The Effect Of Dose Titration And Dose Tapering On The Tol... | NCT00401245

The Effect Of Dose Titration And Dose Tapering On The Tol... | NCT00401245 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
A	Active Comparator	Drug: desvenlafaxine succinate sustained release
B	Active Comparator	Drug: desvenlafaxine succinate sustained release
C	Active Comparator	Drug: desvenlafaxine succinate sustained release
D	Active Comparator	Drug: desvenlafaxine succinate sustained release
E	Active Comparator	Drug: Placebo
F	Active Comparator	Drug: desvenlafaxine succinate sustained release
G	Active Comparator	Drug: desvenlafaxine succinate sustained release
H

Name	Type	Description	Arm Group Labels	Other Names
desvenlafaxine succinate sustained release	Drug	Titration 100 mg	A

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Nausea During the First 2 Weeks of Treatment	Nausea by spontaneous reports to the investigators was counted if it was reported during first 2 weeks of treatment, and it was not seen before the first dose of treatment, or if it was seen before the first dose and the symptoms got worse. If multiple incidences occurred on the same participant during the 2 weeks, only 1 incidence was counted.	Baseline up to Week 2
Discontinuation Emergent Signs and Symptoms (DESS) Total Score at the End of First Week of Tapering	DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article. The DESS total score is the sum of the number of "new symptoms" and "old (but worse) symptoms" (1) and 0 for "old and unchanged symptom", "absent", or "old symptom but improved" for a total possible range of 0 to 43. A higher score indicates more symptoms.	Week 17
DESS Total Score at End of Second Week of Tapering	DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article. The DESS total score is the sum of the number of "new symptoms" and "old (but worse) symptoms" (1) and 0 for "old and unchanged symptom", "absent", or "old symptom but improved" for a total possible range of 0 to 43. A higher score indicates more symptoms.	Week 18
DESS Total Score at 1 Week After the End of Tapering	DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article. The DESS total score is the sum of the number of "new symptoms" and "old (but worse) symptoms" (1) and 0 for "old and unchanged symptom", "absent", or "old symptom but improved" for a total possible range of 0 to 43. A higher score indicates more symptoms.	Week 19

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Other Spontaneously Reported Adverse Events (AEs) in First 2 Weeks of Treatment	Any untoward medical occurrence in a participant who received study drug was considered an AE, without regard to possibility of causal relationship.	Baseline up to Week 2
Percentage of Participants Discontinuing Treatment Due to AEs in First 2 Weeks of Treatment

Other Outcomes

Measure	Description	Time Frame
Mean Age of the Participants in Tapering Phase	Participants were re-randomized to tapering phase after OL phase.	Week 17
Gender of the Participants in Tapering Phase	Participants were re-randomized to tapering phase after OL phase.

Contacts/Locations Module

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

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		Tucson	Arizona	85710	United States
Pfizer Investigational Site

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

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	DVS 25 mg, Then 100 mg	Desvenlafaxine succinate (DVS) 25 milligram (mg) tablet taken orally daily for one week and placebo matched to 100 mg and 50 mg (double blind titration phase); then 100 mg for 15 week open label (OL) phase.
FG001	DVS 25/50 mg, Then 100 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Adverse Event		FG0003 subjects FG0012 subjects FG0025 subjects FG00312 subjects FG0040 subjects FG0050 subjects FG0060 subjects FG0070 subjects
Other		FG0000 subjects FG0010 subjects FG0021 subjects FG0030 subjects FG004
Protocol Violation		FG0000 subjects FG0010 subjects FG0020 subjects FG0031 subjects FG004
Withdrawal by Subject		FG0001 subjects FG0011 subjects FG0020 subjects FG0032 subjects FG004

Between Titration and Open Label Phase

Type	Comment	Milestone Data
STARTED		FG000122 subjects FG001118 subjects FG002118 subjects FG003107 subjects FG0040 subjects FG0050 subjects FG0060 subjects FG0070 subjects
COMPLETED		FG000122 subjects FG001116 subjects FG002118 subjects FG003105 subjects FG004
NOT COMPLETED		FG0000 subjects FG0012 subjects FG0020 subjects FG0032 subjects FG004

Type	Comment	Reasons
Did not enter the open label phase		FG0000 subjects FG0012 subjects FG0020 subjects FG003

Open Label Phase

Type	Comment	Milestone Data
STARTED		FG000122 subjects FG001116 subjects FG002118 subjects FG003105 subjects FG0040 subjects FG0050 subjects FG0060 subjects FG0070 subjects
COMPLETED		FG000101 subjects FG00181 subjects FG00295 subjects FG00384 subjects FG004
NOT COMPLETED		FG00021 subjects FG00135 subjects FG00223 subjects FG00321 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0005 subjects FG00114 subjects FG0026 subjects FG003

Double Blind Tapering Phase

Type	Comment	Milestone Data
STARTED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004101 subjects FG00594 subjects FG00687 subjects FG007102 subjects
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Arm/Group Information

ID	Title	Description
BG000	DVS 25 mg, Then 100 mg	DVS 25 mg tablet taken orally daily for one week and placebo matched to 100 mg and 50 mg (double blind titration phase); then 100 mg for 15 week OL phase.
BG001	DVS 25/50 mg, Then 100 mg	DVS 25 mg tablet taken orally for first 4 days followed by 50 mg for next 3 days for the first week and placebo matched to 100 mg (double blind titration phase); then 100 mg for 15 week OL phase.
BG002	DVS 50 mg, Then 100 mg	DVS 50 mg tablet taken orally daily for one week and placebo matched to 100 mg and 25 mg (double blind titration phase); then 100 mg for 15 week OL phase.
BG003	DVS 100 mg, Then 100 mg	DVS 100 mg tablet taken orally daily for one week and placebo matched to 25 mg and 50 mg (double blind titration phase); then 100 mg for 15 week OL phase.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00054.52± 5.01 BG00154.40± 6.37 BG00253.98± 5.16 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000126 BG001121 BG002

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

Number of Participants With Nausea During the First 2 Weeks of Treatment

Nausea by spontaneous reports to the investigators was counted if it was reported during first 2 weeks of treatment, and it was not seen before the first dose of treatment, or if it was seen before the first dose and the symptoms got worse. If multiple incidences occurred on the same participant during the 2 weeks, only 1 incidence was counted.

