A Study Of The Efficacy And Safety Of CP-601,927 Augmenta... | NCT01098240

Label	Type	Description	Intervention Names
Active Treatment	Experimental	CP-601,927	Drug: CP-601,927
Placebo	Placebo Comparator	Placebo	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
CP-601,927	Drug	CP-601,927 1-2 mg twice per day, oral 1 mg tablets, for 6 weeks.	Active Treatment

Measure	Description	Time Frame
Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14	MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms).	Week 8 (double-blind baseline ) and week 14 (week 6 of double-blind phase)

Measure	Description	Time Frame
Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13	MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms).	Week 8 (double-blind baseline) and weeks 9 through 13

Measure	Description	Time Frame
The Sheehan Suicidality Tracking Scale (STS)	The Sheehan Suicidality Tracking Scale (STS) measures treatment-emergent suicidal ideation as well as behaviors. It can be administered by a clinician or filled in by a participant. Prior to analysis, the STS was mapped to the Columbia Classification Algorithm of Suicide Assessment(C-CASA) categories, which has 9-item including completed suicide, suicide attempt, preparatory acts, suicidal ideation, self-injurious behavior, self-injurious no intent, unknown fatal,unknown non-fatal or other not deliberate. Participants who were mapped to C-CASA items were reported.

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

Facility	Status	City	State	ZIP	Country	Contacts
Arkansas Psychiatric Clinic Clinical Research Trials, P.A.		Little Rock	Arkansas	72223	United States

PubMed Identifier	Type	Citation	Retractions
25422883	Derived	Fava M, Ramey T, Pickering E, Kinrys G, Boyer S, Altstiel L. A randomized, double-blind, placebo-controlled phase 2 study of the augmentation of a nicotinic acetylcholine receptor partial agonist in depression: is there a relationship to leptin levels? J Clin Psychopharmacol. 2015 Feb;35(1):51-6. doi: 10.1097/JCP.0000000000000245.

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

ID	Title	Description
FG000	Open-Label Antidepressant Treatment (ADT)	Participants treated with 1 of 5 allowed antidepressant agents in accordance with current product labeling, targeting the following doses by the end of week 2: escitalopram (Lexapro) (10-20 milligram/day [mg/d]), citalopram (Celexa) (20-40 mg/d), fluoxetine (Prozac, Sarafem) (20-60 mg/d), paroxetine controlled-release (CR) (Paxil CR) (37.5-62.5 mg/d), sertraline (Zoloft) (100-200 mg/d), for up to 8 weeks in open-label phase.

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 Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14

MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms).

The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe.

Posted

Mean

Standard Deviation

Units on a scale

Week 8 (double-blind baseline ) and week 14 (week 6 of double-blind phase)

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Units	Counts
Participants	OG00077 OG00185

Title

Denominators

Categories

Week 8 (double-blind baseline)

- ParticipantsOG00077
- ParticipantsOG00185

Title	Measurements
	OG00029.5± 6.00

Secondary

Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13

Posted

Mean

Standard Deviation

Units on a scale

Week 8 (double-blind baseline) and weeks 9 through 13

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Secondary

Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14

The HAM-D25 is the 25-item version of a scale used to assess the range of depressive symptoms including depressed mood, work and activities, sleep, suicidal thinking, psychomotor agitation/retardation, appetite, sexual interest, anxiety, somatic symptoms, and cognitive symptoms. The items on the HAM-D were rated on a scale of 0-2 or 0-4, for a total numeric range of scores from 0 (depressive symptoms absent) to 72 (numerically highest level of depressive symptoms).

Posted

Mean

Standard Deviation

Units on a scale

Weeks 8 (double-blind baseline) through 14

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Secondary

Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14

The Bech Melancholia is sum of scores on 6 items (items 1, 2, 7, 8, 10 and 13) pertaining to melancholia within HAM-D. The items are rated on a scale of 0-4, higher scores reflecting greater severity. Total possible score is 0-24.

Posted

Mean

Standard Deviation

Units on a scale

Weeks 8 (double-blind baseline) through 14

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Secondary

Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14

CGI-S was defined as 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill participants). Higher score = more affected.

