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Clinical Trial Results:
An Open-Label, Phase Ia/Ib/IIa Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or an LHRH Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

Summary
EudraCT number	2014-004852-77
Trial protocol	ES NL
Global end of trial date	13 Mar 2020

Results information
Results version number	v1(current)
This version publication date	11 Mar 2021
First version publication date	11 Mar 2021
Other versions

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

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Trial information

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Sponsor protocol code

GO29642

ISRCTN number

US NCT number

NCT01823835

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

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

19 Nov 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

13 Mar 2020

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary objectives of this study were to assess the safety, tolerability and anti-tumor activity of GDC-0810 in women with locally advanced or metastatic ER+ (HER2−) breast cancer.

Protection of trial subjects

All study subjects were required to read and sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

03 Apr 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 141

Country: Number of subjects enrolled

Netherlands: 2

Country: Number of subjects enrolled

Korea, Republic of: 3

Country: Number of subjects enrolled

Spain: 6

Worldwide total number of subjects

152

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

152 participants were enrolled into Phase I/IIa/Ib of the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Phase Ia – Cohort 1

Arm description

100 mg GDC-0810 once daily (QD) in fasting state.

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

100 mg GDC-0810 once daily (QD) in fasting state.

Phase Ia – Cohort 2

Arm description

200 mg GDC-0810 QD in fasting state.

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg GDC-0810 QD in fasting state.

Phase Ia – Cohort 3

Arm description

400 mg GDC-0810 QD in fasting state.

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

400 mg GDC-0810 QD in fasting state.

Phase Ia – Cohort 4

Arm description

600 mg GDC-0810 QD in fasting state.

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

600 mg GDC-0810 QD in fasting state.

Phase Ia – Cohort 5

Arm description

600 mg GDC-0810 QD in non-fasting state.

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

600 mg GDC-0810 QD in non-fasting state.

Phase Ia – Cohort 6

Arm description

300 mg GDC-0810 twice daily (BID) in fasting state.

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

300 mg GDC-0810 twice daily (BID) in fasting state.

Phase Ia – Cohort 7

Arm description

800 mg GDC-0810 QD in fasting state.

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

800 mg GDC-0810 QD in fasting state.

Phase Ia – Cohort 8

Arm description

800 mg GDC-0810 QD in non-fasting state.

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

800 mg GDC-0810 QD in non-fasting state.

Phase Ia – Cohort 9

Arm description

400 mg GDC-0810 BID in fasting state.

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

400 mg GDC-0810 BID in fasting state.

Phase IIa – Cohort A1

Arm description

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had confirmed ER-a (ESR1) mutation of the ligand binding domain (LBD).

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

600 mg GDC-0810 QD.

Phase IIa – Cohort A2

Arm description

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and confirmed ER-a (ESR1) mutation of the LBD.

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

600 mg GDC-0810 QD.

Phase IIa – Cohort B1

Arm description

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had progressed following ≤1 prior therapy with an aromatase inhibitor (AI).

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

600 mg GDC-0810 QD.

Phase IIa – Cohort B2

Arm description

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and progressed following ≤1 prior therapy with an AI.

Arm type

Experimental

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

600 mg GDC-0810 QD.

Phase Ib – Cohort C1

Arm description

400 mg GDC-0810 + 125 mg Palbociclib QD.

Arm type

Experimental

Investigational medicinal product name

Palbociclib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

125 mg Palbociclib QD.

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

400 mg GDC-0810 QD.

Phase Ib – Cohort D1

Arm description

≤600 mg GDC-0810 QD + LHRH agonist once monthly.

Arm type

Experimental

Investigational medicinal product name

Luteinizing Hormone Releasing Hormone (LHRH) Agonist

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

LHRH agonist will be administered once monthly until disease progression, unacceptable toxicity, or withdrawal of consent

Investigational medicinal product name

GDC-0810

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

≤600 mg GDC-0810 QD.

Number of subjects in period 1	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9	Phase IIa – Cohort A1	Phase IIa – Cohort A2	Phase IIa – Cohort B1	Phase IIa – Cohort B2	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Started	3	4	4	6	6	6	6	3	3	19	10	53	19	4	6
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	3	4	4	6	6	6	6	3	3	19	10	53	19	4	6
Consent withdrawn by subject	-	-	1	-	-	-	-	-	-	1	1	2	1	-	-
Physician decision	-	-	-	-	-	-	-	-	-	-	-	2	-	-	-
Study Termination	-	-	-	-	1	-	-	-	-	-	-	1	-	-	-
Adverse event, non-fatal	-	-	-	-	1	-	1	-	-	-	1	2	-	-	-
Progressive Disease	3	4	3	6	4	6	5	3	3	18	8	46	18	4	6

Baseline characteristics

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Reporting group title

Phase Ia – Cohort 1

Reporting group description

100 mg GDC-0810 once daily (QD) in fasting state.

Reporting group title

Phase Ia – Cohort 2

Reporting group description

200 mg GDC-0810 QD in fasting state.

Reporting group title

Phase Ia – Cohort 3

Reporting group description

400 mg GDC-0810 QD in fasting state.

Reporting group title

Phase Ia – Cohort 4

Reporting group description

600 mg GDC-0810 QD in fasting state.

Reporting group title

Phase Ia – Cohort 5

Reporting group description

600 mg GDC-0810 QD in non-fasting state.

Reporting group title

Phase Ia – Cohort 6

Reporting group description

300 mg GDC-0810 twice daily (BID) in fasting state.

Reporting group title

Phase Ia – Cohort 7

Reporting group description

800 mg GDC-0810 QD in fasting state.

Reporting group title

Phase Ia – Cohort 8

Reporting group description

800 mg GDC-0810 QD in non-fasting state.

Reporting group title

Phase Ia – Cohort 9

Reporting group description

400 mg GDC-0810 BID in fasting state.

Reporting group title

Phase IIa – Cohort A1

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had confirmed ER-a (ESR1) mutation of the ligand binding domain (LBD).

Reporting group title

Phase IIa – Cohort A2

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and confirmed ER-a (ESR1) mutation of the LBD.

Reporting group title

Phase IIa – Cohort B1

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had progressed following ≤1 prior therapy with an aromatase inhibitor (AI).

Reporting group title

Phase IIa – Cohort B2

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and progressed following ≤1 prior therapy with an AI.

Reporting group title

Phase Ib – Cohort C1

Reporting group description

400 mg GDC-0810 + 125 mg Palbociclib QD.

Reporting group title

Phase Ib – Cohort D1

Reporting group description

≤600 mg GDC-0810 QD + LHRH agonist once monthly.

Reporting group values	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9	Phase IIa – Cohort A1	Phase IIa – Cohort A2	Phase IIa – Cohort B1	Phase IIa – Cohort B2	Phase Ib – Cohort C1	Phase Ib – Cohort D1	Total
Number of subjects	3	4	4	6	6	6	6	3	3	19	10	53	19	4	6	152
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	1	2	3	5	1	4	4	3	1	15	4	28	10	3	6	90
From 65-84 years	2	2	1	1	5	2	2	0	2	4	6	25	9	1	0	62
85 years and over	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	66.3 ( 5.7 )	63.5 ( 9.6 )	60.8 ( 6.9 )	55.3 ( 8.5 )	69.3 ( 7.2 )	56.2 ( 12.8 )	50.5 ( 14.6 )	58.3 ( 3.5 )	64.7 ( 4.0 )	55.4 ( 12.2 )	63.4 ( 8.9 )	61.9 ( 9.3 )	62.6 ( 12.2 )	58.5 ( 13.1 )	41.7 ( 8.9 )	-
Sex: Female, Male
Units:
Female	3	4	4	6	6	6	6	3	3	19	10	53	19	4	6	152
Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Race/Ethnicity, Customized
Units: Subjects
Asian	0	0	0	0	1	1	0	0	0	2	1	2	0	0	3	10
Black or African American	0	0	1	0	0	0	0	0	0	0	0	0	2	0	0	3
White	2	4	3	6	5	4	6	3	3	17	8	46	15	4	1	127
Other	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Unknown	0	0	0	0	0	1	0	0	0	0	1	5	2	0	2	11

End points

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Reporting group title

Phase Ia – Cohort 1

Reporting group description

100 mg GDC-0810 once daily (QD) in fasting state.

Reporting group title

Phase Ia – Cohort 2

Reporting group description

200 mg GDC-0810 QD in fasting state.

