences all number	0	1	0	1	4	3	2
infusion related reaction
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	2 / 15 (13.33%)	0 / 18 (0.00%)	2 / 81 (2.47%)	0 / 45 (0.00%)	2 / 86 (2.33%)	0 / 43 (0.00%)
occurrences all number	3	2	0	2	0	2	0
meniscus injury
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0	0	0	0
wound complication
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Cardiac disorders
atrial fibrillation
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0	0	1	0
sinus tachycardia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	3 / 81 (3.70%)	3 / 45 (6.67%)	5 / 86 (5.81%)	2 / 43 (4.65%)
occurrences all number	0	1	0	5	3	8	4
tachycardia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	3 / 81 (3.70%)	2 / 45 (4.44%)	3 / 86 (3.49%)	1 / 43 (2.33%)
occurrences all number	0	1	0	3	2	3	2
Nervous system disorders
dizziness
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	2 / 15 (13.33%)	2 / 18 (11.11%)	11 / 81 (13.58%)	3 / 45 (6.67%)	9 / 86 (10.47%)	4 / 43 (9.30%)
occurrences all number	0	4	2	26	4	12	4
dysgeusia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	0 / 15 (0.00%)	7 / 18 (38.89%)	12 / 81 (14.81%)	13 / 45 (28.89%)	11 / 86 (12.79%)	14 / 43 (32.56%)
occurrences all number	7	0	7	20	21	11	18
headache
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	5 / 21 (23.81%)	1 / 15 (6.67%)	5 / 18 (27.78%)	15 / 81 (18.52%)	6 / 45 (13.33%)	13 / 86 (15.12%)	5 / 43 (11.63%)
occurrences all number	6	1	5	23	7	15	5
memory impairment
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	2	1	1	0	0
neuropathy peripheral
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	1 / 15 (6.67%)	1 / 18 (5.56%)	7 / 81 (8.64%)	0 / 45 (0.00%)	5 / 86 (5.81%)	1 / 43 (2.33%)
occurrences all number	1	1	1	10	0	5	1
paraesthesia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	1 / 15 (6.67%)	0 / 18 (0.00%)	3 / 81 (3.70%)	4 / 45 (8.89%)	4 / 86 (4.65%)	3 / 43 (6.98%)
occurrences all number	2	1	0	4	5	4	3
peripheral motor neuropathy
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	3 / 81 (3.70%)	1 / 45 (2.22%)	3 / 86 (3.49%)	0 / 43 (0.00%)
occurrences all number	0	0	2	6	2	8	0
peripheral sensory neuropathy
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	3 / 18 (16.67%)	10 / 81 (12.35%)	10 / 45 (22.22%)	13 / 86 (15.12%)	9 / 43 (20.93%)
occurrences all number	0	1	4	15	20	31	14
sciatica
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0	1	1	0
syncope
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	3 / 81 (3.70%)	2 / 45 (4.44%)	2 / 86 (2.33%)	3 / 43 (6.98%)
occurrences all number	0	0	0	4	2	6	3
taste disorder
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	4 / 81 (4.94%)	0 / 45 (0.00%)	1 / 86 (1.16%)	3 / 43 (6.98%)
occurrences all number	0	0	0	5	0	1	3
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	13 / 21 (61.90%)	9 / 15 (60.00%)	12 / 18 (66.67%)	43 / 81 (53.09%)	33 / 45 (73.33%)	47 / 86 (54.65%)	20 / 43 (46.51%)
occurrences all number	42	24	54	168	145	147	57
leukopenia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	7 / 81 (8.64%)	1 / 45 (2.22%)	3 / 86 (3.49%)	1 / 43 (2.33%)
occurrences all number	0	0	0	13	4	6	4
neutropenia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	2 / 15 (13.33%)	3 / 18 (16.67%)	20 / 81 (24.69%)	6 / 45 (13.33%)	24 / 86 (27.91%)	4 / 43 (9.30%)
occurrences all number	4	5	4	55	6	43	10
neutrophilia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0	0	0	0
thrombocytopenia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	4 / 15 (26.67%)	3 / 18 (16.67%)	10 / 81 (12.35%)	9 / 45 (20.00%)	13 / 86 (15.12%)	6 / 43 (13.95%)
