A Study of TD-9855 in Adults With Attention-Deficit/Hyper... | NCT01458340

Label	Type	Intervention Names
TD-9855 Dose 1	Experimental	Drug: TD-9855
Placebo	Experimental	Drug: Placebo
TD-9855 Dose 2	Experimental	Drug: TD-9855

Name	Type	Description	Arm Group Labels	Other Names
TD-9855	Drug	Once daily	TD-9855 Dose 1
TD-9855

Measure	Description	Time Frame
Change From Baseline in AISRS Total Score at Day 42	The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. It is a clinician-administered scale that measures all 18 symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The total score ranges from 0 to 54 with a negative change from baseline indicating an improvement in severity/reduction in symptoms.	Baseline and Day 42

Measure	Description	Time Frame
Change From Baseline in BDEFS-SF: Self Report Total Score at Day 42	The BDEFS-SF: Self-Report is an empirically based tool for evaluating dimensions of adult executive functioning in daily life. The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. The score for each item ranges from 1 (never) to 4 (very often). The total score on the BDEFS-SF ranges from 20 to 80 with a negative change from baseline indicating an improvement in functioning.

Name	Affiliation	Role
Medical Monitor	Theravance Biopharma	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Florida Clinical Research Center, LLC		Bradenton	Florida	34201	United States
Clinical Neuroscience Solutions, Inc.

PubMed Identifier	Type	Citation	Retractions
32856281	Derived	Kanodia J, Lo A, Baldwin RM, Graham RA, Bourdet DL. Pharmacokinetics of Ampreloxetine, a Norepinephrine Reuptake Inhibitor, in Healthy Subjects and Adults with Attention-Deficit/Hyperactive Disorder or Fibromyalgia Pain. Clin Pharmacokinet. 2021 Jan;60(1):121-131. doi: 10.1007/s40262-020-00918-7.

ID	Title	Description
FG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
FG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in AISRS Total Score at Day 42

The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. It is a clinician-administered scale that measures all 18 symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The total score ranges from 0 to 54 with a negative change from baseline indicating an improvement in severity/reduction in symptoms.

The ITT population included all randomized participants.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules once daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Units	Counts
Participants	OG00097 OG00199 OG00299

Title

Denominators

Categories

Title	Measurements
	OG000-12.1± 1.21 OG001-11.7± 1.17 OG002-12.2± 1.18

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Model for Repeated Measures (MMRM)	One-sided p-values were obtained from the pairwise comparisons between TD-9855 group and placebo group based on the final model.	0.6026	α=0.05 significance level.	LS Mean Difference	0.4	Standard Error of the Mean	1.69	1-Sided	95		3.2					Superiority

Secondary

Change From Baseline in BDEFS-SF: Self Report Total Score at Day 42

The BDEFS-SF: Self-Report is an empirically based tool for evaluating dimensions of adult executive functioning in daily life. The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. The score for each item ranges from 1 (never) to 4 (very often). The total score on the BDEFS-SF ranges from 20 to 80 with a negative change from baseline indicating an improvement in functioning.

The ITT population included all randomized participants. Only participants with data available for analysis and with a with baseline BDEFS-SF Total Score >= 45 are included.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received matching placebo as oral capsules once per day from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules once per day from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules once per day from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to take the 10 mg from Day 8 to Day 42.

Secondary

Change From Baseline in AISRS Inattentive Subscale at Day 42

The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. The AISRS inattentive subscale that measures all 9 inattentive symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The AISRS inattentive subscale score ranges from 0 to 27 with a negative change from baseline indicating an improvement in severity/reduction in symptoms.

The ITT population included all randomized participants. Only participants with data available for analysis are included.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Secondary

Change From Baseline in AISRS Hyperactive-impulsive Subscale at Day 42

The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. The AISRS hyperactive-impulsive subscale measures all 9 hyperactive/impulsive symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The AISRS hyperactive-impulsive subscale score ranges from 0 to 27 with a negative change from baseline indicating an improvement in severity/reduction in symptoms.

The ITT population included all randomized participants. Only participants with data available for analysis are included.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Secondary

Percentage of Participants With an AISRS Response at Day 42

The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. The AISRS total scale measures all 18 symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The total score ranges from 0 to 54. A responder is defined as a participant with >=30% reduction from baseline in AISRS total score.

The ITT population included all randomized participants. Only participants with data available for analysis are included.

Posted

Number

percentage of participants

Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Secondary

Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Day 42

The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participants' illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating 1=normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7,extremely ill. A negative change from baseline indicates a reduction in illness.

The ITT population included all randomized participants. Only participants with data available for analysis are included.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Secondary

Change From Baseline in Adult ADHD Self-Report Scale (ASRS) Total Score at Day 42

The ASRS is a checklist consisting of the 18 Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV-TR) criteria in which participants rank frequency of each criterion from never (0) to very often (4). The ASRS total score ranges from 0-72 with a negative change from baseline indicating a reduction in frequency of symptoms.