Reporting group title

Phase Ia – Cohort 3

Reporting group description

400 mg GDC-0810 QD in fasting state.

Reporting group title

Phase Ia – Cohort 4

Reporting group description

600 mg GDC-0810 QD in fasting state.

Reporting group title

Phase Ia – Cohort 5

Reporting group description

600 mg GDC-0810 QD in non-fasting state.

Reporting group title

Phase Ia – Cohort 6

Reporting group description

300 mg GDC-0810 twice daily (BID) in fasting state.

Reporting group title

Phase Ia – Cohort 7

Reporting group description

800 mg GDC-0810 QD in fasting state.

Reporting group title

Phase Ia – Cohort 8

Reporting group description

800 mg GDC-0810 QD in non-fasting state.

Reporting group title

Phase Ia – Cohort 9

Reporting group description

400 mg GDC-0810 BID in fasting state.

Reporting group title

Phase IIa – Cohort A1

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had confirmed ER-a (ESR1) mutation of the ligand binding domain (LBD).

Reporting group title

Phase IIa – Cohort A2

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and confirmed ER-a (ESR1) mutation of the LBD.

Reporting group title

Phase IIa – Cohort B1

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had progressed following ≤1 prior therapy with an aromatase inhibitor (AI).

Reporting group title

Phase IIa – Cohort B2

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and progressed following ≤1 prior therapy with an AI.

Reporting group title

Phase Ib – Cohort C1

Reporting group description

400 mg GDC-0810 + 125 mg Palbociclib QD.

Reporting group title

Phase Ib – Cohort D1

Reporting group description

≤600 mg GDC-0810 QD + LHRH agonist once monthly.

Primary: Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent

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End point title

Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent ^[1] ^[2]

End point description

Maximum Tolerated Dose (MTD) is determined based on the number of Dose Limiting Toxicities (DLTs) experienced by the participants. DLTs were defined as any of the following adverse events (AEs) that are deemed by the investigator or the Sponsor to be related to study drug (toxicities will be attributed to single agent GDC-0810 unless they are clearly related to disease progression or can clearly be attributed to a cause other than GDC-0810 administration): - Any grade ≥ 3 non-hematologic toxicity (excluding alopecia) - Any grade ≥ 3 hematologic toxicity of > 7 days’ duration - Any grade toxicity that leads to study drug interruption of > 7 days’ duration

End point type

Primary

End point timeframe

Day -7 through the first cycle (28 days) of treatment (35 days total)

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 statistical analyses 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9
Number of subjects analysed	0 ^[3]	0 ^[4]	0 ^[5]	0 ^[6]	0 ^[7]	0 ^[8]	0 ^[9]	0 ^[10]	0 ^[11]
Units: milligram (mg)
number (not applicable)

Notes
[3] - The MTD could not be determined.
[4] - The MTD could not be determined.
[5] - The MTD could not be determined.
[6] - The MTD could not be determined.
[7] - The MTD could not be determined.
[8] - The MTD could not be determined.
[9] - The MTD could not be determined.
[10] - The MTD could not be determined.
[11] - The MTD could not be determined.

No statistical analyses for this end point

Primary: Phase Ia: Recommended Phase II Dose (RP2D) of GDC-0810 When Used as a Single Agent

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End point title

Phase Ia: Recommended Phase II Dose (RP2D) of GDC-0810 When Used as a Single Agent ^[12] ^[13]

End point description

End point type

Primary

End point timeframe

Day -7 through the first cycle (28 days) of treatment (35 days total)

Notes
[12] - 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 statistical analyses were planned for this endpoint.
[13] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9
Number of subjects analysed	3	4	4	6	6	6	6	3	3
Units: milligram (mg)
number (not applicable)	600	600	600	600	600	600	600	600	600

No statistical analyses for this end point

Primary: Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1

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End point title

Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1 ^[14] ^[15]

End point description

Objective response (OR) is defined as a complete response (CR) or partial response (PR) as determined by investigator assessment according to RECIST v1.1. OR was based on criteria related to changes in size of target lesions. CR was the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

End point type

Primary

End point timeframe

Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years)

Notes
[14] - 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 statistical analyses were planned for this endpoint.
[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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase IIa – Cohort A1	Phase IIa – Cohort A2	Phase IIa – Cohort B1	Phase IIa – Cohort B2
Number of subjects analysed	19	10	53	19
Units: percentage of participants
number (not applicable)
Complete Response	0	0	0	0
Partial Response	0	0	7.5	0

No statistical analyses for this end point

Primary: Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

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End point title

Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) ^[16] ^[17]

End point description

Clinical Benefit Response (CBR) is defined as the percentage of participants achieving confirmed RECIST v1.1 defined CR, PR, and/or stable disease. CR was the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.

End point type

Primary

End point timeframe

Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years)

Notes
[16] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.
[17] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase IIa – Cohort A1	Phase IIa – Cohort A2	Phase IIa – Cohort B1	Phase IIa – Cohort B2
Number of subjects analysed	19	10	53	19
Units: percentage of participants
number (not applicable)	5.3	10.0	28.3	15.8

No statistical analyses for this end point

Primary: Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH

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End point title

Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH ^[18] ^[19]

End point description

End point type

Primary

End point timeframe

first cycle (Days 1 to 28 of a 28-day schedule)

Notes
[18] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.
[19] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[20]	0 ^[21]
Units: mg

Notes
[20] - Data not available due to the discontinuation of GDC-0810 development.
[21] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: All Phases: Percentage of Participants With Adverse Events (AEs)

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End point title

All Phases: Percentage of Participants With Adverse Events (AEs)

End point description

End point type

Secondary

End point timeframe

up to 3 years

End point values	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9	Phase IIa – Cohort A1	Phase IIa – Cohort A2	Phase IIa – Cohort B1	Phase IIa – Cohort B2	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	3	4	4	6	6	6	6	3	3	19	10	53	19	4	6
Units: percentage of participants	100	100	100	100	100	100	100	100	100	100	100	100	100	100	100

No statistical analyses for this end point

Secondary: Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

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End point title

Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites ^[22]

End point description

Maximum Plasma Concentration (Cmax) has been calculated following oral administration of single and multiple doses (at steady state) of GDC-0810. Here 99999 represents data that were not available.

End point type

Secondary

End point timeframe

Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 (Day -6), and 48 (Day -5) hours postdose; Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose (Cycle 2 Day 2, prior to the next dose)

Notes
[22] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9
Number of subjects analysed	3	4	4	6	6	6	6	3	3
Units: micrograms per milliliter (ug/mL)
arithmetic mean (standard deviation)
GDC-0810 (Single Dose)	2.29 ( 1.24 )	3.76 ( 0.599 )	9.4 ( 2.53 )	12.7 ( 5.36 )	22.2 ( 11.6 )	9.73 ( 4.5 )	15.9 ( 3.13 )	15.6 ( 4.97 )	10.1 ( 4.23 )
GDC-0810 (Multiple Doses)	2.59 ( 1.43 )	3.26 ( 1.11 )	9.08 ( 3.43 )	11.8 ( 6.61 )	25 ( 8.35 )	8.89 ( 3.96 )	18.4 ( 4.84 )	25.5 ( 9.3 )	13.9 ( 4.87 )
GDC-0810-N-Glucuronide (Single Dose)	0.0171 ( 0.021 )	0.0535 ( 0.015 )	0.177 ( 0.1 )	0.468 ( 0.388 )	0.691 ( 0.526 )	0.299 ( 0.171 )	1.38 ( 1.19 )	0.369 ( 0.338 )	0.153 ( 0.0421 )
GDC-0810-N-Glucuronide (Multiple Doses)	0.067 ( 0.055 )	0.061 ( 0.0271 )	0.184 ( 0.0832 )	0.416 ( 0.346 )	0.723 ( 0.338 )	0.181 ( 0.0846 )	0.74 ( 0.327 )	1.17 ( 0.893 )	0.308 ( 0.148 )
GDC-0810-Acyl-Glucuronide (Single Dose)	99999 ( 99999 )	99999 ( 99999 )	1.46 ( 0.997 )	3 ( 0.827 )	2.26 ( 1.24 )	1.35 ( 0.876 )	7.02 ( 8.19 )	1.29 ( 0.617 )	1.36 ( 0.421 )
GDC-0810-Acyl-Glucuronide (Multiple Doses)	99999 ( 99999 )	99999 ( 99999 )	1.89 ( 1.34 )	3.64 ( 2.96 )	3.16 ( 1.2 )	0.993 ( 0.435 )	3.37 ( 2.34 )	4.62 ( 2.19 )	2.82 ( 1.43 )

No statistical analyses for this end point

Secondary: Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

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End point title

Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites ^[23]

End point description

Time to Maximum Concentration (Tmax) has been calculated following oral administration of single and multiple doses (at steady state) of GDC-0810. Here 99999 represents data that were not available.