occurrences all number	8	12	3	21	18	21	12
Ear and labyrinth disorders
ear pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	1 / 18 (5.56%)	1 / 81 (1.23%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	1	1	2	0	0
Eye disorders
dry eye
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	1 / 15 (6.67%)	0 / 18 (0.00%)	2 / 81 (2.47%)	2 / 45 (4.44%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	2	1	0	2	2	0	0
lacrimation increased
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	0 / 18 (0.00%)	4 / 81 (4.94%)	3 / 45 (6.67%)	3 / 86 (3.49%)	3 / 43 (6.98%)
occurrences all number	1	0	0	4	3	3	3
photopsia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	0	0
vision blurred
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	4 / 81 (4.94%)	3 / 45 (6.67%)	2 / 86 (2.33%)	1 / 43 (2.33%)
occurrences all number	0	1	0	5	3	2	1
Gastrointestinal disorders
abdominal distension
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	3 / 81 (3.70%)	5 / 45 (11.11%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	0	0	3	5	1	0
abdominal pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	0 / 15 (0.00%)	0 / 18 (0.00%)	9 / 81 (11.11%)	7 / 45 (15.56%)	10 / 86 (11.63%)	6 / 43 (13.95%)
occurrences all number	4	0	0	11	12	10	7
abdominal pain upper
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	0 / 15 (0.00%)	0 / 18 (0.00%)	3 / 81 (3.70%)	0 / 45 (0.00%)	2 / 86 (2.33%)	2 / 43 (4.65%)
occurrences all number	3	0	0	5	0	2	2
anorectal discomfort
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	1	0	0
aphthous ulcer
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	0	0
constipation
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	6 / 21 (28.57%)	4 / 15 (26.67%)	3 / 18 (16.67%)	21 / 81 (25.93%)	12 / 45 (26.67%)	20 / 86 (23.26%)	12 / 43 (27.91%)
occurrences all number	8	6	7	29	14	24	13
diarrhoea
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	7 / 21 (33.33%)	5 / 15 (33.33%)	8 / 18 (44.44%)	36 / 81 (44.44%)	21 / 45 (46.67%)	30 / 86 (34.88%)	14 / 43 (32.56%)
occurrences all number	22	8	14	84	42	50	21
dry mouth
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	5 / 81 (6.17%)	6 / 45 (13.33%)	3 / 86 (3.49%)	4 / 43 (9.30%)
occurrences all number	0	0	0	5	6	3	4
dyspepsia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	3 / 18 (16.67%)	6 / 81 (7.41%)	2 / 45 (4.44%)	8 / 86 (9.30%)	3 / 43 (6.98%)
occurrences all number	0	2	3	9	2	9	3
gastrooesophageal reflux disease
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	6 / 45 (13.33%)	5 / 86 (5.81%)	1 / 43 (2.33%)
occurrences all number	2	2	0	0	7	5	1
haemorrhoids
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	3 / 45 (6.67%)	4 / 86 (4.65%)	1 / 43 (2.33%)
occurrences all number	1	0	0	1	3	4	1
intestinal fistula
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0	0	0	0
nausea
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	5 / 21 (23.81%)	3 / 15 (20.00%)	9 / 18 (50.00%)	38 / 81 (46.91%)	20 / 45 (44.44%)	40 / 86 (46.51%)	12 / 43 (27.91%)
occurrences all number	8	4	15	59	31	73	22
oral pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	2 / 18 (11.11%)	1 / 81 (1.23%)	1 / 45 (2.22%)	3 / 86 (3.49%)	4 / 43 (9.30%)
occurrences all number	0	0	3	1	1	3	4
proctalgia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	1 / 45 (2.22%)	2 / 86 (2.33%)	1 / 43 (2.33%)
occurrences all number	0	0	1	0	1	2	1
salivary hypersecretion
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	0	0
stomatitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	4 / 21 (19.05%)	0 / 15 (0.00%)	1 / 18 (5.56%)	17 / 81 (20.99%)	7 / 45 (15.56%)	15 / 86 (17.44%)	11 / 43 (25.58%)