The titration population included all randomly assigned participants who had taken at least 1 dose of double-blind test article during the double-blind titration period.

Posted

Number

Participants

Baseline up to Week 2

ID	Title	Description
OG000	DVS 25 mg, Then 100 mg	DVS 25 mg tablet taken orally daily for one week and placebo matched to 100 mg and 50 mg (double blind titration phase); then 100 mg for 15 week OL phase.
OG001	DVS 25/50 mg, Then 100 mg	DVS 25 mg tablet taken orally for first 4 days followed by 50 mg for next 3 days for the first week and placebo matched to 100 mg (double blind titration phase); then 100 mg for 15 week OL phase.
OG002	DVS 50 mg, Then 100 mg	DVS 50 mg tablet taken orally daily for one week and placebo matched to 100 mg and 25 mg (double blind titration phase); then 100 mg for 15 week OL phase.
OG003	DVS 100 mg, Then 100 mg	DVS 100 mg tablet taken orally daily for one week and placebo matched to 25 mg and 50 mg (double blind titration phase); then 100 mg for 15 week OL phase.

Units	Counts
Participants	OG000126 OG001121 OG002124 OG003

Title

Denominators

Categories

Title	Measurements
	OG00024 OG00131 OG00228 OG003

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 OG002 OG003	Overall comparison was made between each titration regimen and the control regimen (100 mg).	Chi-squared		0.024	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.												No	Superiority or Other

Primary

Discontinuation Emergent Signs and Symptoms (DESS) Total Score at the End of First Week of Tapering

DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article. The DESS total score is the sum of the number of "new symptoms" and "old (but worse) symptoms" (1) and 0 for "old and unchanged symptom", "absent", or "old symptom but improved" for a total possible range of 0 to 43. A higher score indicates more symptoms.

The tapering population included all participants who had completed at least 6 weeks of treatment and taken at least 1 dose of double-blind test article during the tapering phase.

Posted

Mean

Standard Deviation

Units on a scale

Week 17

ID	Title	Description
OG000	DVS 50 mg QOD	Re-randomized to DVS 50 mg tablet taken orally QOD alternating with placebo matched to 50 mg QOD and placebo matched to 25 mg daily for 2 weeks (double blind tapering phase).
OG001	DVS 50/25 mg	Re-randomized to DVS 50 mg tablet taken orally daily for first week along with placebo matched to 25 mg. For further 1 week, participants received DVS 25 mg tablet orally daily and placebo matched to 50 mg (double blind tapering phase).
OG002	DVS 50 mg/Placebo

Primary

DESS Total Score at End of Second Week of Tapering

Tapering population included all participants who had completed at least 6 weeks of treatment and taken at least 1 dose of double-blind test article during the tapering phase. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure at the specified time point for each group respectively.

Posted

Mean

Standard Deviation

Units on a scale

Week 18

ID	Title	Description
OG000	DVS 50 mg QOD	Re-randomized to DVS 50 mg tablet taken orally QOD alternating with placebo matched to 50 mg QOD and placebo matched to 25 mg daily for 2 weeks (double blind tapering phase).
OG001	DVS 50/25 mg	Re-randomized to DVS 50 mg tablet taken orally daily for first week along with placebo matched to 25 mg. For further 1 week, participants received DVS 25 mg tablet orally daily and placebo matched to 50 mg (double blind tapering phase).
OG002

Primary

DESS Total Score at 1 Week After the End of Tapering

Posted

Mean

Standard Deviation

Units on a scale

Week 19

ID	Title	Description
OG000	DVS 50 mg QOD	Re-randomized to DVS 50 mg tablet taken orally QOD alternating with placebo matched to 50 mg QOD and placebo matched to 25 mg daily for 2 weeks (double blind tapering phase).
OG001	DVS 50/25 mg	Re-randomized to DVS 50 mg tablet taken orally daily for first week along with placebo matched to 25 mg. For further 1 week, participants received DVS 25 mg tablet orally daily and placebo matched to 50 mg (double blind tapering phase).
OG002

Secondary

Number of Participants With Other Spontaneously Reported Adverse Events (AEs) in First 2 Weeks of Treatment

Any untoward medical occurrence in a participant who received study drug was considered an AE, without regard to possibility of causal relationship.

The titration population included all randomly assigned participants who had taken at least 1 dose of double-blind test article during the double-blind titration period.

Posted

Number

Participants

Baseline up to Week 2

ID	Title	Description
OG000	DVS 25 mg, Then 100 mg	DVS 25 mg tablet taken orally daily for one week and placebo matched to 100 mg and 50 mg (double blind titration phase); then 100 mg for 15 week OL phase.
OG001	DVS 25/50 mg, Then 100 mg	DVS 25 mg tablet taken orally for first 4 days followed by 50 mg for next 3 days for the first week and placebo matched to 100 mg (double blind titration phase); then 100 mg for 15 week OL phase.
OG002	DVS 50 mg, Then 100 mg	DVS 50 mg tablet taken orally daily for one week and placebo matched to 100 mg and 25 mg (double blind titration phase); then 100 mg for 15 week OL phase.

Secondary

Percentage of Participants Discontinuing Treatment Due to AEs in First 2 Weeks of Treatment

Any untoward medical occurrence in a participant who received study drug was considered an AE, without regard to possibility of causal relationship.

The titration population included all randomly assigned participants who had taken at least 1 dose of double-blind test article during the double-blind titration period.