End point type

Secondary

End point timeframe

Notes
[23] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9
Number of subjects analysed	3	4	4	6	6	6	6	3	3
Units: hour (hr)
median (full range (min-max))
GDC-0810 (Single Dose)	1.5 (1.5 to 2)	1.71 (1.45 to 2)	2 (1 to 3)	2.99 (1.25 to 4)	3.01 (1.5 to 6)	1.48 (0.217 to 3.03)	3.04 (2.17 to 4)	2 (2 to 4.07)	1.88 (1 to 3)
GDC-0810 (Multiple Doses)	1.47 (0.95 to 2)	0.9 (0.45 to 1)	1.55 (1.07 to 1.68)	2.48 (1.93 to 6.45)	2.95 (1.95 to 4.03)	1.65 (0.917 to 3.07)	1.59 (1.08 to 1.92)	2.93 (1.53 to 6.3)	2.05 (1.47 to 2.42)
GDC-0810-N-Glucuronide (Single Dose)	0.5 (0.5 to 1.5)	1.95 (1.5 to 2)	2 (1.52 to 3)	2.85 (2 to 4)	3.51 (1.5 to 6.07)	1.72 (0.217 to 3.03)	3.54 (3 to 4)	3 (2 to 4.07)	1.88 (1 to 3)
GDC-0810-N-Glucuronide (Multiple Doses)	2 (0 to 2.05)	1 (0.9 to 1.48)	1.64 (1.52 to 2.08)	3.49 (1.93 to 4.45)	2.95 (1.95 to 4.03)	1.65 (0.917 to 3.07)	2.27 (1.08 to 3.03)	2.93 (1.53 to 6.3)	2.05 (1.47 to 3.37)
GDC-0810-Acyl-Glucuronide (Single Dose)	99999 (99999 to 99999)	99999 (99999 to 99999)	2 (1.52 to 3)	2.85 (2.72 to 2.98)	3.51 (2 to 6.07)	1.98 (0.717 to 3.03)	3.54 (3 to 4)	3 (2 to 4.07)	2.98 (1 to 3)
GDC-0810-Acyl-Glucuronide (Multiple Doses)	99999 (99999 to 99999)	99999 (99999 to 99999)	1.84 (1.52 to 2.17)	3.53 (3.07 to 4)	2.95 (1.95 to 4.03)	1.65 (0.917 to 3.07)	2.27 (1.08 to 3.03)	2.93 (1.53 to 6.3)	2.05 (2 to 3.37)

No statistical analyses for this end point

Secondary: Phase Ia: Area Under the Concentration-time Curves at 6 hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites

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End point title

Phase Ia: Area Under the Concentration-time Curves at 6 hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites ^[24]

End point description

Here 99999 represents data that were not available.

End point type

Secondary

End point timeframe

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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9
Number of subjects analysed	3	4	4	6	6	6	6	3	3
Units: hr*ug/mL
arithmetic mean (standard deviation)
GDC-0810 (Single Dose)	3.18 ( 1.65 )	6.78 ( 1.19 )	23.7 ( 11.3 )	34.3 ( 14.4 )	58.2 ( 28.9 )	18.8 ( 7.38 )	51.1 ( 18 )	48.3 ( 28.4 )	22.1 ( 5.43 )
GDC-0810 (Multiple Doses)	4.83 ( 2.3 )	6.19 ( 2.18 )	18.8 ( 4.76 )	41.1 ( 27.5 )	74.9 ( 30.1 )	19.3 ( 7.01 )	65.7 ( 20.6 )	70.5 ( 22 )	43 ( 26 )
GDC-0810-N-Glucuronide (Single Dose)	0.0401 ( 0.0197 )	0.116 ( 0.0729 )	0.321 ( 0.149 )	1.16 ( 0.815 )	1.36 ( 0.917 )	0.486 ( 0.36 )	3.81 ( 4.15 )	0.938 ( 0.983 )	0.29 ( 0.0295 )
GDC-0810-N-Glucuronide (Multiple Doses)	0.105 ( 0.0724 )	0.103 ( 0.0335 )	0.321 ( 0.105 )	1.37 ( 1.21 )	1.83 ( 1.01 )	0.409 ( 0.23 )	2.63 ( 1.01 )	2.08 ( 1.15 )	0.974 ( 0.605 )
GDC-0810-Acyl-Glucuronide (Single Dose)	99999 ( 99999 )	99999 ( 99999 )	3.18 ( 1.77 )	8.25 ( 4.54 )	5.29 ( 2.71 )	2.76 ( 2.23 )	21.1 ( 26.9 )	3.99 ( 2.29 )	3.27 ( 1.03 )
GDC-0810-Acyl-Glucuronide (Multiple Doses)	99999 ( 99999 )	99999 ( 99999 )	3.72 ( 1.91 )	13 ( 11.1 )	8.25 ( 3.47 )	2.03 ( 0.669 )	14 ( 11.1 )	10.2 ( 3.61 )	8.45 ( 5.79 )

No statistical analyses for this end point

Secondary: Phase Ia: Area Under the Concentration-time Curves at 24 hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites

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End point title

Phase Ia: Area Under the Concentration-time Curves at 24 hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites ^[25]

End point description

Here 99999 represents data that were not available.

End point type

Secondary

End point timeframe

Notes
[25] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9
Number of subjects analysed	3	4	4	6	6	6	6	3	3
Units: hr*ug/mL
arithmetic mean (standard deviation)
GDC-0810 (Single Dose)	3.58 ( 1.75 )	8.81 ( 2.52 )	28.5 ( 15.6 )	44.7 ( 19.5 )	101 ( 49.9 )	41.2 ( 15.9 )	61.8 ( 25.5 )	95.1 ( 76.4 )	47.7 ( 11.4 )
GDC-0810 (Multiple Doses)	5.34 ( 2.99 )	7.36 ( 1.32 )	22.8 ( 6.14 )	66.9 ( 46.8 )	102 ( 35.9 )	44.2 ( 14.5 )	80.4 ( 26.8 )	75.2 ( 15.4 )	109 ( 73.3 )
GDC-0810-N-Glucuronide (Single Dose)	0.13 ( 0.0197 )	0.224 ( 0.109 )	0.413 ( 0.152 )	1.54 ( 1.08 )	2.08 ( 1.02 )	1.07 ( 0.786 )	5.67 ( 7.17 )	1.83 ( 2.04 )	0.649 ( 0.055 )
GDC-0810-N-Glucuronide (Multiple Doses)	0.13 ( 0.0141 )	0.132 ( 0.0253 )	0.413 ( 0.121 )	2.63 ( 2.21 )	2.64 ( 1.4 )	1.09 ( 0.594 )	3.72 ( 1.81 )	2.35 ( 1.57 )	2.66 ( 1.58 )
GDC-0810-Acyl-Glucuronide (Single Dose)	99999 ( 99999 )	99999 ( 99999 )	3.76 ( 2.13 )	11.4 ( 7.43 )	8.59 ( 3.82 )	6.03 ( 4.89 )	30.6 ( 44 )	7.64 ( 5.51 )	7.1 ( 1.96 )
GDC-0810-Acyl-Glucuronide (Multiple Doses)	99999 ( 99999 )	99999 ( 99999 )	4.42 ( 2.27 )	21.8 ( 21.2 )	10.4 ( 4.07 )	4.61 ( 1.34 )	18.1 ( 16.3 )	12 ( 5.44 )	20.8 ( 14.9 )

No statistical analyses for this end point

Secondary: Area under the concentration–time curve from Time 0 to infinity (AUC0-Inf)

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End point title

Area under the concentration–time curve from Time 0 to infinity (AUC0-Inf) ^[26]

End point description

Here 999999 represents data that were not estimable.