occurrences all number	8	0	1	34	18	26	20
toothache
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	1 / 15 (6.67%)	0 / 18 (0.00%)	2 / 81 (2.47%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	1	0	2	0	0	0
vomiting
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	1 / 15 (6.67%)	2 / 18 (11.11%)	25 / 81 (30.86%)	7 / 45 (15.56%)	13 / 86 (15.12%)	7 / 43 (16.28%)
occurrences all number	5	1	2	30	8	17	13
Skin and subcutaneous tissue disorders
alopecia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	8 / 21 (38.10%)	1 / 15 (6.67%)	5 / 18 (27.78%)	29 / 81 (35.80%)	5 / 45 (11.11%)	32 / 86 (37.21%)	5 / 43 (11.63%)
occurrences all number	8	1	10	35	5	44	5
dermatitis acneiform
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	1 / 18 (5.56%)	3 / 81 (3.70%)	4 / 45 (8.89%)	2 / 86 (2.33%)	2 / 43 (4.65%)
occurrences all number	1	0	1	4	5	3	5
dry skin
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	2 / 18 (11.11%)	3 / 81 (3.70%)	5 / 45 (11.11%)	5 / 86 (5.81%)	5 / 43 (11.63%)
occurrences all number	0	0	2	4	5	6	5
eczema
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	1	0	1	0	2	0
erythema
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	5 / 81 (6.17%)	0 / 45 (0.00%)	5 / 86 (5.81%)	1 / 43 (2.33%)
occurrences all number	0	0	0	5	0	6	1
nail discolouration
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	5 / 81 (6.17%)	3 / 45 (6.67%)	4 / 86 (4.65%)	2 / 43 (4.65%)
occurrences all number	0	0	1	5	3	4	3
nail dystrophy
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	2 / 86 (2.33%)	0 / 43 (0.00%)
occurrences all number	3	0	1	0	0	5	0
onychomadesis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	1 / 81 (1.23%)	7 / 45 (15.56%)	3 / 86 (3.49%)	2 / 43 (4.65%)
occurrences all number	0	0	0	1	8	3	4
palmar-plantar erythrodysaesthesia syndrome
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	6 / 81 (7.41%)	3 / 45 (6.67%)	4 / 86 (4.65%)	2 / 43 (4.65%)
occurrences all number	0	0	2	16	8	7	5
pruritus
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	8 / 81 (9.88%)	2 / 45 (4.44%)	6 / 86 (6.98%)	3 / 43 (6.98%)
occurrences all number	0	0	1	8	3	8	3
rash
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	15 / 81 (18.52%)	1 / 45 (2.22%)	11 / 86 (12.79%)	2 / 43 (4.65%)
occurrences all number	0	1	0	17	1	17	3
rash maculo-papular
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	2 / 15 (13.33%)	2 / 18 (11.11%)	10 / 81 (12.35%)	6 / 45 (13.33%)	6 / 86 (6.98%)	3 / 43 (6.98%)
occurrences all number	1	2	2	17	7	7	3
rash pruritic
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	1	1	0	0
skin hyperpigmentation
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	3 / 81 (3.70%)	3 / 45 (6.67%)	4 / 86 (4.65%)	0 / 43 (0.00%)
occurrences all number	0	0	0	6	3	4	0
Renal and urinary disorders
chromaturia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	0	0
haematuria
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	5 / 81 (6.17%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	0	0	6	0	3	0
micturition urgency
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0	0	0	0
proteinuria
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	0 / 15 (0.00%)	0 / 18 (0.00%)	3 / 81 (3.70%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences all number	2	0	0	3	0	0	2
Endocrine disorders
adrenal insufficiency
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0	0	0	0
hypothyroidism