Posted

Mean

Standard Deviation

Units on a scale

Week 8 (double-blind baseline) and weeks 9, 10, 12, 14

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Secondary

Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14

The SIS is to rate suffering with regard to irritability symptoms. The degree to which irritability interferes with work, social and family function is also queried. The total SIS score is the sum of 7 items. Each item is rated on a scale of 0-10, for a total numeric range of scores from 0 (not at all) to 70 (extremely). The SIS also records the number of days impaired by irritability.

Posted

Mean

Standard Deviation

Units on a scale

Weeks 8 (double-blind baseline), 11 and 14

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Secondary

Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14

SDS is defined as a self-administered tool that measures functional impairment including work/school, social life, and family life/home responsibilities. Items are rated on a scale of 0-10 visual analog scale (0=not at all impaired, 10=extremely impaired), for a total numeric range of scores from 0 (not at all impaired) to 30 (extremely impaired).

Posted

Mean

Standard Deviation

Units on a scale

Weeks 8 (double-blind baseline), 11 and 14

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Secondary

Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14

SDS subscale is defined as a self-administered tool that measures functional impairment in 3-item including work/school, social life, and family life/home responsibilities. Items are rated on a scale of 0-10 visual analog scale, for a total numeric range of scores from 0 (not at all impaired) to 30 (extremely impaired).

Posted

Mean

Standard Deviation

Units on a scale

Weeks 8 (double-blind baseline), 11 and 14

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Secondary

Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14

CGI-I was defined as a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.

Posted

Mean

Standard Deviation

Units on a scale

Weeks 8 (double-blind baseline) 9, 10, 12 and 14

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Secondary

Number of Participants With Remission at Weeks 9, 10, 12 and 14

Remission was defined as response plus an absolute MADRS total score of less than or equal to 10 plus a CGI-I score less than 2 ('much' or 'very much' improved).

Posted

Number

Participants

Weeks 9, 10, 12 and 14

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Secondary

Number of Participants With Response at Weeks 9 Through 14

Response was defined as greater than 50 percent reduction from double-blind baseline in MADRS total score.

Posted

Number

Participants

Weeks 9 through 14

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Secondary

Population Pharmacokinetics

Population pharmacokinetic analysis involved mixed effects modeling using nonlinear mixed effects modeling (NONMEM) software. The intent of this analysis was to establish a basic population pharmacokinetic model for CP-601,927 and to determine inter-individual and residual variability in population clearance, and volume of distribution of drug. Relationship of demographic variables (gender, age, body weight, height and ethnicity), concomitant medications and measures of altered hepatic and renal function were examined by fitting measured CP-601,927 concentrations

Data for this outcome measure was not collected and reported because the planned analysis (data collection) was not done as the study was stopped early for futility.

Not Posted

Weeks 11,12 and 14

Participants

Secondary

Plasma CP-601,927 Concentration

Blood samples were collected for plasma CP-601,927 concentration analysis which was summarized by mean and standard deviation.

All randomized participants with at least one dose of study medication in DB (double blind) phase and one valid plasma concentration measurement collected during the DB phase was be included in the analyses of the PK endpoints. Number Analyzed = number of participants with evaluable data at each timeframe.

Posted

Mean

Standard Deviation

ng/mL

Week 11, 12 and 14

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Units	Counts
Participants	OG000

Other Pre-specified

The Sheehan Suicidality Tracking Scale (STS)

The Sheehan Suicidality Tracking Scale (STS) measures treatment-emergent suicidal ideation as well as behaviors. It can be administered by a clinician or filled in by a participant. Prior to analysis, the STS was mapped to the Columbia Classification Algorithm of Suicide Assessment(C-CASA) categories, which has 9-item including completed suicide, suicide attempt, preparatory acts, suicidal ideation, self-injurious behavior, self-injurious no intent, unknown fatal,unknown non-fatal or other not deliberate. Participants who were mapped to C-CASA items were reported.