Posted

Number

Percentage of participants

Baseline up to Week 2

ID	Title	Description
OG000	DVS 25 mg, Then 100 mg	DVS 25 mg tablet taken orally daily for one week and placebo matched to 100 mg and 50 mg (double blind titration phase); then 100 mg for 15 week OL phase.
OG001	DVS 25/50 mg, Then 100 mg	DVS 25 mg tablet taken orally for first 4 days followed by 50 mg for next 3 days for the first week and placebo matched to 100 mg (double blind titration phase); then 100 mg for 15 week OL phase.
OG002	DVS 50 mg, Then 100 mg	DVS 50 mg tablet taken orally daily for one week and placebo matched to 100 mg and 25 mg (double blind titration phase); then 100 mg for 15 week OL phase.

Secondary

Number of Participants With Each DESS at the End of First Week of Tapering

DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.

The tapering population included all participants who had completed at least 6 weeks of treatment and taken at least 1 dose of double-blind test article during the tapering phase.

Posted

Number

Participants

Week 17

ID	Title	Description
OG000	DVS 50 mg QOD	Re-randomized to DVS 50 mg tablet taken orally QOD alternating with placebo matched to 50 mg QOD and placebo matched to 25 mg daily for 2 weeks (double blind tapering phase).
OG001	DVS 50/25 mg	Re-randomized to DVS 50 mg tablet taken orally daily for first week along with placebo matched to 25 mg. For further 1 week, participants received DVS 25 mg tablet orally daily and placebo matched to 50 mg (double blind tapering phase).
OG002	DVS 50 mg/Placebo	Re-randomized to DVS 50 mg tablet taken orally daily for first week and placebo matched to 25 mg. For further 1 week, participants received placebo matched to 25 mg and 50 mg (double blind tapering phase).

Secondary

Number of Participants With Each DESS at the End of Second Week of Tapering

DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.

Posted

Number

Participants

Week 18

ID	Title	Description
OG000	DVS 50 mg QOD	Re-randomized to DVS 50 mg tablet taken orally QOD alternating with placebo matched to 50 mg QOD and placebo matched to 25 mg daily for 2 weeks (double blind tapering phase).
OG001	DVS 50/25 mg	Re-randomized to DVS 50 mg tablet taken orally daily for first week along with placebo matched to 25 mg. For further 1 week, participants received DVS 25 mg tablet orally daily and placebo matched to 50 mg (double blind tapering phase).
OG002	DVS 50 mg/Placebo	Re-randomized to DVS 50 mg tablet taken orally daily for first week and placebo matched to 25 mg. For further 1 week, participants received placebo matched to 25 mg and 50 mg (double blind tapering phase).

Secondary

Number of Participants With Each DESS One Week After End of Tapering

DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article.

Posted

Number

Participants

Week 19

ID	Title	Description
OG000	DVS 50 mg QOD	Re-randomized to DVS 50 mg tablet taken orally QOD alternating with placebo matched to 50 mg QOD and placebo matched to 25 mg daily for 2 weeks (double blind tapering phase).
OG001	DVS 50/25 mg	Re-randomized to DVS 50 mg tablet taken orally daily for first week along with placebo matched to 25 mg. For further 1 week, participants received DVS 25 mg tablet orally daily and placebo matched to 50 mg (double blind tapering phase).
OG002	DVS 50 mg/Placebo	Re-randomized to DVS 50 mg tablet taken orally daily for first week and placebo matched to 25 mg. For further 1 week, participants received placebo matched to 25 mg and 50 mg (double blind tapering phase).

Secondary

Number of Participants Showing Satisfaction With Tolerability During the First Two Weeks of Treatment

Satisfaction with tolerability (lack of bothersomeness) was assessed using a questionnaire via an interactive voice response system (IVRS)/interactive web based response system (IWRS), and evaluated based on participants' response of extremely satisfied, satisfied, neutral, dissatisfied or extremely dissatisfied with the study medication.

The titration population included all randomly assigned participants who had taken at least 1 dose of double-blind test article during the double-blind titration period. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the time points for each group respectively.

Posted

Number

Participants

Week 1 and Week 2

ID	Title	Description
OG000	DVS 25 mg, Then 100 mg	DVS 25 mg tablet taken orally daily for one week and placebo matched to 100 mg and 50 mg (double blind titration phase); then 100 mg for 15 week OL phase.
OG001	DVS 25/50 mg, Then 100 mg	DVS 25 mg tablet taken orally for first 4 days followed by 50 mg for next 3 days for the first week and placebo matched to 100 mg (double blind titration phase); then 100 mg for 15 week OL phase.
OG002	DVS 50 mg, Then 100 mg

Secondary

Number of Participants Showing Satisfaction With Tolerability at the End of Tapering

Satisfaction with tolerability (lack of bothersomeness) was assessed using a questionnaire via an IVRS/IWRS and evaluated based on participants' response of extremely satisfied, satisfied, neutral, dissatisfied or extremely dissatisfied with the study medication.

Posted

Number

Participants

Week 19

ID	Title	Description
OG000	DVS 50 mg QOD	Re-randomized to DVS 50 mg tablet taken orally QOD alternating with placebo matched to 50 mg QOD and placebo matched to 25 mg daily for 2 weeks (double blind tapering phase).
OG001	DVS 50/25 mg	Re-randomized to DVS 50 mg tablet taken orally daily for first week along with placebo matched to 25 mg. For further 1 week, participants received DVS 25 mg tablet orally daily and placebo matched to 50 mg (double blind tapering phase).
OG002	DVS 50 mg/Placebo

Secondary

Menopause Symptoms-treatment Satisfaction Questionnaire (MS-TSQ) Score

MS-TSQ is a questionnaire assessing participants' degree of satisfaction with regard to the test article which was administered to the participants via an IVRS/IWRS. The questionnaire comprised 8 questions and each was rated on a scale from 0 (extremely dissatisfied) to 4 (extremely satisfied).