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	2 / 18 (11.11%)	3 / 81 (3.70%)	3 / 45 (6.67%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	2	5	3	0	0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	2 / 15 (13.33%)	3 / 18 (16.67%)	13 / 81 (16.05%)	6 / 45 (13.33%)	14 / 86 (16.28%)	5 / 43 (11.63%)
occurrences all number	3	3	4	24	8	18	8
back pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	4 / 21 (19.05%)	6 / 15 (40.00%)	5 / 18 (27.78%)	10 / 81 (12.35%)	7 / 45 (15.56%)	7 / 86 (8.14%)	3 / 43 (6.98%)
occurrences all number	6	7	7	16	8	10	4
bone pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	3 / 21 (14.29%)	0 / 15 (0.00%)	3 / 18 (16.67%)	9 / 81 (11.11%)	5 / 45 (11.11%)	7 / 86 (8.14%)	6 / 43 (13.95%)
occurrences all number	3	0	3	10	5	7	6
coccydynia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	1	0	0	0
muscle spasms
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	0 / 18 (0.00%)	6 / 81 (7.41%)	3 / 45 (6.67%)	1 / 86 (1.16%)	1 / 43 (2.33%)
occurrences all number	0	0	0	8	4	1	1
muscular weakness
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	2 / 18 (11.11%)	6 / 81 (7.41%)	7 / 45 (15.56%)	5 / 86 (5.81%)	5 / 43 (11.63%)
occurrences all number	0	1	2	9	8	10	5
musculoskeletal chest pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	2 / 18 (11.11%)	2 / 81 (2.47%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	5	2	0	0	1
musculoskeletal pain
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	1 / 15 (6.67%)	1 / 18 (5.56%)	1 / 81 (1.23%)	2 / 45 (4.44%)	3 / 86 (3.49%)	2 / 43 (4.65%)
occurrences all number	2	1	1	1	2	6	3
myalgia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	7 / 21 (33.33%)	4 / 15 (26.67%)	6 / 18 (33.33%)	16 / 81 (19.75%)	13 / 45 (28.89%)	11 / 86 (12.79%)	11 / 43 (25.58%)
occurrences all number	9	4	6	27	16	18	19
pain in extremity
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	2 / 18 (11.11%)	13 / 81 (16.05%)	5 / 45 (11.11%)	8 / 86 (9.30%)	4 / 43 (9.30%)
occurrences all number	0	1	4	16	7	9	4
Infections and infestations
bronchitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	2 / 81 (2.47%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	0	1	3	2	1	0
cellulitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	2 / 15 (13.33%)	0 / 18 (0.00%)	4 / 81 (4.94%)	2 / 45 (4.44%)	2 / 86 (2.33%)	1 / 43 (2.33%)
occurrences all number	0	2	0	5	2	2	1
cystitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	2 / 86 (2.33%)	1 / 43 (2.33%)
occurrences all number	0	0	1	0	0	2	1
folliculitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	1 / 81 (1.23%)	0 / 45 (0.00%)	0 / 86 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	1	0	1	0	0	1
oral candidiasis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	3 / 45 (6.67%)	3 / 86 (3.49%)	3 / 43 (6.98%)
occurrences all number	0	0	1	1	5	4	4
oral herpes
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	3 / 81 (3.70%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	3	0	0	0
paronychia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	2 / 81 (2.47%)	1 / 45 (2.22%)	1 / 86 (1.16%)	1 / 43 (2.33%)
occurrences all number	0	0	1	2	1	1	2
pneumonia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	0 / 18 (0.00%)	5 / 81 (6.17%)	5 / 45 (11.11%)	2 / 86 (2.33%)	3 / 43 (6.98%)
occurrences all number	1	0	0	5	6	2	4
rash pustular
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	2 / 81 (2.47%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	1	0	4	0	1	0
respiratory tract infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	1 / 45 (2.22%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	0	1	1	1	1	0
sinusitis