End point type

Secondary

End point timeframe

Notes
[26] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9
Number of subjects analysed	3	4	4	5	6	6	4	3	3
Units: hr*ug/ml
arithmetic mean (standard deviation)	5.3 ( 1.96 )	10 ( 2.8 )	30.8 ( 16.3 )	40.5 ( 11.3 )	114 ( 57.4 )	999999 ( 999999 )	65.7 ( 28 )	101 ( 78.5 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent

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End point title

Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent ^[27]

End point description

Half-life (t1/2) was calculated after single dose administration and not at steady state. Here 999999 represents data that were not estimable.

End point type

Secondary

End point timeframe

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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9
Number of subjects analysed	3	4	4	5	6	6	4	3	3
Units: hr
arithmetic mean (standard deviation)	40.7 ( 3.47 )	15.2 ( 2.35 )	24.1 ( 17.3 )	9.58 ( 3.41 )	7.91 ( 2.67 )	999999 ( 999999 )	10.1 ( 1.59 )	7.09 ( 3.23 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase Ia: Apparent Clearance (Cl/F)

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End point title

Phase Ia: Apparent Clearance (Cl/F) ^[28]

End point description

Here 999999 represents data that were not estimable.

End point type

Secondary

End point timeframe

Notes
[28] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ia – Cohort 1	Phase Ia – Cohort 2	Phase Ia – Cohort 3	Phase Ia – Cohort 4	Phase Ia – Cohort 5	Phase Ia – Cohort 6	Phase Ia – Cohort 7	Phase Ia – Cohort 8	Phase Ia – Cohort 9
Number of subjects analysed	3	4	4	5	6	6	4	3	3
Units: L/hr
arithmetic mean (standard deviation)	20.4 ( 6.43 )	21 ( 4.94 )	15.1 ( 5.56 )	15.7 ( 4.13 )	8.21 ( 8.38 )	999999 ( 999999 )	15.1 ( 9.45 )	11.1 ( 6.23 )	999999 ( 999999 )

No statistical analyses for this end point

Secondary: Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula

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End point title

Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula ^[29]

End point description

End point type

Secondary

End point timeframe

Screening; on Cycle 2 Day 1 predose and at 1, 2, 3, 4, and 6 hours postdose; Cycle 3 Day 1 predose, and at 1, 3, and 6 hours post dose

Notes
[29] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase IIa – Cohort A1	Phase IIa – Cohort A2	Phase IIa – Cohort B1	Phase IIa – Cohort B2
Number of subjects analysed	19	10	53	19
Units: percentage of participants
number (not applicable)
≤ 450 milliseconds (msec)	100	66.7	91.2	100
>450 and ≤480 msec	0	33.3	8.8	0
Increase from baseline ≤30 msec	100	100	93.9	100
Increase from baseline >30 and ≤60 msec	0	0	6.1	0

No statistical analyses for this end point

Secondary: Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

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End point title

Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist ^[30]

End point description

Here 999999 represents data that were not estimable.

End point type

Secondary

End point timeframe

Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (Cohorts C1 and D1), Cycle 1 Day 8 (Cohort C1), and Cycle 2 Day 1 (Cohort D1)

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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[31]	0 ^[32]
Units: ug/ml
arithmetic mean (standard deviation)	( )	( )

Notes
[31] - Data not available due to the discontinuation of GDC-0810 development.
[32] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

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End point title

Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist ^[33]

End point description

End point type

Secondary

End point timeframe

Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (Cohorts C1 and D1), Cycle 1 Day 8 (Cohort C1), and Cycle 2 Day 1 (Cohort D1)

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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[34]	0 ^[35]
Units: hr
median (full range (min-max))	( to )	( to )

Notes
[34] - Data not available due to the discontinuation of GDC-0810 development.
[35] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: Phase Ib: AUC of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

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End point title

Phase Ib: AUC of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist ^[36]

End point description

End point type

Secondary

End point timeframe

Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (Cohorts C1 and D1), Cycle 1 Day 8 (Cohort C1), and Cycle 2 Day 1 (Cohort D1)

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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[37]	0 ^[38]
Units: hr*ug/ml
arithmetic mean (standard deviation)	( )	( )

Notes
[37] - Data not available due to the discontinuation of GDC-0810 development.
[38] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: Phase Ib: t/2 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

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End point title

Phase Ib: t/2 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist ^[39]

End point description

End point type

Secondary

End point timeframe

Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (Cohorts C1 and D1), Cycle 1 Day 8 (Cohort C1), and Cycle 2 Day 1 (Cohort D1)

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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[40]	0 ^[41]
Units: hr
arithmetic mean (standard deviation)	( )	( )

Notes
[40] - Data not available due to the discontinuation of GDC-0810 development.
[41] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

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End point title

Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist ^[42]

End point description

End point type

Secondary

End point timeframe

Cohort C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Notes
[42] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[43]	0 ^[44]
Units: ug/ml
arithmetic mean (standard deviation)	( )	( )

Notes
[43] - Data not available due to the discontinuation of GDC-0810 development.
[44] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

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End point title

Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist ^[45]

End point description

End point type

Secondary

End point timeframe

Cohort C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Notes
[45] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[46]	0 ^[47]
Units: hr
median (full range (min-max))	( to )	( to )

Notes
[46] - Data not available due to the discontinuation of GDC-0810 development.
[47] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: Phase Ib: AUC of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

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End point title

Phase Ib: AUC of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist ^[48]

End point description

End point type

Secondary

End point timeframe

Cohort C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Notes
[48] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[49]	0 ^[50]
Units: hr*ug/ml
arithmetic mean (standard deviation)	( )	( )

Notes
[49] - Data not available due to the discontinuation of GDC-0810 development.
[50] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

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End point title

Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist ^[51]

End point description

End point type

Secondary

End point timeframe

Cohort C1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8

Notes
[51] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[52]	0 ^[53]
Units: hr
arithmetic mean (standard deviation)	( )	( )

Notes
[52] - Data not available due to the discontinuation of GDC-0810 development.
[53] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

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End point title

Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib ^[54]

End point description

End point type

Secondary

End point timeframe

Cohort D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Notes
[54] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[55]	0 ^[56]
Units: ug/ml
arithmetic mean (standard deviation)	( )	( )

Notes
[55] - Data not available due to the discontinuation of GDC-0810 development.
[56] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

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End point title

Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib ^[57]

End point description

End point type

Secondary

End point timeframe

Cohort D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Notes
[57] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[58]	0 ^[59]
Units: hr
arithmetic mean (standard deviation)	( )	( )

Notes
[58] - Data not available due to the discontinuation of GDC-0810 development.
[59] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: Phase Ib: AUC of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib

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End point title

Phase Ib: AUC of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib ^[60]

End point description

End point type

Secondary

End point timeframe

Cohort D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Notes
[60] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[61]	0 ^[62]
Units: hr*ug/ml
arithmetic mean (standard deviation)	( )	( )

Notes
[61] - Data not available due to the discontinuation of GDC-0810 development.
[62] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Secondary: Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

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End point title

Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib ^[63]

End point description

End point type

Secondary

End point timeframe

Cohort D1: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1

Notes
[63] - 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: This endpoint was specific to participants in the relevant arm of the specific phase of the study.

End point values	Phase Ib – Cohort C1	Phase Ib – Cohort D1
Number of subjects analysed	0 ^[64]	0 ^[65]
Units: hr
arithmetic mean (standard deviation)	( )	( )

Notes
[64] - Data not available due to the discontinuation of GDC-0810 development.
[65] - Data not available due to the discontinuation of GDC-0810 development.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

up to 3 years

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Phase Ia – Cohort 1

Reporting group description

100 mg GDC-0810 once daily (QD) in fasting state.

Reporting group title

Phase Ia - Cohort 2

Reporting group description

200 mg GDC-0810 QD in fasting state

Reporting group title

Phase Ia – Cohort 6

Reporting group description

300 mg GDC-0810 twice daily (BID) in fasting state.

Reporting group title

Phase Ia – Cohort 3

Reporting group description

400 mg GDC-0810 QD in fasting state.

Reporting group title

Phase Ia – Cohort 9

Reporting group description

400 mg GDC-0810 BID in fasting state.

Reporting group title

Phase Ia – Cohort 5

Reporting group description

600 mg GDC-0810 QD in non-fasting state.

Reporting group title

Phase Ia – Cohort 4

Reporting group description

600 mg GDC-0810 QD in fasting state.

