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Clinical Trial Results:
A Double-Blind, Efficacy and Safety Study of Duloxetine Versus Placebo in the Treatment of Children and Adolescents With Major Depressive Disorder

Summary
EudraCT number	2017-001598-18
Trial protocol	Outside EU/EEA
Global end of trial date	05 Sep 2011

Results information
Results version number	v1(current)
This version publication date	22 Dec 2021
First version publication date	22 Dec 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

F1J‐MC‐HMCL

ISRCTN number

US NCT number

NCT00849693

WHO universal trial number (UTN)

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

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

Public contact

Available Mon-Fri 9 AM - 5 PM EST, Eli Lilly and Company Limited, 1 877-CTLilly, EU_Lilly_Clinical_Trials@lilly.com

Scientific contact

Available Mon-Fri 9 AM - 5 PM EST, Eli Lilly and Company Limited, 1 877-285-4559, EU_Lilly_Clinical_Trials@lilly.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?

Yes

Analysis stage

Final

Date of interim/final analysis

05 Sep 2011

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Sep 2011

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to assess whether duloxetine is superior to placebo in the treatment of children and adolescents with major depressive disorder (MDD).

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

16 Mar 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 364

Country: Number of subjects enrolled

Mexico: 74

Country: Number of subjects enrolled

Canada: 24

Country: Number of subjects enrolled

Argentina: 1

Worldwide total number of subjects

463

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)

463

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study consisted of a 10-week acute treatment phase, and a 6-month extension phase.

Screening details

Not Applicable

Period 1 title

Acute Treatment Phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Duloxetine 60 mg

Arm description

Participants were treated with Duloxetine 60 milligram (mg) orally, once daily for 10 weeks during acute treatment phase.

Arm type

Experimental

Investigational medicinal product name

Duloxetine

Investigational medicinal product code

Other name

LY248686, Cymbalta

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Duloxetine 60 mg, orally, once daily for 10 weeks.

Duloxetine 30 mg

Arm description

Duloxetine 30 mg, orally, once daily for 10 weeks.

Arm type

Experimental

Investigational medicinal product name

Duloxetine

Investigational medicinal product code

Other name

LY248686, Cymbalta

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Duloxetine 30 mg, orally, once daily for 10 weeks.

Fluoxetine 20 mg

Arm description

Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks during acute treatment phase.

Arm type

Experimental

Investigational medicinal product name

Fluoxetine

Investigational medicinal product code

Other name

LY110140; Prozac

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks.

Placebo

Arm description

Participants were treated with placebo orally, once daily for 10 weeks during acute treatment phase.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants were treated with placebo orally, once daily for 10 weeks.

Number of subjects in period 1	Duloxetine 60 mg	Duloxetine 30 mg	Fluoxetine 20 mg	Placebo
Started	108	116	117	122
Completed	75	81	84	85
Not completed	33	35	33	37
Consent withdrawn by subject	5	5	3	8
Physician decision	2	1	2	1
Adverse event, non-fatal	12	7	6	4
Sponsor Decision	-	-	1	-
Lost to follow-up	5	8	11	9
Parent or caregiver decision	7	6	7	7
Protocol deviation	1	5	2	6
Lack of efficacy	1	3	1	2

Period 2 title

Extension Phase

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Duloxetine 60-120 mg

Arm description

Participants received Duloxetine 60-120 mg orally, once daily for 6 months during extension phase.

Arm type

Experimental

Investigational medicinal product name

Duloxetine

Investigational medicinal product code

Other name

LY248686, Cymbalta

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Duloxetine 60-120 mg orally, once daily for 6 months.

Duloxetine 60-120 mg

Arm description

Participants received Duloxetine 60-120 mg orally, once daily for 6 months during extension phase

Arm type

Experimental

Investigational medicinal product name

Duloxetine

Investigational medicinal product code

Other name

LY248686, Cymbalta

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Duloxetine 60-120 mg orally, once daily for 6 months.

Fluoxetine 20-40 mg

Arm description

Participants received Fluoxetine 20-40 mg orally, once daily for 6 months during extension phase.

Arm type

Experimental

Investigational medicinal product name

Fluoxetine

Investigational medicinal product code

Other name

LY110140; Prozac

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Fluoxetine 20-40 mg orally, once daily for 6 months.

Duloxetine 60-120 mg

Arm description

Participants received Duloxetine 60-120 mg orally, once daily for 6 months during extension phase.

Arm type

Experimental

Investigational medicinal product name

Duloxetine

Investigational medicinal product code

Other name

LY248686, Cymbalta

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Duloxetine 60-120 mg orally, once daily for 6 months.

Number of subjects in period 2 ^[1]	Duloxetine 60-120 mg	Duloxetine 60-120 mg	Fluoxetine 20-40 mg	Duloxetine 60-120 mg
Started	73	80	84	82
Completed	43	50	49	44
Not completed	30	30	35	38
Consent withdrawn by subject	6	9	10	15
Physician decision	1	1	2	-
Adverse event, non-fatal	4	6	3	7
Sponsor Decision	1	-	-	1
Lost to follow-up	7	5	6	6
Parent or caregiver decision	9	4	10	5
Lack of efficacy	2	2	2	1
Protocol deviation	-	3	2	3

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Few participants decided not to enter Extension phase.

Baseline characteristics

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Reporting group title

Duloxetine 60 mg

Reporting group description

Participants were treated with Duloxetine 60 milligram (mg) orally, once daily for 10 weeks during acute treatment phase.

Reporting group title

Duloxetine 30 mg

Reporting group description

Duloxetine 30 mg, orally, once daily for 10 weeks.

Reporting group title

Fluoxetine 20 mg

Reporting group description

Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks during acute treatment phase.

Reporting group title

Placebo

Reporting group description

Participants were treated with placebo orally, once daily for 10 weeks during acute treatment phase.