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	5 / 81 (6.17%)	2 / 45 (4.44%)	1 / 86 (1.16%)	1 / 43 (2.33%)
occurrences all number	0	1	0	5	2	1	1
skin infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	3 / 81 (3.70%)	4 / 45 (8.89%)	1 / 86 (1.16%)	1 / 43 (2.33%)
occurrences all number	0	1	0	4	4	1	3
upper respiratory tract infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	3 / 15 (20.00%)	2 / 18 (11.11%)	7 / 81 (8.64%)	3 / 45 (6.67%)	14 / 86 (16.28%)	3 / 43 (6.98%)
occurrences all number	2	3	2	9	4	19	4
urinary tract infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	2 / 18 (11.11%)	15 / 81 (18.52%)	3 / 45 (6.67%)	8 / 86 (9.30%)	1 / 43 (2.33%)
occurrences all number	1	0	2	18	4	8	1
vaginal infection
alternative dictionary used: MedDRA 21.0
subjects affected / exposed ^[2]	0 / 11 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 48 (0.00%)	0 / 28 (0.00%)	0 / 58 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	5 / 21 (23.81%)	0 / 15 (0.00%)	6 / 18 (33.33%)	21 / 81 (25.93%)	11 / 45 (24.44%)	15 / 86 (17.44%)	14 / 43 (32.56%)
occurrences all number	6	0	8	33	14	30	14
dehydration
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	1 / 15 (6.67%)	0 / 18 (0.00%)	4 / 81 (4.94%)	3 / 45 (6.67%)	2 / 86 (2.33%)	3 / 43 (6.98%)
occurrences all number	1	1	0	4	4	2	3
failure to thrive
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	1 / 15 (6.67%)	0 / 18 (0.00%)	0 / 81 (0.00%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0	0	0	0
hypercalcaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	1 / 45 (2.22%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	2	0	1	0	2	0	0
hyperglycaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	4 / 21 (19.05%)	0 / 15 (0.00%)	4 / 18 (22.22%)	6 / 81 (7.41%)	10 / 45 (22.22%)	4 / 86 (4.65%)	2 / 43 (4.65%)
occurrences all number	4	0	5	7	16	4	4
hyperkalaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	1 / 18 (5.56%)	2 / 81 (2.47%)	0 / 45 (0.00%)	0 / 86 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	2	4	0	0	0
hypernatraemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	0 / 45 (0.00%)	1 / 86 (1.16%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0	1	0
hyperuricaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	0 / 15 (0.00%)	1 / 18 (5.56%)	0 / 81 (0.00%)	1 / 45 (2.22%)	2 / 86 (2.33%)	0 / 43 (0.00%)
occurrences all number	2	0	1	0	3	4	0
hypoalbuminaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	3 / 18 (16.67%)	8 / 81 (9.88%)	4 / 45 (8.89%)	2 / 86 (2.33%)	5 / 43 (11.63%)
occurrences all number	1	0	4	9	6	3	7
hypocalcaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	0 / 21 (0.00%)	0 / 15 (0.00%)	4 / 18 (22.22%)	5 / 81 (6.17%)	4 / 45 (8.89%)	1 / 86 (1.16%)	3 / 43 (6.98%)
occurrences all number	0	0	4	6	5	1	5
hypokalaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	1 / 15 (6.67%)	5 / 18 (27.78%)	6 / 81 (7.41%)	9 / 45 (20.00%)	10 / 86 (11.63%)	7 / 43 (16.28%)
occurrences all number	2	1	10	10	16	24	14
hypomagnesaemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	1 / 18 (5.56%)	1 / 81 (1.23%)	3 / 45 (6.67%)	3 / 86 (3.49%)	3 / 43 (6.98%)
occurrences all number	1	0	1	1	5	5	7
hyponatraemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	1 / 21 (4.76%)	0 / 15 (0.00%)	3 / 18 (16.67%)	4 / 81 (4.94%)	2 / 45 (4.44%)	2 / 86 (2.33%)	1 / 43 (2.33%)
occurrences all number	8	0	4	7	2	7	1
hypophosphataemia
alternative dictionary used: MedDRA 21.0
subjects affected / exposed	2 / 21 (9.52%)	0 / 15 (0.00%)	1 / 18 (5.56%)	2 / 81 (2.47%)	1 / 45 (2.22%)	4 / 86 (4.65%)	2 / 43 (4.65%)
occurrences all number	2	0	1	6	1	8	4