Reporting group title

Phase Ia – Cohort 8

Reporting group description

800 mg GDC-0810 QD in non-fasting state.

Reporting group title

Phase Ia – Cohort 7

Reporting group description

800 mg GDC-0810 QD in fasting state.

Reporting group title

Phase IIa – Cohort A1

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had confirmed ER-a (ESR1) mutation of the ligand binding domain (LBD).

Reporting group title

Phase IIa – Cohort A2

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and confirmed ER-a (ESR1) mutation of the LBD.

Reporting group title

Phase IIa – Cohort B2

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm had prior treatment with fulvestrant and progressed following ≤1 prior therapy with an AI.

Reporting group title

Phase IIa – Cohort B1

Reporting group description

600 mg GDC-0810 QD. Additionally, participants in this arm did not receive any prior treatment with fulvestrant and had progressed following ≤1 prior therapy with an aromatase inhibitor (AI).

Reporting group title

Phase Ib – Cohort D1

Reporting group description

≤600 mg GDC-0810 QD + LHRH agonist once monthly.

Reporting group title

Phase Ib – Cohort C1

Reporting group description

400 mg GDC-0810 + 125 mg Palbociclib QD.

Phase Ia – Cohort 1

Phase Ia - Cohort 2

Phase Ia – Cohort 6

Phase Ia – Cohort 3

Phase Ia – Cohort 9

Phase Ia – Cohort 5

Phase Ia – Cohort 4

Phase Ia – Cohort 8

Phase Ia – Cohort 7

Phase IIa – Cohort A1

Phase IIa – Cohort A2

Phase IIa – Cohort B2

Phase IIa – Cohort B1

Phase Ib – Cohort D1

Phase Ib – Cohort C1

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 3 (33.33%)

1 / 4 (25.00%)

4 / 6 (66.67%)

1 / 4 (25.00%)

0 / 3 (0.00%)

3 / 6 (50.00%)

1 / 6 (16.67%)

1 / 3 (33.33%)

1 / 6 (16.67%)

4 / 19 (21.05%)

1 / 10 (10.00%)

1 / 19 (5.26%)

11 / 53 (20.75%)

2 / 6 (33.33%)

1 / 4 (25.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

BREAST CANCER

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

2 / 53 (3.77%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

TUMOUR PAIN

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

DEEP VEIN THROMBOSIS

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HYPERTENSION

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 19 (5.26%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VENOUS THROMBOSIS

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

DISEASE PROGRESSION

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

FATIGUE

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

ENDOMETRIAL HYPERPLASIA

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

DYSPNOEA

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

PLEURAL EFFUSION

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

PULMONARY EMBOLISM

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

1 / 6 (16.67%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMOTHORAX

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Product issues

DEVICE DISLOCATION

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

BLOOD BILIRUBIN INCREASED

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Injury, poisoning and procedural complications

FALL

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FRACTURE

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HIP FRACTURE

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

ATRIAL FIBRILLATION

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

CARDIAC ARREST

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CARDIAC FAILURE

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Nervous system disorders

HEADACHE

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SEIZURE

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SYNCOPE

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

ANAEMIA

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

THROMBOCYTOPENIA

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

DIARRHOEA

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ABDOMINAL PAIN

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ASCITES

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 19 (5.26%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

NAUSEA

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VOMITING

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

2 / 19 (10.53%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

HEPATIC HAEMORRHAGE

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 19 (5.26%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

ACUTE KIDNEY INJURY

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

HYDRONEPHROSIS

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

ADRENAL INSUFFICIENCY

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

PAIN IN EXTREMITY

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

APPENDICITIS PERFORATED

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SEPSIS

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

1 / 19 (5.26%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMONIA

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 19 (0.00%)

1 / 10 (10.00%)

0 / 19 (0.00%)

2 / 53 (3.77%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

SKIN INFECTION

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

URINARY TRACT INFECTION

alternative assessment type: Systematic

subjects affected / exposed

1 / 3 (33.33%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 19 (5.26%)

0 / 10 (0.00%)

0 / 19 (0.00%)

0 / 53 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

HYPONATRAEMIA

alternative assessment type: Systematic

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 19 (0.00%)

0 / 10 (0.00%)

0 / 19 (0.00%)

1 / 53 (1.89%)

0 / 6 (0.00%)