Reporting group values	Duloxetine 60 mg	Duloxetine 30 mg	Fluoxetine 20 mg	Placebo	Total
Number of subjects	108	116	117	122	463
Age categorical
Units: Subjects
In utero					0
Preterm newborn infants (gestational age < 37 wks)					0
Newborns (0-27 days)					0
Infants and toddlers (28 days-23 months)					0
Children (2-11 years)					0
Adolescents (12-17 years)					0
Adults (18-64 years)					0
From 65-84 years					0
85 years and over					0
Age continuous
Units: years
arithmetic mean (standard deviation)	12.92 ± 2.925	12.86 ± 2.904	13.04 ± 3.205	13.09 ± 2.895	-
Gender categorical
Units: Subjects
Female	60	47	61	69	237
Male	48	69	56	53	226
Race and Ethnicity
Units: Subjects
American Indian or Alaska Native	15	23	16	19	73
Asian	0	1	1	1	3
Black or African American	27	21	21	24	93
Native Hawaiian or Other Pacific Islander	0	1	0	0	1
White	54	61	67	62	244
Multiracial	6	6	9	13	34
Not Provided	6	3	3	3	15
Region of Enrollment
Units: Subjects
United States	87	86	93	98	364
Mexico	16	25	16	17	74
Canada	5	5	7	7	24
Argentina	0	0	1	0	1
Children's Depression Rating Scale-Revised (CDRS-R) Total Score
CDRS-R Total score measure the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression.
Units: Units on a Scale
arithmetic mean (standard deviation)	59.3 ± 10.87	59.8 ± 11.00	57.9 ± 10.11	58.2 ± 9.35	-

End points

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Reporting group title

Duloxetine 60 mg

Reporting group description

Participants were treated with Duloxetine 60 milligram (mg) orally, once daily for 10 weeks during acute treatment phase.

Reporting group title

Duloxetine 30 mg

Reporting group description

Duloxetine 30 mg, orally, once daily for 10 weeks.

Reporting group title

Fluoxetine 20 mg

Reporting group description

Participants were treated with Fluoxetine 20 mg orally, once daily for 10 weeks during acute treatment phase.

Reporting group title

Placebo

Reporting group description

Participants were treated with placebo orally, once daily for 10 weeks during acute treatment phase.

Reporting group title

Duloxetine 60-120 mg

Reporting group description

Participants received Duloxetine 60-120 mg orally, once daily for 6 months during extension phase.

Reporting group title

Duloxetine 60-120 mg

Reporting group description

Participants received Duloxetine 60-120 mg orally, once daily for 6 months during extension phase

Reporting group title

Fluoxetine 20-40 mg

Reporting group description

Participants received Fluoxetine 20-40 mg orally, once daily for 6 months during extension phase.

Reporting group title

Duloxetine 60-120 mg

Reporting group description

Participants received Duloxetine 60-120 mg orally, once daily for 6 months during extension phase.

Primary: Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint

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End point title

Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint ^[1]

End point description

CDRS-R Total score measure the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. Least Square (LS) means are adjusted for baseline, pooled investigator, age category, visit, treatment, treatment*visit, age category*visit and baseline*visit. Analysis Population Description: Participants with both a baseline and at least one post-baseline value.

End point type

Primary

End point timeframe

Baseline, Week 10

Notes
[1] - 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: No inferential statistics planned for this outcome.

End point values	Duloxetine 60 mg	Placebo
Number of subjects analysed	105	117
Units: Units on a Scale
least squares mean (standard error)	-23.9 ± 1.30	-21.6 ± 1.27

CDRS-R

Comparison groups

Duloxetine 60 mg v Placebo

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.193

Method

Mixed models analysis

Confidence interval

Secondary: Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint

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End point title

Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint

End point description

CDRS-R Total score measure the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. LS means are adjusted for baseline, pooled investigator, age category, visit, age category*visit and baseline*visit. APD: Participants with value during treatment phase and at least one post-Week 10 value.

End point type

Secondary

End point timeframe

Week 10, Week 36

End point values	Duloxetine 60-120 mg	Duloxetine 60-120 mg	Fluoxetine 20-40 mg	Duloxetine 60-120 mg
Number of subjects analysed	70	78	80	79
Units: Units on a Scale
least squares mean (standard error)	-7.8 ± 1.04	-7.4 ± 1.23	-10.0 ± 1.17	-9.0 ± 1.84

No statistical analyses for this end point

Secondary: Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint

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End point title

Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint ^[2]

End point description

CDRS-R Total score measure the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. Least Square (LS) means are adjusted for baseline, pooled investigator, age category, visit, treatment, treatment*visit, age category*visit and baseline*visit. APD: Participants with both a baseline and at least one post-baseline value.

End point type

Secondary

End point timeframe

Baseline, Week 10

Notes
[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: No inferential statistics planned for this outcome.

End point values	Duloxetine 30 mg	Fluoxetine 20 mg	Placebo
Number of subjects analysed	114	112	117
Units: units on a scale
least squares mean (standard error)	-24.6 ± 1.29	-22.6 ± 1.27	-21.6 ± 1.27

No statistical analyses for this end point

Secondary: Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint

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End point title

Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint

End point description

CDRS-R Subscale scores include Mood (Sum of items 8, 11, 14, 15), Somatic (Sum of items 4-7, 16, 17), Subjective (Sum of items 9, 10, 12, 13) and Behavior (Sum of items 1-3). Mood and Subjective subscale scores range from 4 to 28; Somatic subscale scores range from 6 to 36; Behavior subscale scores range from 3 to 21. Higher score indicates greater severity of disease. LS means are adjusted for baseline, pooled investigator, age category, visit, treatment, treatment*visit, age category*visit and baseline*visit. APD: Participants with both a baseline and at least one post-baseline values.

End point type

Secondary

End point timeframe

Baseline, Week 10

End point values	Duloxetine 60 mg	Duloxetine 30 mg	Fluoxetine 20 mg	Placebo
Number of subjects analysed	105	114	112	117
Units: units on a scale
least squares mean (standard error)
Mood	-7.1 ± 0.44	-7.2 ± 0.44	-6.6 ± 0.43	-6.4 ± 0.43
Somatic	-7.6 ± 0.48	-7.9 ± 0.48	-7.1 ± 0.47	-6.4 ± 0.47
Subjective	-3.6 ± 0.26	-4.0 ± 0.26	-3.5 ± 0.26	-3.6 ± 0.26
Behavior	-5.8 ± 0.36	-5.6 ± 0.36	-5.6 ± 0.35	-5.4 ± 0.35

No statistical analyses for this end point

Secondary: Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint

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End point title

Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint

End point description

CDRS-R Subscale scores include Mood (Sum of items 8, 11, 14, 15), Somatic (Sum of items 4-7, 16, 17), Subjective (Sum of items 9, 10, 12, 13) and Behavior (Sum of items 1-3). Mood and Subjective subscale scores range from 4 to 28; Somatic subscale scores range from 6 to 36; Behavior subscale scores range from 3 to 21. Higher score indicates greater severity of disease. LS means are adjusted for baseline, pooled investigator, age category, visit, age category*visit and baseline*visit. APD: Participants with value during treatment phase and at least one post-Week 10 value.

End point type

Secondary

End point timeframe

Week 10, Week 36

End point values	Duloxetine 60-120 mg	Duloxetine 60-120 mg	Fluoxetine 20-40 mg	Duloxetine 60-120 mg
Number of subjects analysed	70	78	80	79
Units: units on a scale
least squares mean (standard error)
Mood	-1.9 ± 0.43	-1.9 ± 0.42	-2.4 ± 0.44	-2.3 ± 0.59
Somatic	-2.8 ± 0.41	-2.4 ± 0.52	-4.0 ± 0.47	-3.2 ± 0.66
Subjective	-1.2 ± 0.25	-1.3 ± 0.19	-1.5 ± 0.21	-1.0 ± 0.32
Behavior	-2.1 ± 0.30	-1.8 ± 0.32	-2.7 ± 0.28	-2.4 ± 0.50

No statistical analyses for this end point

Secondary: Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint

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End point title

Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint

End point description

CGI-Severity evaluates the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). LS means are adjusted for baseline, pooled investigator, age category, visit, treatment, treatment*visit, age category*visit and baseline*visit. APD: Participants with both a baseline and at least one post-baseline value.

End point type

Secondary

End point timeframe

Baseline, Week 10

End point values	Duloxetine 60 mg	Duloxetine 30 mg	Fluoxetine 20 mg	Placebo
Number of subjects analysed	105	114	112	117
Units: Units on a Scale
least squares mean (standard error)	-1.5 ± 0.12	-1.5 ± 0.12	-1.4 ± 0.11	-1.4 ± 0.11

No statistical analyses for this end point

Secondary: Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint

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End point title

Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint

End point description

CGI-Severity evaluates the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). LS means are adjusted for baseline, pooled investigator, age category, visit, age category*visit and baseline*visit. APD: Participants with value during treatment phase and at least one post-Week 10 value.

End point type

Secondary

End point timeframe

Week 10, Week 36

End point values	Duloxetine 60-120 mg	Duloxetine 60-120 mg	Fluoxetine 20-40 mg	Duloxetine 60-120 mg
Number of subjects analysed	69	78	81	79
Units: units on a scale
least squares mean (standard error)	-1.1 ± 0.13	-0.9 ± 0.16	-1.3 ± 0.12	-1.0 ± 0.13

No statistical analyses for this end point

Secondary: Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10

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End point title

Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10

End point description

Columbia Suicide Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Treatment Emergent Suicidal Ideation is worsening or new occurrence of events during treatment compared to lead-in baseline (Week -1 to 0). APD: Participants with a baseline and at least one post-baseline C-SSRS suicidal ideation or suicidal behavior score and who are at risk for treatment emergent suicidal ideation or behavior.

End point type

Secondary

End point timeframe

Baseline through Week 10

End point values	Duloxetine 60 mg	Duloxetine 30 mg	Fluoxetine 20 mg	Placebo
Number of subjects analysed	105	115	112	117
Units: Participants
number (not applicable)
Suicidal Ideation	16	11	13	15
Suicidal Behavior	0	0	1	1
Treatment Emergent Suicidal Ideation	7	6	9	11

No statistical analyses for this end point

Secondary: Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36

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End point title

Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36

End point description

Columbia Suicide Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Treatment Emergent Suicidal Ideation is worsening or new occurrence of events during treatment compared to lead-in baseline (Week 7-10). APD: Participants with a baseline and at least one post-baseline C-SSRS suicidal ideation or suicidal behavior score and who are at risk for treatment emergent suicidal ideation or behavior.

End point type

Secondary

End point timeframe

Week 10 through Week 36

End point values	Duloxetine 60-120 mg	Duloxetine 60-120 mg	Fluoxetine 20-40 mg	Duloxetine 60-120 mg
Number of subjects analysed	71	78	80	79
Units: Participants
number (not applicable)
Suicidal Ideation	6	12	8	8
Suicidal Behavior	2	3	0	1
Treatment Emergent Suicidal Ideation	5	8	7	6

No statistical analyses for this end point

Secondary: Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10

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End point title

Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10

End point description

Total number of participants with any abnormal post-baseline value, based on all values at scheduled and unscheduled visits. Potentially clinically significant hepatic laboratory results at any time are defined as alanine transaminase (ALT) ≥3 x upper limit of normal (ULN), ALT ≥5 x ULN and ALT ≥10 x ULN, as well as ALT ≥3 x ULN and Total Bilirubin ≥2 x ULN. APD: Participants with normal ALT value (ALT<1 x ULN) at last non-missing baseline visit and at least one non-missing post-baseline value.

End point type

Secondary

End point timeframe

Baseline through Week 10

End point values	Duloxetine 60 mg	Duloxetine 30 mg	Fluoxetine 20 mg	Placebo
Number of subjects analysed	95	98	102	100
Units: Participants
number (not applicable)
ALT≥3 x ULN	0	0	0	0
ALT≥5 x ULN	0	0	0	0
ALT≥10 x ULN	0	0	0	0
ALT≥3 x ULN and Total Bilirubin≥2 x ULN	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36

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End point title

Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36

End point description

End point type

Secondary

End point timeframe

Week 10 through Week 36

End point values	Duloxetine 60-120 mg	Duloxetine 60-120 mg	Fluoxetine 20-40 mg	Duloxetine 60-120 mg
Number of subjects analysed	69	69	77	73
Units: Participants
number (not applicable)
ALT≥3 x ULN	0	0	0	0
ALT≥5 x ULN	0	0	0	0
ALT≥10 x ULN	0	0	0	0
ALT≥3 x ULN and Total Bilirubin≥2 x ULN	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Baseline Through Week 10

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End point title

Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Baseline Through Week 10

End point description

PCS increase in systolic and diastolic BP was defined as increase of ≥5 millimeter mercury (mm Hg) from baseline (BL) high value to a value above the 95th percentile at post-BL; PCS increase of pulse was defined as >140 and increase of ≥15 from BL high value for age 7-11 and >120 and increase of ≥15 from BL high value for age 12-17; PCS decrease of pulse was defined as <60 and a decrease of ≥25 from BL low value for age 7-11 and <50 and a decrease of ≥15 from BL low value for age 12-17; PCS decrease of weight was defined as decrease of at least 3.5% from BL low value. APD: Participants with normal baseline value and at least one post-baseline value, and who were at risk for the specific PCS criteria.

End point type

Secondary

End point timeframe

Baseline through Week 10

End point values	Duloxetine 60 mg	Duloxetine 30 mg	Fluoxetine 20 mg	Placebo
Number of subjects analysed	108 ^[3]	116 ^[4]	117 ^[5]	122 ^[6]
Units: percentage of participants
number (not applicable)
Diastolic BP Increase	11.8	7.0	10.1	4.5
Systolic BP Increase	9.1	12.6	12.9	10.2
Pulse Decrease	0	0	0	0
Pulse Increase	0	0	0	0
Weight Decrease	13.3	8.8	11.6	5.1

Notes
[3] - Diastolic BP (93), Systolic BP (88), Pulse Decrease(100), Pulse Increase (105), Weight Decrease(105)
[4] - Diastolic BP(100), Systolic BP (95), Pulse Decrease(108), Pulse Increase (114), Weight Decrease(114)
[5] - Diastolic BP(99), Systolic BP (93), Pulse Decrease(108), Pulse Increase (112), Weight Decrease(112)
[6] - Diastolic BP(110), Systolic BP (98), Pulse Decrease(112), Pulse Increase (117), Weight Decrease(117)

No statistical analyses for this end point

Secondary: Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Week 10 Through Week 36

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End point title

Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Week 10 Through Week 36

End point description

PCS increase in systolic and diastolic BP was defined as increase of ≥5 mm Hg from baseline (BL) high value to a value above the 95th percentile at post-BL; PCS increase of pulse was defined as >140 and increase of ≥15 from BL high value for age 7-11 and >120 and increase of ≥15 from BL high value for age 12-17; PCS decrease of pulse was defined as <60 and a decrease of ≥25 from BL low value for age 7-11 and <50 and a decrease of ≥15 from BL low value for age 12-17; PCS decrease of weight was defined as decrease of at least 3.5% from BL low value. APD: Participates with normal value before week 10 and at least one non-missing post-Week 10 value, and who are at risk for the specific PCS criteria.

End point type

Secondary

End point timeframe

Week 10 through Week 36

End point values	Duloxetine 60-120 mg	Duloxetine 60-120 mg	Fluoxetine 20-40 mg	Duloxetine 60-120 mg
Number of subjects analysed	73 ^[7]	80 ^[8]	84 ^[9]	82 ^[10]
Units: Percentage of participants
number (not applicable)
Diastolic BP Increase	14.5	4.6	20.3	11.6
Systolic BP Increase	9.4	6.5	7.0	10.5
Pulse Decrease	0	0	0	0
Pulse Increase	1.4	0	0	1.3
Weight Decrease	2.8	9.0	3.7	13.9

Notes
[7] - Diastolic BP (55), Systolic BP (53), Pulse Decrease (68), Pulse Increase (71), Weight Decrease (71)
[8] - Diastolic BP (65), Systolic BP (62), Pulse Decrease (75), Pulse Increase (78), Weight Decrease (78)
[9] - Diastolic BP (64), Systolic BP (57), Pulse Decrease (76), Pulse Increase (81), Weight Decrease (81)
[10] - Diastolic BP (69), Systolic BP (57), Pulse Decrease (73), Pulse Increase (79), Weight Decrease (79)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Entire Study

Adverse event reporting additional description

F1J-MC-HMCL

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

14.0

Reporting group title

Placebo_Acute

Reporting group description

Reporting group title

Duloxetine 60 mg_Acute

Reporting group description

Reporting group title

Fluoxetine_Acute

Reporting group description

Reporting group title

Duloxetine 30 mg_Acute

Reporting group description

Reporting group title

Placebo/Duloxetine 60-120 mg_Extension

Reporting group description

Reporting group title

Fluoxetine_Extension

Reporting group description

Reporting group title

Duloxetine 60/60-120 mg_Extension

Reporting group description

Reporting group title

Duloxetine 30/60-120 mg_Extension

Reporting group description

Serious adverse events	Placebo_Acute	Duloxetine 60 mg_Acute	Fluoxetine_Acute	Duloxetine 30 mg_Acute	Placebo/Duloxetine 60-120 mg_Extension	Fluoxetine_Extension	Duloxetine 60/60-120 mg_Extension	Duloxetine 30/60-120 mg_Extension
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 122 (1.64%)	4 / 108 (3.70%)	6 / 117 (5.13%)	2 / 116 (1.72%)	4 / 82 (4.88%)	1 / 84 (1.19%)	3 / 73 (4.11%)	2 / 81 (2.47%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
intentional overdose
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	2 / 108 (1.85%)	1 / 117 (0.85%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	1 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
road traffic accident
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
wound
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
epilepsy
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
somnolence
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
irritable bowel syndrome
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
stevens-johnson syndrome
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
abnormal behaviour
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
aggression
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	2 / 117 (1.71%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
depression
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
depressive symptom
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
hallucination
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
homicidal ideation
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
self injurious behaviour
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
suicidal ideation
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	2 / 117 (1.71%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
suicide attempt
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	1 / 73 (1.37%)	2 / 81 (2.47%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
tuberculosis of peripheral lymph nodes
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo_Acute	Duloxetine 60 mg_Acute	Fluoxetine_Acute	Duloxetine 30 mg_Acute	Placebo/Duloxetine 60-120 mg_Extension	Fluoxetine_Extension	Duloxetine 60/60-120 mg_Extension	Duloxetine 30/60-120 mg_Extension
Total subjects affected by non serious adverse events
subjects affected / exposed	71 / 122 (58.20%)	76 / 108 (70.37%)	69 / 117 (58.97%)	66 / 116 (56.90%)	52 / 82 (63.41%)	45 / 84 (53.57%)	49 / 73 (67.12%)	46 / 81 (56.79%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
skin papilloma
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Vascular disorders
flushing
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
hot flush
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	1	1	0	0	0	1
Surgical and medical procedures
cholecystectomy
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
influenza immunisation
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
General disorders and administration site conditions
asthenia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0
chest pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
chills
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	1	0	0	0	0	0	1
discomfort
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
energy increased
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
face oedema
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
facial pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
fatigue
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	4 / 122 (3.28%)	5 / 108 (4.63%)	4 / 117 (3.42%)	6 / 116 (5.17%)	6 / 82 (7.32%)	2 / 84 (2.38%)	3 / 73 (4.11%)	2 / 81 (2.47%)
occurrences all number	4	5	4	7	7	2	3	2
feeling abnormal
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
feeling cold
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
feeling hot
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
feeling jittery
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
feeling of body temperature change
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
hyperthermia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
influenza like illness
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
irritability
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	2 / 122 (1.64%)	3 / 108 (2.78%)	0 / 117 (0.00%)	2 / 116 (1.72%)	2 / 82 (2.44%)	1 / 84 (1.19%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	2	3	0	2	2	1	1	1
medical device complication
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	2	0	1	0	0
non-cardiac chest pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	1 / 117 (0.85%)	1 / 116 (0.86%)	1 / 82 (1.22%)	1 / 84 (1.19%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	1	0	1	1	1	1	0	2
pyrexia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	4 / 122 (3.28%)	1 / 108 (0.93%)	0 / 117 (0.00%)	3 / 116 (2.59%)	8 / 82 (9.76%)	1 / 84 (1.19%)	3 / 73 (4.11%)	3 / 81 (3.70%)
occurrences all number	4	1	0	4	8	1	3	4
sluggishness
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	2 / 122 (1.64%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
therapeutic response unexpected
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Immune system disorders
allergy to animal
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
hypersensitivity
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	3 / 117 (2.56%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	2 / 73 (2.74%)	0 / 81 (0.00%)
occurrences all number	0	0	3	0	1	0	2	0
seasonal allergy
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	2 / 84 (2.38%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	2	1	0
Social circumstances
menarche
alternative dictionary used: MedDRA 14.0
subjects affected / exposed ^[1]	1 / 69 (1.45%)	0 / 60 (0.00%)	0 / 61 (0.00%)	0 / 47 (0.00%)	0 / 49 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
victim of sexual abuse
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Reproductive system and breast disorders
cervical dysplasia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed ^[2]	1 / 69 (1.45%)	0 / 60 (0.00%)	0 / 61 (0.00%)	0 / 47 (0.00%)	0 / 49 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
dysmenorrhoea
alternative dictionary used: MedDRA 14.0
subjects affected / exposed ^[3]	3 / 69 (4.35%)	2 / 60 (3.33%)	1 / 61 (1.64%)	1 / 47 (2.13%)	2 / 49 (4.08%)	1 / 39 (2.56%)	1 / 39 (2.56%)	1 / 32 (3.13%)
occurrences all number	3	3	2	1	2	1	1	1
menstruation delayed
alternative dictionary used: MedDRA 14.0
subjects affected / exposed ^[4]	0 / 69 (0.00%)	0 / 60 (0.00%)	0 / 61 (0.00%)	1 / 47 (2.13%)	0 / 49 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
menstruation irregular
alternative dictionary used: MedDRA 14.0
subjects affected / exposed ^[5]	0 / 69 (0.00%)	1 / 60 (1.67%)	0 / 61 (0.00%)	0 / 47 (0.00%)	0 / 49 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
pruritus genital
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Respiratory, thoracic and mediastinal disorders
asthma
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0
cough
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	3 / 122 (2.46%)	2 / 108 (1.85%)	2 / 117 (1.71%)	4 / 116 (3.45%)	3 / 82 (3.66%)	5 / 84 (5.95%)	2 / 73 (2.74%)	1 / 81 (1.23%)
occurrences all number	3	2	2	4	3	5	2	1
epistaxis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	3 / 117 (2.56%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	1	0	3	0	1	0	1	0
nasal congestion
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	2 / 117 (1.71%)	3 / 116 (2.59%)	3 / 82 (3.66%)	2 / 84 (2.38%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	1	0	2	3	3	2	1	1
oropharyngeal pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	3 / 122 (2.46%)	3 / 108 (2.78%)	6 / 117 (5.13%)	2 / 116 (1.72%)	2 / 82 (2.44%)	0 / 84 (0.00%)	3 / 73 (4.11%)	1 / 81 (1.23%)
occurrences all number	3	3	6	2	2	0	4	1
rhinitis allergic
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	1	1	0	0	0	0	1	0
rhinitis seasonal
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
rhinorrhoea
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	1 / 117 (0.85%)	1 / 116 (0.86%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	1	1	1	1	0	0	2
sinus congestion
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	1	1	0	0	0	0	1	0
sneezing
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
snoring
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
upper respiratory tract inflammation
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
yawning
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	2 / 116 (1.72%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	2	0	0	0	0
Psychiatric disorders
abnormal behaviour
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	2 / 117 (1.71%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	3	0	0	0	1	0
abnormal dreams
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	2 / 117 (1.71%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	2	1	0	0	0	0
aggression
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	0	1	0	0	1	0	1	1
agitation
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
anger
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
anorexia nervosa
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
anxiety
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	1 / 108 (0.93%)	1 / 117 (0.85%)	3 / 116 (2.59%)	2 / 82 (2.44%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	1	1	3	2	0	0	0
bipolar disorder
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
confusional state
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
depression
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	1 / 82 (1.22%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	1	0	1	0
derealisation
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
emotional disorder
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
hallucination, auditory
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
hallucination, visual
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
hallucinations, mixed
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
hypomania
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	0	0	1	0	0	0	1	1
impulsive behaviour
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
inappropriate affect
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
initial insomnia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	2 / 108 (1.85%)	1 / 117 (0.85%)	1 / 116 (0.86%)	1 / 82 (1.22%)	1 / 84 (1.19%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	1	2	1	1	1	1	1	0
insomnia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	4 / 122 (3.28%)	3 / 108 (2.78%)	5 / 117 (4.27%)	3 / 116 (2.59%)	2 / 82 (2.44%)	1 / 84 (1.19%)	2 / 73 (2.74%)	4 / 81 (4.94%)
occurrences all number	4	3	5	3	2	1	2	5
intentional drug misuse
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
intentional self-injury
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	2 / 108 (1.85%)	2 / 117 (1.71%)	2 / 116 (1.72%)	1 / 82 (1.22%)	0 / 84 (0.00%)	2 / 73 (2.74%)	2 / 81 (2.47%)
occurrences all number	1	3	2	2	1	0	3	2
middle insomnia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	2 / 82 (2.44%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	1	0	0	1	2	0	0	1
mood swings
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	2	0	0	1	0	0	0	0
nervousness
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
nightmare
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	2 / 108 (1.85%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	2 / 73 (2.74%)	0 / 81 (0.00%)
occurrences all number	0	2	0	0	0	0	2	0
pyromania
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
restlessness
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	2 / 117 (1.71%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	1	0	2	0	0	0	0	1
sleep disorder
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	2 / 122 (1.64%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
somnambulism
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	2	0	0	0	0
suicidal ideation
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	2 / 122 (1.64%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	2 / 84 (2.38%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	2	0	0	0	1	3	1	1
tachyphrenia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
tearfulness
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
terminal insomnia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
tic
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Investigations
blood creatine phosphokinase increased
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	1 / 84 (1.19%)	2 / 73 (2.74%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	1	2	0
blood uric acid increased
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
electrocardiogram qt prolonged
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
heart rate increased
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	2 / 73 (2.74%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	2	0
human papilloma virus test positive
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
lymph node palpable
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
weight decreased
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	1 / 116 (0.86%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	1	1	0	0	0
weight increased
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	2 / 73 (2.74%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	2	0
Injury, poisoning and procedural complications
accidental exposure
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
accidental overdose
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	1 / 82 (1.22%)	1 / 84 (1.19%)	0 / 73 (0.00%)	2 / 81 (2.47%)
occurrences all number	1	0	0	1	1	1	0	2
animal bite
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0
concussion
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
contusion
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	1 / 108 (0.93%)	0 / 117 (0.00%)	1 / 116 (0.86%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	1	0	1	2	0	0	0
excoriation
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	2 / 84 (2.38%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	2	0	0
facial bones fracture
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
fall
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0
hand fracture
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0
head injury
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	1	0	0	1	0	0	1
inappropriate schedule of drug administration
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
incorrect dose administered
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	3 / 117 (2.56%)	1 / 116 (0.86%)	1 / 82 (1.22%)	4 / 84 (4.76%)	5 / 73 (6.85%)	3 / 81 (3.70%)
occurrences all number	0	1	3	1	1	4	5	3
intentional overdose
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
joint dislocation
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
joint injury
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
joint sprain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	1 / 108 (0.93%)	1 / 117 (0.85%)	0 / 116 (0.00%)	1 / 82 (1.22%)	2 / 84 (2.38%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	1	1	1	0	1	2	0	1
laceration
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	1	0	1	0
limb injury
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	2 / 84 (2.38%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	2	1	0
muscle rupture
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
muscle strain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
periorbital haematoma
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0
post concussion syndrome
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
procedural dizziness
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
procedural pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
road traffic accident
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
skeletal injury
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
stress fracture
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
sunburn
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	1	1
thermal burn
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	1 / 117 (0.85%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	1	1	0	0	0	0
upper limb fracture
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
wrist fracture
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	2 / 84 (2.38%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0
Cardiac disorders
palpitations
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Nervous system disorders
aphasia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
cerebral disorder
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
crying
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	1 / 84 (1.19%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	2	1	0
delayed sleep phase
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
disturbance in attention
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
dizziness
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	8 / 122 (6.56%)	9 / 108 (8.33%)	5 / 117 (4.27%)	10 / 116 (8.62%)	7 / 82 (8.54%)	2 / 84 (2.38%)	2 / 73 (2.74%)	6 / 81 (7.41%)
occurrences all number	8	9	5	11	7	2	2	6
headache
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	16 / 122 (13.11%)	19 / 108 (17.59%)	22 / 117 (18.80%)	20 / 116 (17.24%)	11 / 82 (13.41%)	10 / 84 (11.90%)	6 / 73 (8.22%)	4 / 81 (4.94%)
occurrences all number	19	22	26	27	13	14	8	4
hyperreflexia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
hypersomnia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	2 / 116 (1.72%)	1 / 82 (1.22%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	2	1	1	0	0
memory impairment
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	1	1	0	0
migraine
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	1 / 84 (1.19%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	1	0	0	1	0	1	1	0
paraesthesia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
poor quality sleep
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	0	0	1	0	0	0	1	1
post-traumatic headache
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
psychomotor hyperactivity
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	1	0	0	1	0	0
sedation
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	5 / 108 (4.63%)	0 / 117 (0.00%)	2 / 116 (1.72%)	1 / 82 (1.22%)	0 / 84 (0.00%)	2 / 73 (2.74%)	0 / 81 (0.00%)
occurrences all number	0	5	0	2	1	0	3	0
sensory disturbance
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
sinus headache
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	1	0	0	0	0	1
somnolence
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	6 / 122 (4.92%)	11 / 108 (10.19%)	4 / 117 (3.42%)	3 / 116 (2.59%)	2 / 82 (2.44%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	6	11	4	3	2	0	1	0
syncope
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0
tension headache
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0
tremor
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Blood and lymphatic system disorders
anaemia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
iron deficiency anaemia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
thrombocytosis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Ear and labyrinth disorders
ear pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	2 / 84 (2.38%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	0	1	0	1	0	2	1	1
motion sickness
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
tinnitus
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	2 / 117 (1.71%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0
vertigo
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	2 / 117 (1.71%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	2	0	0	0	1	0
Eye disorders
astigmatism
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
blepharospasm
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
conjunctivitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
conjunctivitis allergic
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
eye pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
hypermetropia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
mydriasis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
myopia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
vision blurred
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0
Gastrointestinal disorders
abdominal discomfort
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	1 / 117 (0.85%)	4 / 116 (3.45%)	0 / 82 (0.00%)	0 / 84 (0.00%)	3 / 73 (4.11%)	0 / 81 (0.00%)
occurrences all number	0	1	1	5	0	0	3	0
abdominal distension
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
abdominal pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	3 / 108 (2.78%)	0 / 117 (0.00%)	2 / 116 (1.72%)	0 / 82 (0.00%)	1 / 84 (1.19%)	4 / 73 (5.48%)	1 / 81 (1.23%)
occurrences all number	0	3	0	2	0	1	4	1
abdominal pain lower
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
abdominal pain upper
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	9 / 122 (7.38%)	13 / 108 (12.04%)	10 / 117 (8.55%)	10 / 116 (8.62%)	4 / 82 (4.88%)	7 / 84 (8.33%)	6 / 73 (8.22%)	6 / 81 (7.41%)
occurrences all number	12	14	10	10	4	7	8	7
constipation
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	2 / 73 (2.74%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	1	0	2	1
diarrhoea
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	2 / 122 (1.64%)	4 / 108 (3.70%)	3 / 117 (2.56%)	9 / 116 (7.76%)	2 / 82 (2.44%)	5 / 84 (5.95%)	1 / 73 (1.37%)	5 / 81 (6.17%)
occurrences all number	3	4	3	9	2	5	1	7
dry mouth
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	2 / 122 (1.64%)	3 / 108 (2.78%)	1 / 117 (0.85%)	2 / 116 (1.72%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	2	3	1	2	0	0	1	0
dyspepsia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	3 / 108 (2.78%)	1 / 117 (0.85%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	4	1	0	1	0	0	0
faecal incontinence
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
flatulence
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0
food poisoning
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	1	0	0	0	0	0	1
frequent bowel movements
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
gastritis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
gastrointestinal sounds abnormal
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
gastrooesophageal reflux disease
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
gingival bleeding
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
gingival pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0
nausea
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	11 / 122 (9.02%)	18 / 108 (16.67%)	11 / 117 (9.40%)	21 / 116 (18.10%)	8 / 82 (9.76%)	3 / 84 (3.57%)	6 / 73 (8.22%)	13 / 81 (16.05%)
occurrences all number	11	20	12	22	10	5	7	14
stomatitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
teething
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
tooth crowding
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
tooth impacted
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0
toothache
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	2 / 122 (1.64%)	0 / 108 (0.00%)	3 / 117 (2.56%)	0 / 116 (0.00%)	1 / 82 (1.22%)	1 / 84 (1.19%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	2	0	3	0	1	1	1	1
vomiting
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	3 / 122 (2.46%)	5 / 108 (4.63%)	2 / 117 (1.71%)	7 / 116 (6.03%)	8 / 82 (9.76%)	8 / 84 (9.52%)	4 / 73 (5.48%)	10 / 81 (12.35%)
occurrences all number	3	6	2	8	9	8	4	13
Hepatobiliary disorders
biliary dyskinesia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
hepatic steatosis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Skin and subcutaneous tissue disorders
acne
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	1 / 116 (0.86%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	1	1	0	0	0
alopecia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
dermatitis contact
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	1 / 117 (0.85%)	1 / 116 (0.86%)	1 / 82 (1.22%)	1 / 84 (1.19%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	1	0	2	1	1	1	1	1
eczema
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0
heat rash
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
hyperhidrosis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	2 / 108 (1.85%)	1 / 117 (0.85%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	2	1	1	0	0	0	0
ingrown hair
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
pain of skin
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
pruritus
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	2 / 108 (1.85%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	1	2	0	2	0	0	1	1
rash
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	1 / 108 (0.93%)	1 / 117 (0.85%)	1 / 116 (0.86%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	1	1	1	1	0	0	0
rash macular
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	2 / 116 (1.72%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0
rash maculo-papular
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
stevens-johnson syndrome
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
trichorrhexis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
urticaria
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	1	0	0	1	0	0
Renal and urinary disorders
enuresis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	1	0	0	1
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	3 / 122 (2.46%)	1 / 108 (0.93%)	1 / 117 (0.85%)	1 / 116 (0.86%)	2 / 82 (2.44%)	0 / 84 (0.00%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	3	1	1	1	2	0	1	2
back pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	2 / 108 (1.85%)	2 / 117 (1.71%)	2 / 116 (1.72%)	2 / 82 (2.44%)	1 / 84 (1.19%)	2 / 73 (2.74%)	0 / 81 (0.00%)
occurrences all number	0	2	2	2	2	2	2	0
flank pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
joint hyperextension
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
muscle spasms
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	2 / 116 (1.72%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	2	0	0	0	0
muscular weakness
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
musculoskeletal stiffness
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
myalgia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
neck pain
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0
pain in extremity
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	2 / 122 (1.64%)	1 / 108 (0.93%)	3 / 117 (2.56%)	0 / 116 (0.00%)	2 / 82 (2.44%)	1 / 84 (1.19%)	2 / 73 (2.74%)	1 / 81 (1.23%)
occurrences all number	2	1	3	0	2	1	3	1
temporomandibular joint syndrome
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Infections and infestations
abscess
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
abscess limb
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
acarodermatitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
acute tonsillitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
bronchitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	2 / 84 (2.38%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0
cat scratch disease
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
cellulitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
conjunctivitis infective
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
cystitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
ear infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	1 / 84 (1.19%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	1	0	0	1	2	0	1
folliculitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	1	0	1
fungal infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	1	1
furuncle
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0
gastric infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
gastroenteritis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	3 / 108 (2.78%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	1 / 73 (1.37%)	2 / 81 (2.47%)
occurrences all number	0	3	0	0	1	0	1	2
gastroenteritis viral
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	1 / 116 (0.86%)	1 / 82 (1.22%)	0 / 84 (0.00%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	0	2	0	1	1	0	1	1
gastrointestinal infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
gastrointestinal viral infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	1 / 84 (1.19%)	1 / 73 (1.37%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	1	1	1	0
hordeolum
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	2 / 82 (2.44%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	0	2	0	0	0
infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
infectious mononucleosis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
influenza
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	2 / 122 (1.64%)	1 / 108 (0.93%)	1 / 117 (0.85%)	3 / 116 (2.59%)	3 / 82 (3.66%)	2 / 84 (2.38%)	3 / 73 (4.11%)	1 / 81 (1.23%)
occurrences all number	2	1	1	3	4	3	4	1
kidney infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
laryngitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
nasopharyngitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	3 / 122 (2.46%)	3 / 108 (2.78%)	7 / 117 (5.98%)	4 / 116 (3.45%)	3 / 82 (3.66%)	7 / 84 (8.33%)	3 / 73 (4.11%)	6 / 81 (7.41%)
occurrences all number	3	3	8	4	3	8	3	7
oral herpes
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
otitis externa
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
otitis media
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	1 / 84 (1.19%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	1	1	0	1
paronychia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	0 / 117 (0.00%)	2 / 116 (1.72%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	1	0	0	3	0	0	0	0
pharyngitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	0 / 108 (0.00%)	1 / 117 (0.85%)	1 / 116 (0.86%)	1 / 82 (1.22%)	1 / 84 (1.19%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	1	0	1	1	2	1	1	1
pharyngitis streptococcal
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	1 / 122 (0.82%)	1 / 108 (0.93%)	1 / 117 (0.85%)	2 / 116 (1.72%)	1 / 82 (1.22%)	1 / 84 (1.19%)	3 / 73 (4.11%)	1 / 81 (1.23%)
occurrences all number	1	1	1	2	1	1	3	1
pharyngotonsillitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0
respiratory tract infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
rhinitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
sinusitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	3 / 122 (2.46%)	1 / 108 (0.93%)	0 / 117 (0.00%)	1 / 116 (0.86%)	2 / 82 (2.44%)	1 / 84 (1.19%)	1 / 73 (1.37%)	1 / 81 (1.23%)
occurrences all number	3	1	0	1	2	1	1	1
skin infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	1	0	1
staphylococcal skin infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
subcutaneous abscess
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
tonsillitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	1 / 116 (0.86%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	2 / 81 (2.47%)
occurrences all number	0	0	0	1	0	0	0	2
upper respiratory tract infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	6 / 122 (4.92%)	1 / 108 (0.93%)	3 / 117 (2.56%)	6 / 116 (5.17%)	2 / 82 (2.44%)	2 / 84 (2.38%)	5 / 73 (6.85%)	4 / 81 (4.94%)
occurrences all number	6	1	3	7	3	2	7	6
urinary tract infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	1	0	0	0	0	0	1
vaginal infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed ^[6]	0 / 69 (0.00%)	1 / 60 (1.67%)	0 / 61 (0.00%)	0 / 47 (0.00%)	0 / 49 (0.00%)	0 / 39 (0.00%)	0 / 39 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
varicella
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	1	0	0	1
viral infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	1 / 108 (0.93%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	1	0	0	0	2	0	0
viral pharyngitis
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
viral upper respiratory tract infection
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	1 / 117 (0.85%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	2	0	1	0	0	1
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	4 / 122 (3.28%)	6 / 108 (5.56%)	6 / 117 (5.13%)	10 / 116 (8.62%)	4 / 82 (4.88%)	1 / 84 (1.19%)	0 / 73 (0.00%)	3 / 81 (3.70%)
occurrences all number	4	6	6	10	4	1	0	3
dehydration
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	0 / 82 (0.00%)	0 / 84 (0.00%)	0 / 73 (0.00%)	1 / 81 (1.23%)
occurrences all number	0	0	0	0	0	0	0	1
diabetes mellitus
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
hyperlipidaemia
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	0 / 122 (0.00%)	0 / 108 (0.00%)	0 / 117 (0.00%)	0 / 116 (0.00%)	1 / 82 (1.22%)	0 / 84 (0.00%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
increased appetite
alternative dictionary used: MedDRA 14.0
subjects affected / exposed	2 / 122 (1.64%)	0 / 108 (0.00%)	1 / 117 (0.85%)	1 / 116 (0.86%)	1 / 82 (1.22%)	1 / 84 (1.19%)	0 / 73 (0.00%)	0 / 81 (0.00%)
occurrences all number	2	0	1	1	1	1	0	0

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

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Double-Blind, Efficacy and Safety Study of Duloxetine Versus Placebo in the Treatment of Children and Adolescents With Major Depressive Disorder

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint

Primary: Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint

Secondary: Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint

Secondary: Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 36 Endpoint

Secondary: Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint

Secondary: Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 10 Endpoint

Secondary: Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint

Secondary: Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 10 Endpoint

Secondary: Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint

Secondary: Change From Week 10 in Children's Depression Rating Scale-Revised (CDRS-R) Subscale Score at Week 36 Endpoint

Secondary: Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint

Secondary: Change From Baseline in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 10 Endpoint

Secondary: Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint

Secondary: Change From Week 10 in Clinical Global Impressions of Severity (CGI-Severity) Scale at Week 36 Endpoint

Secondary: Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10

Secondary: Number of Participants With Suicidal Ideation or Suicidal Behavior Baseline Through Week 10

Secondary: Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36

Secondary: Number of Participants With Suicidal Ideation or Suicidal Behavior Week 10 Through Week 36

Secondary: Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10

Secondary: Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Baseline Through Week 10

Secondary: Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36

Secondary: Number of Participants With Potentially Clinically Significant Hepatic Laboratory Results Any Time Week 10 Through Week 36

Secondary: Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Baseline Through Week 10

Secondary: Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Baseline Through Week 10

Secondary: Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Week 10 Through Week 36

Secondary: Percentage of Participants With Potentially Clinically Significant (PCS) Changes in Systolic Blood Pressure (BP), Diastolic BP, Pulse, and Weight Any Time Week 10 Through Week 36

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Double-Blind, Efficacy and Safety Study of Duloxetine Versus Placebo in the Treatment of Children and Adolescents With Major Depressive Disorder