Posted

Number

Participants

Week 8 (double-blind baseline) and weeks 9 through 14

ID	Title	Description
OG000	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.
OG001	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Palpitations	Cardiac disorders	MedDRA 14.1	Non-systematic Assessment	EG0004 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Tachycardia	Cardiac disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Cerumen impaction	Ear and labyrinth disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Conjunctivitis	Eye disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Vision blurred	Eye disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Visual impairment	Eye disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0005 affected297 at risk EG0013 affected77 at risk EG0020 affected85 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0011 affected77 at risk EG0021 affected85 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0006 affected297 at risk EG0014 affected77 at risk EG0021 affected85 at risk
Abdominal tenderness	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG00011 affected297 at risk EG0012 affected77 at risk EG0023 affected85 at risk
Dental caries	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG00028 affected297 at risk EG0014 affected77 at risk EG0025 affected85 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG00017 affected297 at risk EG0014 affected77 at risk EG0028 affected85 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0006 affected297 at risk EG0013 affected77 at risk EG0021 affected85 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Eructation	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Faeces discoloured	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Flatulence	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0007 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Gastrointestinal pain	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Gastrointestinal sounds abnormal	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Gingival swelling	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG00039 affected297 at risk EG00111 affected77 at risk EG00212 affected85 at risk
Oesophageal obstruction	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Tongue cyst	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Toothache	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0010 affected77 at risk EG0022 affected85 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0012 affected77 at risk EG0021 affected85 at risk
Asthenia	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0011 affected77 at risk EG0021 affected85 at risk
Chills	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Drug withdrawal syndrome	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Fatigue	General disorders	MedDRA 14.1	Non-systematic Assessment	EG00018 affected297 at risk EG0013 affected77 at risk EG00213 affected85 at risk
Feeling abnormal	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Feeling hot	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Feeling jittery	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Influenza like illness	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Irritability	General disorders	MedDRA 14.1	Non-systematic Assessment	EG00012 affected297 at risk EG0012 affected77 at risk EG0025 affected85 at risk
Local swelling	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Oedema peripheral	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0004 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Pain	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Pyrexia	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0004 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Thirst	General disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Biliary colic	Hepatobiliary disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Hypersensitivity	Immune system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Multiple allergies	Immune system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Seasonal allergy	Immune system disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Abscess limb	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Bronchitis	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Cellulitis staphylococcal	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Conjunctivitis infective	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Fungal infection	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Gastroenteritis	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Gastrointestinal viral infection	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Gingival infection	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Herpes simplex	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Influenza	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0006 affected297 at risk EG0011 affected77 at risk EG0022 affected85 at risk
Laryngitis	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Nasopharyngitis	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG00010 affected297 at risk EG0012 affected77 at risk EG0022 affected85 at risk
Oral infection	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Pharyngitis streptococcal	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Pneumonia	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Respiratory tract infection	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Sinusitis	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0005 affected297 at risk EG0011 affected77 at risk EG0022 affected85 at risk
Tooth abscess	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Tooth infection	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG00024 affected297 at risk EG0016 affected77 at risk EG0024 affected85 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0006 affected297 at risk EG0014 affected77 at risk EG0022 affected85 at risk
Viral infection	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Vulvovaginal candidiasis	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Excoriation	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0012 affected77 at risk EG0021 affected85 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Fractured coccyx	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Fractured sacrum	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Meniscus lesion	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Alanine aminotransferase increased	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Blood glucose decreased	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Blood glucose increased	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Blood pressure increased	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0011 affected77 at risk EG0023 affected85 at risk
Colonoscopy	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Gamma-glutamyltransferase	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Liver function test abnormal	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Positive Rombergism	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Vitamin D decreased	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Weight decreased	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0012 affected77 at risk EG0020 affected85 at risk
Weight increased	Investigations	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0021 affected85 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.1	Non-systematic Assessment	EG0005 affected297 at risk EG0013 affected77 at risk EG0021 affected85 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Food craving	Metabolism and nutrition disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Increased appetite	Metabolism and nutrition disorders	MedDRA 14.1	Non-systematic Assessment	EG0004 affected297 at risk EG0011 affected77 at risk EG0023 affected85 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0011 affected77 at risk EG0022 affected85 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0011 affected77 at risk EG0025 affected85 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Muscle disorder	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0012 affected77 at risk EG0021 affected85 at risk
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Muscle twitching	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0012 affected77 at risk EG0020 affected85 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0022 affected85 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0004 affected297 at risk EG0012 affected77 at risk EG0021 affected85 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (v14.1)	Non-systematic Assessment	EG0003 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Spondylitis	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Akathisia	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Amnesia	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Aphasia	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Cognitive disorder	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Disturbance in attention	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Dizziness	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG00022 affected297 at risk EG0015 affected77 at risk EG0024 affected85 at risk
Dysgeusia	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Dyskinesia	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Headache	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG00042 affected297 at risk EG00116 affected77 at risk EG00212 affected85 at risk
Hypersomnia	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Lethargy	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0011 affected77 at risk EG0021 affected85 at risk
Memory impairment	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Migraine	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Neuralgia	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Oromandibular dystonia	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Paraesthesia	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0004 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Poor quality sleep	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Psychomotor hyperactivity	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Restless legs syndrome	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Retrograde amnesia	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Sedation	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0006 affected297 at risk EG0011 affected77 at risk EG0021 affected85 at risk
Sinus headache	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Somnolence	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG00018 affected297 at risk EG0014 affected77 at risk EG0024 affected85 at risk
Syncope	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Tension headache	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Tremor	Nervous system disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0012 affected77 at risk EG0020 affected85 at risk
Abnormal dreams	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0015 affected77 at risk EG0023 affected85 at risk
Affective disorder	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Agitation	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Anger	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Anorgasmia	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Anxiety	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0008 affected297 at risk EG0012 affected77 at risk EG0021 affected85 at risk
Apathy	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Bruxism	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Depression	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0004 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Emotional disorder	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Initial insomnia	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0011 affected77 at risk EG0021 affected85 at risk
Insomnia	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG00024 affected297 at risk EG00110 affected77 at risk EG00210 affected85 at risk
Libido decreased	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0007 affected297 at risk EG0011 affected77 at risk EG0022 affected85 at risk
Mental status changes	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Middle insomnia	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Nervousness	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Nightmare	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0013 affected77 at risk EG0022 affected85 at risk
Orgasm abnormal	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Panic attack	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Panic reaction	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Paranoia	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Personality disorder	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Restlessness	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Sleep disorder	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Sleep terror	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Suspiciousness	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Tachyphrenia	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Terminal insomnia	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Dysuria	Renal and urinary disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Micturition urgency	Renal and urinary disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Ejaculation delayed	Reproductive system and breast disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Erection increased	Reproductive system and breast disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Menstruation delayed	Reproductive system and breast disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Polycystic ovaries	Reproductive system and breast disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Polymenorrhoea	Reproductive system and breast disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0012 affected77 at risk EG0021 affected85 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0007 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Yawning	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0012 affected77 at risk EG0020 affected85 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0012 affected77 at risk EG0020 affected85 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0005 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0003 affected297 at risk EG0012 affected77 at risk EG0020 affected85 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0021 affected85 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Colon polypectomy	Surgical and medical procedures	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Flushing	Vascular disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Haematoma	Vascular disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Hot flush	Vascular disorders	MedDRA 14.1	Non-systematic Assessment	EG0004 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Hypertension	Vascular disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0013 affected77 at risk EG0020 affected85 at risk
Hypotension	Vascular disorders	MedDRA 14.1	Non-systematic Assessment	EG0002 affected297 at risk EG0012 affected77 at risk EG0020 affected85 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 14.1	Non-systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Open-Label ADT	Participants treated with 1 of 5 allowed antidepressant agents in accordance with current product labeling, targeting the following doses by the end of week 2: escitalopram (Lexapro) (10-20 mg/d), citalopram (Celexa) (20-40 mg/d), fluoxetine (Prozac, Sarafem) (20-60 mg/d), paroxetine CR (Paxil CR) (37.5-62.5 mg/d), sertraline (Zoloft) (100-200 mg/d), for up to 8 weeks in open-label phase.	3	297	210	297
EG001	CP-601,927 + ADT	Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	1	77	58	77
EG002	Placebo + ADT	Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase.	1	85	61	85

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.1	Systematic Assessment	EG0000 affected297 at risk EG0011 affected77 at risk EG0020 affected85 at risk
Suicide attempt	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG0000 affected297 at risk EG0010 affected77 at risk EG0021 affected85 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Pneumonia	Infections and infestations	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 14.1	Non-systematic Assessment	EG0001 affected297 at risk EG0010 affected77 at risk EG0020 affected85 at risk