0 / 4 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Phase Ia – Cohort 1	Phase Ia - Cohort 2	Phase Ia – Cohort 6	Phase Ia – Cohort 3	Phase Ia – Cohort 9	Phase Ia – Cohort 5	Phase Ia – Cohort 4	Phase Ia – Cohort 8	Phase Ia – Cohort 7	Phase IIa – Cohort A1	Phase IIa – Cohort A2	Phase IIa – Cohort B2	Phase IIa – Cohort B1	Phase Ib – Cohort D1	Phase Ib – Cohort C1
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	4 / 4 (100.00%)	6 / 6 (100.00%)	4 / 4 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	18 / 19 (94.74%)	10 / 10 (100.00%)	19 / 19 (100.00%)	51 / 53 (96.23%)	6 / 6 (100.00%)	4 / 4 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
SQUAMOUS CELL CARCINOMA OF SKIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Vascular disorders
DEEP VEIN THROMBOSIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	2	0	1
FLUSHING
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	1	0	0	1	0
HAEMATOMA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0
HOT FLUSH
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	3 / 6 (50.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 3 (0.00%)	2 / 6 (33.33%)	7 / 19 (36.84%)	0 / 10 (0.00%)	9 / 19 (47.37%)	10 / 53 (18.87%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	1	6	0	0	1	2	0	2	7	0	9	11	0	1
HYPERTENSION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	1 / 10 (10.00%)	1 / 19 (5.26%)	2 / 53 (3.77%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	1	1	0	0	5	0	0	1	0	1	1	2	0	1
PALLOR
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
LYMPHOEDEMA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
ASTHENIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	4 / 53 (7.55%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	4	1	0
CHEST DISCOMFORT
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0
CHEST PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	1	0	2
CHILLS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	3 / 4 (75.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	1 / 10 (10.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	2 / 6 (33.33%)	0 / 4 (0.00%)
occurrences all number	0	1	0	3	0	0	1	0	0	1	1	0	2	2	0
FATIGUE
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	2 / 6 (33.33%)	3 / 4 (75.00%)	3 / 3 (100.00%)	5 / 6 (83.33%)	5 / 6 (83.33%)	2 / 3 (66.67%)	6 / 6 (100.00%)	8 / 19 (42.11%)	2 / 10 (20.00%)	7 / 19 (36.84%)	27 / 53 (50.94%)	3 / 6 (50.00%)	2 / 4 (50.00%)
occurrences all number	2	2	2	3	7	6	7	3	12	9	3	7	29	3	2
GAIT DISTURBANCE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0
IMPAIRED HEALING
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
MALAISE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
MUCOSAL INFLAMMATION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	1	0	0	0	0
OEDEMA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
OEDEMA PERIPHERAL
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	3 / 6 (50.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	1 / 19 (5.26%)	3 / 53 (5.66%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	3	1	0	0	0	1	1	3	0	0
PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	2	0	0
PYREXIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	2 / 4 (50.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	4 / 53 (7.55%)	2 / 6 (33.33%)	0 / 4 (0.00%)
occurrences all number	0	2	2	0	0	0	0	1	2	0	0	1	4	2	0
SWELLING
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0
SWELLING FACE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0
TENDERNESS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
FACIAL PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Reproductive system and breast disorders
BREAST ATROPHY
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
BREAST PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	1	1	0	0	0
ENDOMETRIAL THICKENING
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	1	0	2	0	0	0	0	0	0	0	0	0	1	1	0
OEDEMA GENITAL
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
PELVIC PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1	1	0
UTERINE POLYP
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	0	1	0	0
VAGINAL DISCHARGE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 3 (33.33%)	0 / 6 (0.00%)	9 / 19 (47.37%)	0 / 10 (0.00%)	4 / 19 (21.05%)	8 / 53 (15.09%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	2	1	1	1	0	9	0	4	9	1	0
VAGINAL HAEMORRHAGE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	2	0	0
VULVOVAGINAL DRYNESS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0
DYSPAREUNIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
ASTHMA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0
COUGH
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	2 / 6 (33.33%)	2 / 4 (50.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	2 / 3 (66.67%)	2 / 6 (33.33%)	2 / 19 (10.53%)	1 / 10 (10.00%)	5 / 19 (26.32%)	8 / 53 (15.09%)	1 / 6 (16.67%)	1 / 4 (25.00%)
occurrences all number	1	1	2	3	0	1	2	2	2	2	1	6	11	1	4
DRY THROAT
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
DYSPNOEA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	2 / 6 (33.33%)	3 / 19 (15.79%)	2 / 10 (20.00%)	2 / 19 (10.53%)	5 / 53 (9.43%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	0	1	1	2	3	2	2	5	0	1
DYSPNOEA EXERTIONAL
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	1	1	0	0	0	0
HAEMOPTYSIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
NASAL CONGESTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	2	2	0	0	0	0	0	0	0	0	1	1	0
OROPHARYNGEAL PAIN
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0	1	0	1	0	0
PRODUCTIVE COUGH
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	0	0	1	0	0	0
PULMONARY EMBOLISM
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1	0	0	0	1
RHINORRHOEA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	2	0	0
UPPER-AIRWAY COUGH SYNDROME
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	1	0	0
WHEEZING
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	1
EPISTAXIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
HYPOXIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
PLEURAL EFFUSION
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Psychiatric disorders
ANXIETY
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	1 / 10 (10.00%)	0 / 19 (0.00%)	3 / 53 (5.66%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	1	1	0	0	1	1	0	3	0	0
DEPRESSION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 19 (5.26%)	2 / 10 (20.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	1	1	2	0	2	0	0
INSOMNIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 19 (10.53%)	0 / 10 (0.00%)	1 / 19 (5.26%)	5 / 53 (9.43%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	1	5	1	0
MOOD SWINGS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
SUICIDAL IDEATION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
IRRITABILITY
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	1	0	0	0	1	0	0	0	0	0	0	0
MOOD ALTERED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED
alternative assessment type: Systematic
subjects affected / exposed	2 / 3 (66.67%)	1 / 4 (25.00%)	3 / 6 (50.00%)	0 / 4 (0.00%)	2 / 3 (66.67%)	3 / 6 (50.00%)	3 / 6 (50.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	2 / 10 (20.00%)	0 / 19 (0.00%)	5 / 53 (9.43%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	2	1	4	0	3	5	8	0	0	1	2	0	6	0	1
ASPARTATE AMINOTRANSFERASE INCREASED
alternative assessment type: Systematic
subjects affected / exposed	2 / 3 (66.67%)	1 / 4 (25.00%)	4 / 6 (66.67%)	0 / 4 (0.00%)	2 / 3 (66.67%)	3 / 6 (50.00%)	4 / 6 (66.67%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 19 (5.26%)	2 / 10 (20.00%)	1 / 19 (5.26%)	4 / 53 (7.55%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	2	1	7	0	3	4	6	0	1	1	2	1	5	0	1
BLOOD ALKALINE PHOSPHATASE INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	3 / 6 (50.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	1 / 10 (10.00%)	1 / 19 (5.26%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	2	0	1	0	4	0	2	0	1	1	3	0	0
BLOOD BILIRUBIN INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	4	0	0
BLOOD CREATININE INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0
BLOOD LACTATE DEHYDROGENASE INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	3 / 6 (50.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	4	0	1	1	2	0	0	0	0	0	2	0	0
BLOOD PHOSPHORUS INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0
BLOOD URIC ACID INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
HAEMOGLOBIN DECREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	1	0	1	0
LIVER FUNCTION TEST INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
NEUTROPHIL COUNT DECREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	1	5	0	0	0	0	0	1	0	0
TRANSAMINASES INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	3 / 53 (5.66%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0
WEIGHT DECREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	1 / 10 (10.00%)	0 / 19 (0.00%)	3 / 53 (5.66%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	4	2	0	0	1	1	0	3	0	0
WEIGHT INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	0	1
WHITE BLOOD CELL COUNT DECREASED
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	1	1	3	0	3	10	1	0	0	1	0	1	0	1
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
AMYLASE INCREASED
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
BILIRUBIN CONJUGATED INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
BLOOD ALKALINE PHOSPHATASE DECREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
BLOOD CHLORIDE DECREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
BLOOD CHOLESTEROL INCREASED
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	4 / 6 (66.67%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	6	1	0	0	2	1	0	0	0	0	0	0	0
BLOOD THYROID STIMULATING HORMONE INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
BLOOD URINE PRESENT
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
CRYSTAL URINE PRESENT
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0	0	1	0	0	0	0	0	0	0	0
GLUCOSE URINE PRESENT
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
HIGH DENSITY LIPOPROTEIN DECREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
HIGH DENSITY LIPOPROTEIN INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0	0	2	1	0	0	0	0	0	0	0
LOW DENSITY LIPOPROTEIN INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	3 / 6 (50.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	5	1	1	0	3	0	0	0	0	0	0	0	0
LYMPHOCYTE COUNT DECREASED
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	4	0	0	2	0	0	0	0	0	0	0	0
NEUTROPHIL COUNT INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
NITRITE URINE PRESENT
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
PLATELET COUNT DECREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
RED BLOOD CELL COUNT DECREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	1	0	1	0	0	0	0	0	0	0	0
RED BLOOD CELLS URINE POSITIVE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
URINARY CASTS PRESENT
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0
WHITE BLOOD CELL COUNT INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
CONTUSION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	3 / 53 (5.66%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	2	0	4	0	0
FALL
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
HAND FRACTURE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0
PELVIC FRACTURE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
PROCEDURAL PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	2	0	0
ARTHROPOD BITE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
MUSCLE STRAIN
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
RIB FRACTURE
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0
SKIN LACERATION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
SPINAL FRACTURE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
WOUND
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Cardiac disorders
ANGINA PECTORIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
BRADYCARDIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
PALPITATIONS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	4	0	0	0	0	0	1	0	0	0	0	0
SINUS TACHYCARDIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	0	0	0	1	0	1
PERICARDIAL EFFUSION
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
SINUS BRADYCARDIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Nervous system disorders
ATAXIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
DIZZINESS
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 19 (5.26%)	1 / 10 (10.00%)	2 / 19 (10.53%)	2 / 53 (3.77%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	1	0	0	1	1	1	1	2	0	1	2	2	2	1	0
DYSGEUSIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	4 / 53 (7.55%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	1	0	2	0	0	1	0	0	4	0	0
HEADACHE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	1 / 19 (5.26%)	9 / 53 (16.98%)	2 / 6 (33.33%)	1 / 4 (25.00%)
occurrences all number	0	1	1	1	0	1	3	0	0	1	0	1	12	3	1
HYPERSOMNIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
MEMORY IMPAIRMENT
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
MIGRAINE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0
NEUROPATHY PERIPHERAL
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	1	0	1	0	0
PARAESTHESIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	3 / 53 (5.66%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	6	1	0
PERIPHERAL SENSORY NEUROPATHY
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	3 / 53 (5.66%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	3	0	1
SCIATICA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0
TASTE DISORDER
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	2	1	0	0	0	0	0
VOCAL CORD PARALYSIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
LETHARGY
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Blood and lymphatic system disorders
ANAEMIA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	2 / 4 (50.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	2 / 3 (66.67%)	4 / 6 (66.67%)	3 / 6 (50.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	2 / 19 (10.53%)	2 / 10 (20.00%)	4 / 19 (21.05%)	6 / 53 (11.32%)	0 / 6 (0.00%)	2 / 4 (50.00%)
occurrences all number	1	2	2	3	3	13	3	1	3	2	2	8	6	0	2
LYMPHOPENIA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	1	0	0	3	0	0	1	1	0	0
NEUTROPENIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	3 / 4 (75.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	1	0	1	0	5
THROMBOCYTOPENIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	2 / 10 (20.00%)	0 / 19 (0.00%)	3 / 53 (5.66%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	4	0	3	0	1
Ear and labyrinth disorders
EAR PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
EXTERNAL EAR PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
TINNITUS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0
Eye disorders
BLEPHARITIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
DRY EYE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	1 / 6 (16.67%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	1	0	0	1	1	1
EYELID PTOSIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
VISION BLURRED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	2	0	0	0	0	0
IDIOPATHIC ORBITAL INFLAMMATION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
LACRIMATION INCREASED
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
PHOTOPSIA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
ABDOMINAL DISCOMFORT
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	2 / 53 (3.77%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	1	2	1	0