The OL population included all participants who had taken at least 1 dose of open label test article. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure at the specified time point for each group respectively.

Posted

Mean

Standard Deviation

Units on a scale

Week 16

ID	Title	Description
OG000	DVS 100 mg	DVS 100 mg tablet taken orally daily for 15 weeks (OL phase).

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Menopause-specific Quality of Life Questionnaire (MenQOL) Score at Week 4, Week 8, Week 12 and Week 16

MenQOL questionnaire assessed how bothered participants were with 31 symptoms. It contains domains: vasomotor (items 1-3); psychosocial (items 4-10); physical (items 11-26); sexual (items 27-29); in addition to nausea and indigestion. 31 individual symptoms are rated on a scale of 0 (not at all bothered) to 6 (extremely bothered). Total possible score ranged from 0 to 186. MenQOL summary score was calculated as mean of four domain scores (Physical function, Psychosocial function, Sexual function and Vasomotor function) ranging from 1 to 8, with higher scores indicating worse quality of life.

The OL population included all participants who had taken at least 1 dose of open label test article. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the time points for each group respectively.

Posted

Mean

Standard Deviation

Units on a scale

Baseline, Week 4, Week 8, Week 12 and Week 16

ID	Title	Description
OG000	DVS 100 mg	DVS 100 mg tablet taken orally daily for 15 weeks (OL phase).

Units	Counts
Participants

Other Pre-specified

Mean Age of the Participants in Tapering Phase

Participants were re-randomized to tapering phase after OL phase.

The tapering population included all participants who had completed at least 6 weeks of treatment and taken at least 1 dose of double-blind test article during the tapering phase.

Posted

Mean

Standard Deviation

Years

Week 17

ID	Title	Description
OG000	DVS 50 mg QOD	Re-randomized to DVS 50 mg tablet taken orally QOD alternating with placebo matched to 50 mg QOD and placebo matched to 25 mg daily for 2 weeks (double blind tapering phase).
OG001	DVS 50/25 mg	Re-randomized to DVS 50 mg tablet taken orally daily for first week along with placebo matched to 25 mg. For further 1 week, participants received DVS 25 mg tablet orally daily and placebo matched to 50 mg (double blind tapering phase).
OG002	DVS 50 mg/Placebo	Re-randomized to DVS 50 mg tablet taken orally daily for first week and placebo matched to 25 mg. For further 1 week, participants received placebo matched to 25 mg and 50 mg (double blind tapering phase).
OG003

Other Pre-specified

Gender of the Participants in Tapering Phase

Participants were re-randomized to tapering phase after OL phase.

The tapering population included all participants who had completed at least 6 weeks of treatment and taken at least 1 dose of double-blind test article during the tapering phase.

Posted

Number

Participants

Week 17

ID	Title	Description
OG000	DVS 50 mg QOD	Re-randomized to DVS 50 mg tablet taken orally QOD alternating with placebo matched to 50 mg QOD and placebo matched to 25 mg daily for 2 weeks (double blind tapering phase).
OG001	DVS 50/25 mg	Re-randomized to DVS 50 mg tablet taken orally daily for first week along with placebo matched to 25 mg. For further 1 week, participants received DVS 25 mg tablet orally daily and placebo matched to 50 mg (double blind tapering phase).
OG002	DVS 50 mg/Placebo	Re-randomized to DVS 50 mg tablet taken orally daily for first week and placebo matched to 25 mg. For further 1 week, participants received placebo matched to 25 mg and 50 mg (double blind tapering phase).
OG003

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	DVS 25 mg (Titration Phase)	DVS 25 mg tablet taken orally daily for one week and placebo matched to 100 mg and 50 mg (double blind titration phase).	0	126	50	126
EG001	DVS 25/50 mg (Titration Phase)	DVS 25 mg tablet taken orally for first 4 days followed by 50 mg for next 3 days for the first week and placebo matched to 100 mg (double blind titration phase).	0	121	55	121
EG002	DVS 50 mg (Titration Phase)	DVS 50 mg tablet taken orally daily for one week and placebo matched to 100 mg and 25 mg (double blind titration phase).	0	124	57	124
EG003	DVS 100 mg (Titration Phase)	DVS 100 mg tablet taken orally daily for one week and placebo matched to 25 mg and 50 mg (double blind titration phase).	0	122	73	122
EG004	DVS 100 mg (OL Phase)	After 1 week of double blind titration phase, DVS 100 mg tablet taken orally daily for 15 weeks.	3	461	340	461
EG005	DVS 50 mg QOD (Tapering Phase)	Re-randomized to DVS 50 mg tablet taken orally QOD alternating with placebo matched to 50 mg QOD and placebo matched to 25 mg daily for 2 weeks (double blind tapering phase).	0	101	74	101
EG006	DVS 50/25 mg (Tapering Phase)	Re-randomized to DVS 50 mg tablet taken orally daily for first week along with placebo matched to 25 mg. For further 1 week, participants received DVS 25 mg tablet orally daily and placebo matched to 50 mg (double blind tapering phase).	0	94	64	94
EG007	DVS 50 mg/Placebo (Tapering Phase)	Re-randomized to DVS 50 mg tablet taken orally daily for first week and placebo matched to 25 mg. For further 1 week, participants received placebo matched to 25 mg and 50 mg (double blind tapering phase).	0	87	67	87
EG008	Placebo (Tapering Phase)	Re-randomized to placebo tablets matched to 25 mg and 50 mg taken orally daily for two weeks (double blind tapering phase).	1	102	79	102

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chest pain	General disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG0030 affected122 at risk EG0041 affected461 at risk EG0050 affected101 at risk EG0060 affected94 at risk EG0070 affected87 at risk EG0080 affected102 at risk
Pericarditis	Cardiac disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Supraventricular tachycardia	Cardiac disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Pneumonia	Respiratory, thoracic and mediastinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0001 affected126 at risk EG0014 affected121 at risk EG0021 affected124 at risk EG0032 affected122 at risk EG00420 affected461 at risk EG0056 affected101 at risk EG0063 affected94 at risk EG0071 affected87 at risk EG0085 affected102 at risk
Accidental injury	Injury, poisoning and procedural complications	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Asthenia	General disorders	COSTART	Non-systematic Assessment	EG0006 affected126 at risk EG0014 affected121 at risk EG00212 affected121 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Chills	General disorders	COSTART	Non-systematic Assessment	EG0001 affected126 at risk EG0010 affected121 at risk EG0022 affected124 at risk EG003
Cyst	General disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Fever	General disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Flu syndrome	General disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Headache	Nervous system disorders	COSTART	Non-systematic Assessment	EG00015 affected126 at risk EG00112 affected121 at risk EG00214 affected124 at risk EG003
Infection	Infections and infestations	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Pain	Musculoskeletal and connective tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Hypertension	Vascular disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Migraine	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Palpitation	Cardiac disorders	COSTART	Non-systematic Assessment	EG0001 affected126 at risk EG0011 affected121 at risk EG0021 affected124 at risk EG003
Vasodilatation	Vascular disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Abdominal distension	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Anorexia	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0001 affected126 at risk EG0012 affected121 at risk EG0025 affected124 at risk EG003
Constipation	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0002 affected126 at risk EG0015 affected121 at risk EG0024 affected124 at risk EG003
Diarrhea	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0003 affected126 at risk EG0014 affected121 at risk EG0021 affected124 at risk EG003
Dry mouth	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0004 affected126 at risk EG0019 affected121 at risk EG00211 affected124 at risk EG003
Dyspepsia	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0004 affected126 at risk EG0012 affected121 at risk EG0023 affected124 at risk EG003
Flatulence	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Gastroesophageal reflux disease	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Increased appetite	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Increased salivation	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Nausea	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG00019 affected126 at risk EG00126 affected121 at risk EG00226 affected124 at risk EG003
Vomiting	Gastrointestinal disorders	COSTART	Non-systematic Assessment	EG0001 affected126 at risk EG0011 affected121 at risk EG0023 affected124 at risk EG003
Anemia	Blood and lymphatic system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Echymosis	Blood and lymphatic system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Hypercholesteremia	Metabolism and nutrition disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Hyperlipemia	Metabolism and nutrition disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Leg cramps	Musculoskeletal and connective tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Muscle cramp	Musculoskeletal and connective tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Abnormal dreams	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Agitation	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Anxiety	Nervous system disorders	COSTART	Non-systematic Assessment	EG0002 affected126 at risk EG0014 affected121 at risk EG0021 affected124 at risk EG003
Confusion	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Depersonalization	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Dizziness	Nervous system disorders	COSTART	Non-systematic Assessment	EG0002 affected126 at risk EG0016 affected121 at risk EG0025 affected124 at risk EG003
Emotional lability	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Euphoria	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Hostility	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Hypesthesia	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Incoordination	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Insonmnia	Nervous system disorders	COSTART	Non-systematic Assessment	EG0003 affected126 at risk EG0017 affected121 at risk EG0027 affected124 at risk EG003
Libido decreased	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Memory impairement	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Nervousness	Nervous system disorders	COSTART	Non-systematic Assessment	EG0002 affected126 at risk EG0013 affected121 at risk EG0020 affected124 at risk EG003
Paresthesia	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Restless legs syndrome	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Somnolence	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0012 affected121 at risk EG0027 affected124 at risk EG003
Speech disorder	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Thinking abnormal	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Tremor	Nervous system disorders	COSTART	Non-systematic Assessment	EG0001 affected126 at risk EG0012 affected121 at risk EG0023 affected124 at risk EG003
Vertigo	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Cough increased	Respiratory, thoracic and mediastinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Pharyngitis	Respiratory, thoracic and mediastinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Rhinitis	Respiratory, thoracic and mediastinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Sinusitis	Respiratory, thoracic and mediastinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Upper respiratory infection	Respiratory, thoracic and mediastinal disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Rash	Skin and subcutaneous tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Sweating	Skin and subcutaneous tissue disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Abnormal vision	Eye disorders	COSTART	Non-systematic Assessment	EG0001 affected126 at risk EG0011 affected121 at risk EG0022 affected124 at risk EG003
Eye pain	Eye disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Parosmia	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Taste perversion	Nervous system disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Tinnitus	Ear and labyrinth disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Abnormal ejaculation /orgasm	Reproductive system and breast disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Urine abnormality	Renal and urinary disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Uterine hemorrhage	Reproductive system and breast disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003
Reaction unevaluable	General disorders	COSTART	Non-systematic Assessment	EG0000 affected126 at risk EG0010 affected121 at risk EG0020 affected124 at risk EG003

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG003	For DVS 50 mg QOD, analysis of variance (ANOVA) was used to compare the DESS score between each tapering regimen and the control regimen (no tapering) for the titration population, where treatment was kept as the factor.	ANOVA	< 0.001	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.	No	Superiority or Other
OG001 OG003	For DVS 50/25 mg, ANOVA was used to compare the DESS score between each tapering regimen and the control regimen (no tapering) for the titration population, where treatment was kept as the factor.	ANOVA	<0.001	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.	No	Superiority or Other
OG002 OG003	For DVS 50 mg/Placebo, ANOVA was used to compare the DESS score between each tapering regimen and the control regimen (no tapering) for the titration population, where treatment was kept as the factor.	ANOVA	<0.001	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.	No	Superiority or Other

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG003	For DVS 50 mg QOD, ANOVA was used to compare the DESS score between each tapering regimen and the control regimen (no tapering) for the titration population, where treatment was kept as the factor	ANOVA	0.092	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.	No	Superiority or Other
OG001 OG003	For DVS 50/25 mg, ANOVA was used to compare the DESS score between each tapering regimen and the control regimen (no tapering) for the titration population, where treatment was kept as the factor	ANOVA	0.997	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.	No	Superiority or Other
OG002 OG003	For DVS 50 mg/Placebo, ANOVA was used to compare the DESS score between each tapering regimen and the control regimen (no tapering) for the titration population, where treatment was kept as the factor	ANOVA	0.009	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.	No	Superiority or Other

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Confidence Interval Sides	Confidence Interval %	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG003	For DVS 50 mg QOD, ANOVA was used to compare the DESS score between each tapering regimen and the control regimen (no tapering) for the titration population, where treatment was kept as the factor.	ANOVA	0.078	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.	2-Sided		No	Superiority or Other
OG001 OG003	For DVS 50/25 mg, ANOVA was used to compare the DESS score between each tapering regimen and the control regimen (no tapering) for the titration population, where treatment was kept as the factor.	ANOVA	0.005	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.		95	No	Superiority or Other
OG002 OG003	For DVS 50mg/Placebo, ANOVA was used to compare the DESS score between each tapering regimen and the control regimen (no tapering) for the titration population, where treatment was kept as the factor.	ANOVA	0.929	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.		95	No	Superiority or Other

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 OG002 OG003	Overall comparison was made between each titration regimen and the control regimen (100 mg).	Chi-squared		0.017	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.												No	Superiority or Other

Title

Denominators

Categories

Agitation

Title	Measurements
	OG0001 OG0017 OG0026 OG00318

Blurred vision

Title	Measurements
	OG0004 OG0014 OG0022 OG003

Bouts of crying or tearfulness

Title	Measurements
	OG0005 OG0013 OG0026 OG003

Burning, numbness, tingling sensations

Title	Measurements
	OG0005 OG0013 OG0023 OG003

Chills

Title	Measurements
	OG0003 OG0012 OG0023 OG003

Confusion or trouble concentrating

Title	Measurements
	OG0005 OG0014 OG0022 OG003

Diarrhea

Title	Measurements
	OG0007 OG0013 OG0024 OG003

Dizziness, lightheadedness, sensation of spinning

Title	Measurements
	OG00018 OG0017 OG0029 OG003

Elevated mood, feeling high

Title	Measurements
	OG0001 OG0010 OG0020 OG003

Fatigue, tiredness

Title	Measurements
	OG0009 OG00111 OG0026 OG003

Feeling unreal or detached

Title	Measurements
	OG0006 OG0012 OG0021 OG003

Fever

Title	Measurements
	OG0002 OG0010 OG0021 OG003

Forgetfulness or problems with memory

Title	Measurements
	OG0006 OG0016 OG0023 OG003

Headaches

Title	Measurements
	OG0008 OG0015 OG0029 OG003

Increased dreaming or nightmares

Title	Measurements
	OG00014 OG00113 OG00212 OG003

Increased saliva in mouth

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Irritability

Title	Measurements
	OG0006 OG0016 OG0026 OG003

Mood swings

Title	Measurements
	OG0004 OG0015 OG0024 OG003

Muscle aches or pains

Title	Measurements
	OG0005 OG0018 OG0023 OG003

Muscle cramps, spasms, or twitching

Title	Measurements
	OG0005 OG0016 OG0022 OG003

Muscle tension or stiffness

Title	Measurements
	OG0006 OG0016 OG0027 OG003

Nausea

Title	Measurements
	OG00014 OG0017 OG0025 OG003

Nervousness or anxiety

Title	Measurements
	OG0002 OG0015 OG0027 OG003

Nose running

Title	Measurements
	OG0003 OG0013 OG0023 OG003

Problems with speech or speaking clearly

Title	Measurements
	OG0003 OG0012 OG0020 OG003

Restless feeling in legs

Title	Measurements
	OG0005 OG0014 OG0020 OG003

Ringing or noises in the ears

Title	Measurements
	OG0006 OG0012 OG0026 OG003

Shaking, trembling

Title	Measurements
	OG0004 OG0014 OG0022 OG003

Shortness of breath, gasping for air

Title	Measurements
	OG0001 OG0013 OG0021 OG003

Sore eyes

Title	Measurements
	OG0003 OG0013 OG0025 OG003

Stomach bloating

Title	Measurements
	OG0005 OG0016 OG0025 OG003

Stomach cramps

Title	Measurements
	OG0006 OG0014 OG0020 OG003

Sudden outbursts of anger

Title	Measurements
	OG0003 OG0014 OG0022 OG003

Sudden panic or anxiety attacks

Title	Measurements
	OG0000 OG0012 OG0020 OG003

Sudden worsening of mood

Title	Measurements
	OG0003 OG0016 OG0024 OG003

Sweating more than usual

Title	Measurements
	OG00023 OG00119 OG00214 OG003

Trouble sleeping, insomnia

Title	Measurements
	OG00013 OG00111 OG0028 OG003

Uncontrolled mouth/tongue movements

Title	Measurements
	OG0001 OG0011 OG0020 OG003

Unsteady gait or incoordination

Title	Measurements
	OG0004 OG0011 OG0020 OG003

Unusual sensitivity to sound

Title	Measurements
	OG0001 OG0015 OG0021 OG003

Unusual tastes or smells

Title	Measurements
	OG0001 OG0012 OG0021 OG003

Unusual visual sensations

Title	Measurements
	OG0001 OG0010 OG0020 OG003

Vomiting

Title	Measurements
	OG0004 OG0011 OG0020 OG003

Title

Denominators

Categories

Agitation

Title	Measurements
	OG0006 OG0014 OG00210 OG0039

Blurred vision

Title	Measurements
	OG0002 OG0016 OG0027 OG003

Bouts of crying or tearfulness

Title	Measurements
	OG0002 OG0015 OG00218 OG003

Burning, numbness, tingling sensations

Title	Measurements
	OG0000 OG0012 OG0023 OG003

Chills

Title	Measurements
	OG0001 OG0013 OG0028 OG003

Confusion or trouble concentrating

Title	Measurements
	OG0000 OG0017 OG00211 OG003

Diarrhea

Title	Measurements
	OG0002 OG0012 OG0025 OG003

Dizziness, lightheadedness, sensation of spinning

Title	Measurements
	OG0002 OG00112 OG00221 OG003

Elevated mood, feeling high

Title	Measurements
	OG0003 OG0013 OG0025 OG003

Fatigue, tiredness

Title	Measurements
	OG0003 OG00112 OG00214 OG003

Feeling unreal or detached

Title	Measurements
	OG0000 OG0015 OG0029 OG003

Fever

Title	Measurements
	OG0000 OG0010 OG0021 OG003

Forgetfulness or problems with memory

Title	Measurements
	OG0001 OG0016 OG0024 OG003

Headaches

Title	Measurements
	OG0004 OG0015 OG0028 OG003

Increased dreaming or nightmares

Title	Measurements
	OG0004 OG0015 OG00210 OG003

Increased saliva in mouth

Title	Measurements
	OG0001 OG0011 OG0022 OG003

Irritability

Title	Measurements
	OG0005 OG00110 OG00218 OG003

Mood swings

Title	Measurements
	OG0003 OG0017 OG00214 OG003

Muscle aches or pains

Title	Measurements
	OG0002 OG0018 OG0029 OG003

Muscle cramps, spasms, or twitching

Title	Measurements
	OG0007 OG0013 OG0026 OG003

Muscle tension or stiffness

Title	Measurements
	OG0001 OG0018 OG0027 OG003

Nausea

Title	Measurements
	OG0003 OG0016 OG00215 OG003

Nervousness or anxiety

Title	Measurements
	OG0004 OG0016 OG00212 OG003

Nose running

Title	Measurements
	OG0001 OG0015 OG0024 OG003

Problems with speech or speaking clearly

Title	Measurements
	OG0000 OG0013 OG0024 OG003

Restless feeling in legs

Title	Measurements
	OG0004 OG0014 OG0024 OG003

Ringing or noises in the ears

Title	Measurements
	OG0001 OG0014 OG0026 OG003

Shaking, trembling

Title	Measurements
	OG0001 OG0013 OG0023 OG003

Shortness of breath, gasping for air

Title	Measurements
	OG0000 OG0012 OG0021 OG003

Sore eyes

Title	Measurements
	OG0002 OG0014 OG0023 OG003

Stomach bloating

Title	Measurements
	OG0001 OG0015 OG0026 OG003

Stomach cramps

Title	Measurements
	OG0002 OG0013 OG0024 OG003

Sudden outbursts of anger

Title	Measurements
	OG0004 OG0015 OG00212 OG003

Sudden panic or anxiety attacks

Title	Measurements
	OG0000 OG0013 OG0025 OG003

Sudden worsening of mood

Title	Measurements
	OG0006 OG0015 OG00218 OG003

Sweating more than usual

Title	Measurements
	OG00019 OG00117 OG00223 OG003

Trouble sleeping, insomnia

Title	Measurements
	OG0008 OG0019 OG00222 OG003

Uncontrolled mouth/tongue movements

Title	Measurements
	OG0000 OG0011 OG0020 OG003

Unsteady gait or incoordination

Title	Measurements
	OG0000 OG0017 OG0025 OG003

Unusual sensitivity to sound

Title	Measurements
	OG0000 OG0015 OG0023 OG003

Unusual tastes or smells

Title	Measurements
	OG0001 OG0011 OG0024 OG003

Unusual visual sensations

Title	Measurements
	OG0000 OG0010 OG0023 OG003

Vomiting

Title	Measurements
	OG0000 OG0010 OG0025 OG003

Title

Denominators

Categories

Agitation