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.

More information

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Were there any global substantial amendments to the protocol? Yes

15 Jun 2016

The rationale for amendment (a) was based on feedback received from global regulatory authorities and compliance with local regulatory requirements for submissions. Major changes for amendment (a) included the following: new descriptive language on premedication prior to olaratumab/placebo doses on Days 1 and 8 of Cycle 1 and in subsequent cycles. Clarification was also added related to the olaratumab observation period.

05 Jan 2017

Amendment (b): The protocol was amended to allow for expansion of the olaratumab 20 mg/kg dose level (Cohort 2) by enrolling approximately 15 additional patients. The rationale for adding an additional 15 patients to Cohort 2 is to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 randomized double-blinded portion of the trial.

19 Jul 2017

Amendment (c): The protocol was amended to enroll an additional cohort of 90 patients previously treated with olaratumab in combination with doxorubicin, in order to evaluate, as secondary objective, the effect of olaratumab as continuation therapy with regimens such as gemcitabine/docetaxel that are customarily administered after maximal doxorubicin dosing. The protocol amendment also added an interim efficacy analysis of all study outcomes.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 1b (Open-Label) / Phase 2 (Randomized, Double-Blinded) Study Evaluating Gemcitabine and Docetaxel With or Without Olaratumab in the Treatment of Advanced Soft Tissue Sarcoma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase 1b: Number of Participants with Dose Limiting Toxicity (DLT)

Primary: Phase 1b: Number of Participants with Dose Limiting Toxicity (DLT)

Primary: Phase 2: Overall Survival (OS) (Olaratumab-Naive)

Primary: Phase 2: Overall Survival (OS) (Olaratumab-Naive)

Secondary: Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab

Secondary: Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab

Secondary: Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab

Secondary: Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab

Secondary: Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab

Secondary: Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab

Secondary: Phase 1b/2: PK: Cmax of Gemcitabine

Secondary: Phase 1b/2: PK: Cmax of Gemcitabine

Secondary: Phase 1b/2: PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Gemcitabine

Secondary: Phase 1b/2: PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Gemcitabine

Secondary: Phase 1b/2: PK: Cmax of Docetaxel

Secondary: Phase 1b/2: PK: Cmax of Docetaxel

Secondary: Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Docetaxel

Secondary: Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Docetaxel

Secondary: Phase 1b/2: Population PK: Clearance of Olaratumab

Secondary: Phase 1b/2: Population PK: Clearance of Olaratumab

Secondary: Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab

Secondary: Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab

Secondary: Phase 2: Overall Survival (Olaratumab Pre-Treated)

Secondary: Phase 2: Overall Survival (Olaratumab Pre-Treated)

Secondary: Phase 2: Progression Free Survival (PFS)

Secondary: Phase 2: Progression Free Survival (PFS)

Secondary: Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR])

Secondary: Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR])

Secondary: Phase 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD)

Secondary: Phase 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD)

Secondary: Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"

Secondary: Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"

Secondary: Phase 2: Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Symptom Scales.

Secondary: Phase 2: Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Symptom Scales.

Secondary: Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)

Secondary: Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)

Secondary: Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies

Secondary: Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 1b (Open-Label) / Phase 2 (Randomized, Double-Blinded) Study Evaluating Gemcitabine and Docetaxel With or Without Olaratumab in the Treatment of Advanced Soft Tissue Sarcoma