ABDOMINAL DISTENSION
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 19 (10.53%)	1 / 10 (10.00%)	1 / 19 (5.26%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	1	3	0	0	2	0	1	2	1	1	2	0	0
ABDOMINAL PAIN
alternative assessment type: Systematic
subjects affected / exposed	2 / 3 (66.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	3 / 4 (75.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	3 / 19 (15.79%)	0 / 10 (0.00%)	1 / 19 (5.26%)	10 / 53 (18.87%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	2	0	1	3	1	1	3	0	1	3	0	3	11	1	0
ABDOMINAL PAIN LOWER
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	0	0	1	0	0
ABDOMINAL PAIN UPPER
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 19 (10.53%)	1 / 10 (10.00%)	0 / 19 (0.00%)	6 / 53 (11.32%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	1	0	11	0	0
COLITIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0
CONSTIPATION
alternative assessment type: Systematic
subjects affected / exposed	2 / 3 (66.67%)	0 / 4 (0.00%)	2 / 6 (33.33%)	3 / 4 (75.00%)	2 / 3 (66.67%)	2 / 6 (33.33%)	4 / 6 (66.67%)	0 / 3 (0.00%)	2 / 6 (33.33%)	2 / 19 (10.53%)	0 / 10 (0.00%)	4 / 19 (21.05%)	16 / 53 (30.19%)	3 / 6 (50.00%)	0 / 4 (0.00%)
occurrences all number	2	0	2	3	2	2	7	0	5	2	0	4	21	3	0
DIARRHOEA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	4 / 6 (66.67%)	4 / 4 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	4 / 6 (66.67%)	3 / 3 (100.00%)	6 / 6 (100.00%)	10 / 19 (52.63%)	5 / 10 (50.00%)	11 / 19 (57.89%)	28 / 53 (52.83%)	6 / 6 (100.00%)	2 / 4 (50.00%)
occurrences all number	1	2	12	11	6	22	6	7	21	16	11	30	66	13	2
DRY MOUTH
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	3 / 6 (50.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 3 (0.00%)	2 / 6 (33.33%)	5 / 19 (26.32%)	0 / 10 (0.00%)	2 / 19 (10.53%)	6 / 53 (11.32%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	3	1	0	1	2	0	2	5	0	2	8	0	0
DYSPEPSIA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	2 / 6 (33.33%)	1 / 3 (33.33%)	2 / 6 (33.33%)	6 / 19 (31.58%)	2 / 10 (20.00%)	2 / 19 (10.53%)	6 / 53 (11.32%)	3 / 6 (50.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	1	1	2	2	2	2	6	2	2	6	3	0
DYSPHAGIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	3 / 53 (5.66%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	3	0	0
ERUCTATION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	2	0	0
FLATULENCE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	5 / 6 (83.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	1 / 3 (33.33%)	1 / 6 (16.67%)	4 / 19 (21.05%)	0 / 10 (0.00%)	0 / 19 (0.00%)	13 / 53 (24.53%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	6	0	0	2	3	1	1	4	0	0	14	1	0
GASTROINTESTINAL HAEMORRHAGE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
GASTROOESOPHAGEAL REFLUX DISEASE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	5 / 6 (83.33%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 19 (10.53%)	0 / 10 (0.00%)	3 / 19 (15.79%)	9 / 53 (16.98%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	5	0	2	0	1	0	0	2	0	5	10	0	1
HAEMORRHOIDAL HAEMORRHAGE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0
HAEMORRHOIDS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0
NAUSEA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	3 / 4 (75.00%)	4 / 6 (66.67%)	2 / 4 (50.00%)	2 / 3 (66.67%)	2 / 6 (33.33%)	6 / 6 (100.00%)	2 / 3 (66.67%)	6 / 6 (100.00%)	8 / 19 (42.11%)	6 / 10 (60.00%)	9 / 19 (47.37%)	24 / 53 (45.28%)	4 / 6 (66.67%)	3 / 4 (75.00%)
occurrences all number	1	4	4	4	7	3	11	2	15	9	6	10	32	8	6
PANCREATITIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0
STOMATITIS
alternative assessment type: Systematic
subjects affected / exposed	2 / 3 (66.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	2	0	2	1	1	0	1	0	0	0	0	0	1	0	1
VOMITING
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	2 / 4 (50.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	2 / 3 (66.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	3 / 3 (100.00%)	4 / 6 (66.67%)	7 / 19 (36.84%)	4 / 10 (40.00%)	2 / 19 (10.53%)	14 / 53 (26.42%)	3 / 6 (50.00%)	0 / 4 (0.00%)
occurrences all number	1	3	3	1	4	3	2	5	15	11	5	2	22	5	0
ASCITES
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
FAECES SOFT
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
GASTROINTESTINAL INFLAMMATION
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
GINGIVAL PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
GINGIVAL SWELLING
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
LIP SWELLING
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
ORAL MUCOSAL ERUPTION
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
SMALL INTESTINAL OBSTRUCTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
ACNE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0
ALOPECIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 19 (10.53%)	1 / 10 (10.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	2	0	0	2	1	0	2	0	0
BLISTER
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
DERMATITIS ACNEIFORM
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	0	0	0	0	0	0	3	0	0	0	0	0	0	1
DRY SKIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	2 / 53 (3.77%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0	1	2	1	0
ERYTHEMA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	0	0	1	0	1
HYPERHIDROSIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
PAPULE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
PRURITUS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	2 / 53 (3.77%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	1	3	1	0
RASH
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	2 / 10 (20.00%)	2 / 19 (10.53%)	3 / 53 (5.66%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	2	2	3	0	1
RASH MACULO-PAPULAR
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	1	0	0	0	0	1	0	0	2	1	0
SKIN ULCER
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
URTICARIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0
ERYTHEMA MULTIFORME
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
LICHEN SCLEROSUS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
MACULE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
MADAROSIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
PAIN OF SKIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
RASH ERYTHEMATOUS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Renal and urinary disorders
ACUTE KIDNEY INJURY
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
DYSURIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	1	2	0	0
HAEMATURIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	4 / 53 (7.55%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	2	0	0	0	0	0	0	0	0	4	0	0
MICTURITION URGENCY
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 19 (10.53%)	0 / 10 (0.00%)	0 / 19 (0.00%)	4 / 53 (7.55%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	1	0	0	0	0	2	0	0	4	0	0
URINARY RETENTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0
URINARY TRACT PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	1 / 19 (5.26%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	1	0	0
PROTEINURIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0
RENAL DISORDER
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
URINARY TRACT DISORDER
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	3 / 6 (50.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	4 / 6 (66.67%)	2 / 6 (33.33%)	1 / 3 (33.33%)	0 / 6 (0.00%)	4 / 19 (21.05%)	0 / 10 (0.00%)	0 / 19 (0.00%)	14 / 53 (26.42%)	1 / 6 (16.67%)	1 / 4 (25.00%)
occurrences all number	1	0	3	1	3	5	2	1	0	5	0	0	18	2	1
BACK PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	3 / 6 (50.00%)	2 / 4 (50.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 6 (16.67%)	4 / 19 (21.05%)	0 / 10 (0.00%)	4 / 19 (21.05%)	13 / 53 (24.53%)	1 / 6 (16.67%)	2 / 4 (50.00%)
occurrences all number	0	1	4	2	1	1	1	0	1	4	0	4	15	1	2
BONE PAIN
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	3 / 53 (5.66%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	3	1	0
FLANK PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
MUSCLE SPASMS
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	2 / 4 (50.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	2 / 6 (33.33%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 19 (5.26%)	1 / 10 (10.00%)	1 / 19 (5.26%)	4 / 53 (7.55%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	2	4	0	1	1	3	1	1	1	1	1	5	0	0
MUSCULAR WEAKNESS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 19 (10.53%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	2	0	0	1	0	0
MUSCULOSKELETAL CHEST PAIN
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	5 / 53 (9.43%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	1	0	1	2	0	0	0	1	0	1	0	5	0	2
MUSCULOSKELETAL PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	1 / 19 (5.26%)	7 / 53 (13.21%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	1	1	7	0	1
MUSCULOSKELETAL STIFFNESS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
MYALGIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 19 (10.53%)	1 / 10 (10.00%)	2 / 19 (10.53%)	3 / 53 (5.66%)	2 / 6 (33.33%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	1	0	4	0	0	2	1	2	5	2	0
NECK MASS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
NECK PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	1 / 10 (10.00%)	0 / 19 (0.00%)	3 / 53 (5.66%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	3	0	1	0	3	0	0	1	1	0	3	0	0
OSTEONECROSIS OF JAW
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0
PAIN IN EXTREMITY
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	2 / 3 (66.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	4 / 19 (21.05%)	1 / 10 (10.00%)	1 / 19 (5.26%)	4 / 53 (7.55%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	2	2	1	0	0	4	1	1	6	0	0
PAIN IN JAW
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
SPINAL PAIN
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
GROIN PAIN
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	1	1	0	0	0	0	0	0	0	0	0	0
JOINT STIFFNESS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Infections and infestations
CELLULITIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1	0	1
DIVERTICULITIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0
EYE INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	2	0	0
HERPES ZOSTER
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
LOCALISED INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
NASOPHARYNGITIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0
ORAL HERPES
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
PNEUMONIA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	0	0	0	0	1	0	0	1	1	0	0	0	0	1
SINUSITIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	3 / 19 (15.79%)	3 / 53 (5.66%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	3	3	0	0
SKIN INFECTION
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1
STAPHYLOCOCCAL INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
TOOTH INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
UPPER RESPIRATORY TRACT INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	1 / 6 (16.67%)	1 / 4 (25.00%)
occurrences all number	0	0	0	1	0	3	1	0	0	1	0	0	1	1	1
URINARY TRACT INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	0 / 10 (0.00%)	2 / 19 (10.53%)	8 / 53 (15.09%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0	0	2	9	0	1
VAGINAL INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 19 (5.26%)	0 / 10 (0.00%)	1 / 19 (5.26%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	2	1	0	0
VIRAL INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
VULVOVAGINAL MYCOTIC INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1
BREAST CELLULITIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
BRONCHITIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
CROUP INFECTIOUS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
FUNGAL INFECTION
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
FURUNCLE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
GASTROENTERITIS NOROVIRUS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
GASTROENTERITIS VIRAL
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
GINGIVITIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
HELICOBACTER INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
INFLUENZA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
ORAL CANDIDIASIS
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
OTITIS EXTERNA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
VIRAL UPPER RESPIRATORY TRACT INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
WOUND INFECTION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
DECREASED APPETITE
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	2 / 3 (66.67%)	2 / 6 (33.33%)	3 / 6 (50.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	6 / 19 (31.58%)	3 / 10 (30.00%)	2 / 19 (10.53%)	9 / 53 (16.98%)	4 / 6 (66.67%)	1 / 4 (25.00%)
occurrences all number	0	1	1	2	6	2	4	0	2	6	3	2	9	4	1
DEHYDRATION
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	1 / 53 (1.89%)	1 / 6 (16.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	1	0	0	1	1	1	0
HYPERGLYCAEMIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	2 / 6 (33.33%)	2 / 4 (50.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 19 (5.26%)	1 / 10 (10.00%)	2 / 19 (10.53%)	3 / 53 (5.66%)	0 / 6 (0.00%)	2 / 4 (50.00%)
occurrences all number	0	1	3	2	2	3	0	0	2	1	1	2	4	0	2
HYPERKALAEMIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	2 / 53 (3.77%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	1	2	0	0	0	0	0	0	0	2	0	0
HYPERTRIGLYCERIDAEMIA
alternative assessment type: Systematic
subjects affected / exposed	2 / 3 (66.67%)	1 / 4 (25.00%)	3 / 6 (50.00%)	1 / 4 (25.00%)	2 / 3 (66.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	3 / 53 (5.66%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	3	1	5	1	2	1	0	0	0	0	0	0	3	0	0
HYPERURICAEMIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	3 / 6 (50.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	6	0	0	1	4	0	0	0	0	0	1	0	0
HYPOALBUMINAEMIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0
HYPOCALCAEMIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	1 / 19 (5.26%)	1 / 53 (1.89%)	0 / 6 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	1	1	1	0	0	0	0	0	0	0	1	1	0	1
HYPOGLYCAEMIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	0	0	1	0	0
HYPOMAGNESAEMIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	3	0	1	0	0	2	0	0	0	0
HYPONATRAEMIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 19 (0.00%)	1 / 10 (10.00%)	0 / 19 (0.00%)	1 / 53 (1.89%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	3	4	1	1	0	1	0	1	0	0
HYPOPHOSPHATAEMIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	3 / 6 (50.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	2 / 10 (20.00%)	2 / 19 (10.53%)	2 / 53 (3.77%)	1 / 6 (16.67%)	2 / 4 (50.00%)
occurrences all number	0	2	0	0	0	3	0	0	1	0	3	2	2	1	2
HYPERCALCAEMIA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	1	1	0	0	0	0	0	0	0	0
HYPERMAGNESAEMIA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	3	1	0	0	0	0	0	0	1	0	0	0	0	0	0
HYPERPROTEINAEMIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
HYPOCHLORAEMIA
alternative assessment type: Systematic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
HYPOKALAEMIA
alternative assessment type: Systematic
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 19 (0.00%)	0 / 10 (0.00%)	0 / 19 (0.00%)	0 / 53 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	3	0	0	0	0	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