Title	Measurements
	OG0006 OG0014 OG0026 OG0035

Blurred vision

Title	Measurements
	OG0002 OG0010 OG0020 OG003

Bouts of crying or tearfulness

Title	Measurements
	OG0007 OG0017 OG0022 OG003

Burning, numbness, tingling sensations

Title	Measurements
	OG0002 OG0019 OG0020 OG003

Chills

Title	Measurements
	OG0003 OG0013 OG0021 OG003

Confusion or trouble concentrating

Title	Measurements
	OG0006 OG0017 OG0024 OG003

Diarrhea

Title	Measurements
	OG0003 OG0013 OG0021 OG003

Dizziness, lightheadedness, sensation of spinning

Title	Measurements
	OG00013 OG00117 OG0022 OG003

Elevated mood, feeling high

Title	Measurements
	OG0001 OG0012 OG0020 OG003

Fatigue, tiredness

Title	Measurements
	OG0009 OG00110 OG0022 OG003

Feeling unreal or detached

Title	Measurements
	OG0006 OG0015 OG0021 OG003

Fever

Title	Measurements
	OG0002 OG0010 OG0020 OG003

Forgetfulness or problems with memory

Title	Measurements
	OG0005 OG0013 OG0022 OG003

Headaches

Title	Measurements
	OG0004 OG00111 OG0023 OG003

Increased dreaming or nightmares

Title	Measurements
	OG0007 OG00110 OG0020 OG003

Increased saliva in mouth

Title	Measurements
	OG0000 OG0011 OG0021 OG003

Irritability

Title	Measurements
	OG00011 OG0019 OG0027 OG003

Mood swings

Title	Measurements
	OG0004 OG0015 OG0026 OG003

Muscle aches or pains

Title	Measurements
	OG0005 OG0018 OG0025 OG003

Muscle cramps, spasms, or twitching

Title	Measurements
	OG0005 OG0015 OG0021 OG003

Muscle tension or stiffness

Title	Measurements
	OG0005 OG0019 OG0023 OG003

Nausea

Title	Measurements
	OG0005 OG0015 OG0020 OG003

Nervousness or anxiety

Title	Measurements
	OG0009 OG00110 OG0025 OG003

Nose running

Title	Measurements
	OG0001 OG0012 OG0023 OG003

Problems with speech or speaking clearly

Title	Measurements
	OG0000 OG0012 OG0020 OG003

Restless feeling in legs

Title	Measurements
	OG0001 OG0016 OG0023 OG003

Ringing or noises in the ears

Title	Measurements
	OG0003 OG0018 OG0020 OG003

Shaking, trembling

Title	Measurements
	OG0003 OG0013 OG0020 OG003

Shortness of breath, gasping for air

Title	Measurements
	OG0001 OG0011 OG0021 OG003

Sore eyes

Title	Measurements
	OG0003 OG0014 OG0021 OG003

Stomach bloating

Title	Measurements
	OG0003 OG0014 OG0021 OG003

Stomach cramps

Title	Measurements
	OG0002 OG0013 OG0020 OG003

Sudden outbursts of anger

Title	Measurements
	OG0004 OG0013 OG0023 OG003

Sudden panic or anxiety attacks

Title	Measurements
	OG0001 OG0015 OG0022 OG003

Sudden worsening of mood

Title	Measurements
	OG0007 OG0014 OG0025 OG003

Sweating more than usual

Title	Measurements
	OG00021 OG00119 OG0024 OG003

Trouble sleeping, insomnia

Title	Measurements
	OG00012 OG00113 OG0025 OG003

Uncontrolled mouth/tongue movements

Title	Measurements
	OG0000 OG0011 OG0020 OG003

Unsteady gait or incoordination

Title	Measurements
	OG0004 OG0015 OG0020 OG003

Unusual sensitivity to sound

Title	Measurements
	OG0001 OG0012 OG0020 OG003

Unusual tastes or smells

Title	Measurements
	OG0001 OG0013 OG0020 OG003

Unusual visual sensations

Title	Measurements
	OG0000 OG0013 OG0020 OG003

Vomiting

Title	Measurements
	OG0001 OG0010 OG0020 OG003

Title

Denominators

Categories

Week 1: Extremely dissatisfied (n=124,119,120,111)

Title	Measurements
	OG0002 OG0013 OG0021 OG0034

Week 1: Dissatisfied (n=124,119,120,111)

Title	Measurements
	OG0001 OG0016 OG0028 OG003

Week 1: Neutral (n=124,119,120,111)

Title	Measurements
	OG00020 OG00113 OG00228 OG003

Week 1: Satisfied (n=124,119,120,111)

Title	Measurements
	OG00047 OG00148 OG00243 OG003

Week 1: Extremely satisfied (n=124,119,120,111)

Title	Measurements
	OG00054 OG00149 OG00240 OG003

Week 2: Extremely dissatisfied (n=115,105,113,94)

Title	Measurements
	OG0002 OG0010 OG0020 OG003

Week 2: Dissatisfied (n=115,105,113,94)

Title	Measurements
	OG0003 OG0014 OG0028 OG003

Week 2: Neutral (n=115,105,113,94)

Title	Measurements
	OG00017 OG00117 OG00218 OG003

Week 2: Satisfied (n=115,105,113,94)

Title	Measurements
	OG00043 OG00135 OG00241 OG003

Week 2: Extremely satisfied (n=115,105,113,94)

Title	Measurements
	OG00050 OG00149 OG00246 OG003

Title

Denominators

Categories

Extremely dissatisfied

Title	Measurements
	OG0007 OG0015 OG0023 OG0036

Dissatisfied

Title	Measurements
	OG00010 OG0017 OG0023 OG003

Neutral

Title	Measurements
	OG00010 OG0015 OG0025 OG003

Satisfied

Title	Measurements
	OG00016 OG00123 OG00219 OG003

Extremely satisfied

Title	Measurements
	OG00010 OG00112 OG00210 OG003

Title

Denominators

Categories

Ability to control hot flushes during the day

Title	Measurements
	OG0002.64± 1.19

Ability to control hot flushes during the night

Title	Measurements
	OG0002.71± 1.26

Effect on quality of sleep

Title	Measurements
	OG0002.59± 1.18

Effect on mood or emotions

Title	Measurements
	OG0003.02± 0.86

Effect on interest in sex

Title	Measurements
	OG0002.37± 1.00

Effect on ability to concentrate

Title	Measurements
	OG0002.67± 0.84

Tolerability to side effects

Title	Measurements
	OG0003.04± 0.94

Overall satisfaction

Title	Measurements
	OG0002.81± 1.10

Title

Denominators

Categories

Baseline

Title	Measurements
	OG0004.46± 1.20

Week 4 (n=385)

Title	Measurements
	OG0002.99± 1.09

Week 8 (n=364)

Title	Measurements
	OG0002.85± 1.08

Week 12 (n=354)

Title	Measurements
	OG0002.76± 1.06

Week 16 (n=277)

Title	Measurements
	OG0002.67± 1.17

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Tested Non-Inferiority	Non-Inferiority Type
OG000	Comparison was made between the difference in the means from the baseline value and post-baseline (Week 4) value with 0.	t-test, 2 sided	<0.001	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.	No	Superiority or Other
OG000	Comparison was made between the difference in the means from the baseline value and post-baseline (Week 8) value with 0.	t-test, 2 sided	< 0.001	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.	No	Superiority or Other
OG000	Comparison was made between the difference in the means from the base value and post-baseline (Week 12) value with 0.	t-test, 2 sided	<0.001	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.	No	Superiority or Other
OG000	Comparison was made between the difference in the means from the baseline value and post-baseline (Week 16) value with 0.	t-test, 2 sided	<0.001	The analysis was done at a significance level of alpha = 0.05, 2-sided, without any adjustments for multiple comparisons.	No	Superiority or Other