The ITT population included all randomized participants. Only participants with data available for analysis are included.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Secondary

Change From Baseline in ASRS Inattentive Subscale at Day 42

The ASRS inattentive subscale is a checklist consisting of 9 DSM-IV-TR inattentive criteria in which participants rank frequency of each criterion from never (0) to very often (4). The ASRS inattentive subscale score ranges from 0-36 with a negative change from baseline indicating a reduction in frequency of symptoms.

The ITT population included all randomized participants. Only participants with data available for analysis are included.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Secondary

Change From Baseline in ASRS Hyperactive-impulsive Subscale at Day 42

The ASRS hyperactive-impulsive subscale is a checklist consisting of 9 DSM-IV-TR hyperactive/impulsive criteria in which participants rank frequency of each criterion from never (0) to very often (4). The ASRS hyperactive-impulsive subscale score ranges from 0-36 with a negative change from baseline indicating a reduction in frequency of symptoms.

The ITT population included all randomized participants. Only participants with data available for analysis are included.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Secondary

Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Day 42

MADRS is a 10-item investigator-rated scale that assesses the range of symptoms that are most frequently observed in patients with major depression. The 10 selected items are rated on a scale of 0 (no depression) to 6 (highest level of depression) with anchors at 2-point intervals. Total scores on the MADRS range from 0 to 60 with a negative change from baseline indicating an improvement in levels of depression.

The ITT population included all randomized participants. Only participants with data available for analysis are included.

Posted

Mean

Standard Deviation

score on a scale

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Secondary

Percentage of Participants With a Reliable Change on the BDEFS-SF at Day 42

The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. The score for each item ranges from 1 (never) to 4 (very often). The total score on the BDEFS-SF ranges from 20 to 80. A reliable change is defined as a decrease in total BDEFS-SF score of 12 or more relative to the baseline value.

The ITT population included all randomized participants. Only participants with data available for analysis are included.

Posted

Number

percentage of participants

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Secondary

Percentage of Participants With a Reliable Change and Normalized Score on the BDEFS-SF at Day 42

The ITT population included all randomized participants. Only participants with data available for analysis and with a with baseline BDEFS-SF Total Score >= 45 are included.

Posted

Number

percentage of participants

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Secondary

Change From Baseline in BDEFS-SF Symptom Count at Day 42

The BDEFS-SF is used to score how frequently the participants experience problems involved in time management; organization and problem solving; self restraint; self motivation; and self-regulation of emotions. A negative change from baseline in symptom count indicates an improvement in functioning. Only symptoms rated as occurring often or very often on the BDEFS-SF are included in the symptom count. Mean change from baseline in symptom count is reported

The ITT population included all randomized participants. Only participants with data available for analysis are included.

Posted

Mean

Standard Deviation

count of symptoms

Baseline and Day 42

ID	Title	Description
OG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
OG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
OG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG00017 affected97 at risk EG00121 affected98 at risk EG00221 affected98 at risk
Dizziness	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0009 affected97 at risk EG0018 affected98 at risk EG00218 affected98 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0004 affected97 at risk EG0019 affected98 at risk EG00213 affected98 at risk
Fatigue	General disorders	MedDRA 14.1	Systematic Assessment	EG0006 affected97 at risk EG0017 affected98 at risk EG0029 affected98 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0003 affected97 at risk EG0017 affected98 at risk EG00210 affected98 at risk
Insomnia	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0008 affected97 at risk EG0013 affected98 at risk EG0023 affected98 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0006 affected97 at risk EG0014 affected98 at risk EG0022 affected98 at risk
Middle insomnia	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0013 affected98 at risk EG0026 affected98 at risk
Nasopharyngitis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0003 affected97 at risk EG0013 affected98 at risk EG0025 affected98 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0016 affected98 at risk EG0023 affected98 at risk
Somnolence	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0006 affected97 at risk EG0012 affected98 at risk EG0022 affected98 at risk
Anxiety	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0005 affected97 at risk EG0012 affected98 at risk EG0021 affected98 at risk
Dizziness postural	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0026 affected98 at risk
Postural orthostatic tachycardia syndrome	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0013 affected98 at risk EG0024 affected98 at risk
Tachycardia	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0012 affected98 at risk EG0024 affected98 at risk
Palpitations	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0012 affected98 at risk EG0020 affected98 at risk
Bundle branch block right	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Ear disorder	Ear and labyrinth disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Blepharospasm	Eye disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0012 affected98 at risk EG0020 affected98 at risk
Dry eye	Eye disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Ocular hyperaemia	Eye disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Visual impairment	Eye disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0013 affected98 at risk EG0023 affected98 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0011 affected98 at risk EG0024 affected98 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0013 affected98 at risk EG0022 affected98 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0014 affected98 at risk EG0020 affected98 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Toothache	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0012 affected98 at risk EG0020 affected98 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Aphthous stomatitis	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Irritability	General disorders	MedDRA 14.1	Systematic Assessment	EG0003 affected97 at risk EG0012 affected98 at risk EG0022 affected98 at risk
Feeling jittery	General disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Feeling hot	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0013 affected98 at risk EG0020 affected98 at risk
Thirst	General disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0022 affected98 at risk
Sluggishness	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0012 affected98 at risk EG0020 affected98 at risk
Asthenia	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Chest discomfort	General disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Chest pain	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Chills	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Cyst	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Multiple allergies	Immune system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Seasonal allergy	Immune system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Sinusitis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0010 affected98 at risk EG0022 affected98 at risk
Gastroenteritis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0003 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Bronchitis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Otitis externa	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Viral infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Fungal infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Gingival infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Hordeolum	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Otitis media	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Tooth abscess	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0022 affected98 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Excoriation	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0012 affected98 at risk EG0020 affected98 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Sunburn	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0012 affected98 at risk EG0020 affected98 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Back injury	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Burns first degree	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Muscle rupture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Skeletal injury	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Heart rate increased	Investigations	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0024 affected98 at risk
Blood pressure increased	Investigations	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Blood pressure orthostatic increased	Investigations	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Blood thyroid stimulating hormone decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Blood thyroid stimulating hormone increased	Investigations	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Urine output decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Increased appetite	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0003 affected97 at risk EG0013 affected98 at risk EG0021 affected98 at risk
Fluid retention	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Polydipsia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0013 affected98 at risk EG0022 affected98 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0022 affected98 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0012 affected98 at risk EG0021 affected98 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Plantar fasciitis	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Sedation	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Dysgeusia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Migraine	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0022 affected98 at risk
Paraesthesia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Sinus headache	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Tremor	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Akathisia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Amnesia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Disturbance in attention	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Head discomfort	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Lethargy	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Memory impairment	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Poor quality sleep	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Retinal migraine	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Syncope	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Tension headache	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Initial insomnia	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0013 affected98 at risk EG0024 affected98 at risk
Libido decreased	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0012 affected98 at risk EG0020 affected98 at risk
Abnormal dreams	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Agitation	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Depression	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0012 affected98 at risk EG0020 affected98 at risk
Libido increased	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0022 affected98 at risk
Restlessness	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Tension	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0002 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Anorgasmia	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Apathy	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Attention deficit/hyperactivity disorder	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Derealisation	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Elevated mood	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Mood altered	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Nervousness	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Nightmare	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Personality change	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Sleep disorder	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Terminal insomnia	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Urine flow decreased	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0022 affected98 at risk
Dysuria	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Glycosuria	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Nocturia	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Urinary hesitation	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Ejaculation failure	Reproductive system and breast disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Epididymitis	Reproductive system and breast disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Scrotal disorder	Reproductive system and breast disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0023 affected98 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0022 affected98 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Tonsillar hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Upper respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0022 affected98 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0012 affected98 at risk EG0021 affected98 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0021 affected98 at risk
Blister	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Cold sweat	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Ingrown hair	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0010 affected98 at risk EG0020 affected98 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Tooth extraction	Surgical and medical procedures	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk
Liposuction	Surgical and medical procedures	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Mammoplasty	Surgical and medical procedures	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Skin lesion excision	Surgical and medical procedures	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0021 affected98 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0014 affected98 at risk EG0020 affected98 at risk
Flushing	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected97 at risk EG0010 affected98 at risk EG0022 affected98 at risk
Hot flush	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0001 affected97 at risk EG0011 affected98 at risk EG0020 affected98 at risk

ID	Term
D019958	Attention Deficit and Disruptive Behavior Disorders
D065886	Neurodevelopmental Disorders
D001523	Mental Disorders

ID	Title	Description
BG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.
BG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.
BG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received a matching placebo as oral capsules daily from Day 1 to Day 42.	97	1	97	68	97
EG001	TD-9855 5mg	Participants received 5 mg TD-9855 as oral capsules daily from Day 1 to Day 42.	98	0	98	75	98
EG002	TD-9855 20 mg	Participants received 10 mg TD-9855 as oral capsules daily from Day 1 to Day 7. Participants' doses were increased to 20 mg from Day 8 to Day 42 based on the safety and tolerability of the 10 mg dose. Participants who in the investigator's opinion were not able to tolerate the 20 mg dose, continued to receive the 10 mg dose from Day 8 to Day 42.	98	0	98	80	98