23 Apr 2013

Protocol was amended with changes to the inclusion/exclusion criteria, clinical laboratory assessments, and PK assessments.

11 Oct 2013

Protocol was amended to include changes to the sponsor name (Aragon Pharm was changed to Seragon), add exploratory objectives, dose escalation PK and ECG sample collection, and drug access if receiving clinical benefit.

20 Jun 2014

Protocol was amended to update the inclusion/exclusion criteria, study rationale, name of the dose expansion phase to Phase IIa, dosing regimen, and Phase IIa objectives.

02 Jan 2015

Protocol was amended to update as the per transfer of IND ownership of GDC-0810 to Genentech Inc.

18 Dec 2015

Protocol was amended to include Phase Ib combination cohorts with palbociclib and luteinizing hormone releasing hormone (LHRH) agonists

25 Jan 2017

Protocol was amended to reduce the number of required study procedures as a result of Sponsor decision to halt the development of GDC-0810 and halt enrollment into the study.

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: An Open-Label, Phase Ia/Ib/IIa Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or an LHRH Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent

Primary: Phase Ia: Maximum Tolerated Dose of GDC-0810 When Used as a Single Agent

Primary: Phase Ia: Recommended Phase II Dose (RP2D) of GDC-0810 When Used as a Single Agent

Primary: Phase Ia: Recommended Phase II Dose (RP2D) of GDC-0810 When Used as a Single Agent

Primary: Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1

Primary: Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1

Primary: Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Primary: Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Primary: Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH

Primary: Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH

Secondary: All Phases: Percentage of Participants With Adverse Events (AEs)

Secondary: All Phases: Percentage of Participants With Adverse Events (AEs)

Secondary: Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Secondary: Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Secondary: Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Secondary: Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Secondary: Phase Ia: Area Under the Concentration-time Curves at 6 hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Secondary: Phase Ia: Area Under the Concentration-time Curves at 6 hours (AUC0-6) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Secondary: Phase Ia: Area Under the Concentration-time Curves at 24 hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Secondary: Phase Ia: Area Under the Concentration-time Curves at 24 hours (AUC0-24) of GDC-0810 Single Agent and Its Glucuronide Metabolites

Secondary: Area under the concentration–time curve from Time 0 to infinity (AUC0-Inf)

Secondary: Area under the concentration–time curve from Time 0 to infinity (AUC0-Inf)

Secondary: Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent

Secondary: Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent

Secondary: Phase Ia: Apparent Clearance (Cl/F)

Secondary: Phase Ia: Apparent Clearance (Cl/F)

Secondary: Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula

Secondary: Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula

Secondary: Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Secondary: Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Secondary: Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Secondary: Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Secondary: Phase Ib: AUC of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Secondary: Phase Ib: AUC of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Secondary: Phase Ib: t/2 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Secondary: Phase Ib: t/2 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist

Secondary: Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Secondary: Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Secondary: Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Secondary: Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Secondary: Phase Ib: AUC of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Secondary: Phase Ib: AUC of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Secondary: Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Secondary: Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist

Secondary: Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Secondary: Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Secondary: Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Secondary: Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Secondary: Phase Ib: AUC of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib

Secondary: Phase Ib: AUC of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib

Secondary: Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Secondary: Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
An Open-Label, Phase Ia/Ib/IIa Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or an LHRH Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer