Adjunctive Ziprasidone in the Treatment of Bipolar I Depr... | NCT00483548

Adjunctive Ziprasidone in the Treatment of Bipolar I Depr... | NCT00483548 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Ziprasidone	Experimental	Active treatment, double-blind, randomized treatment arm	Drug: Ziprasidone
Placebo	Placebo Comparator	Inactive, placebo treatment, double-blind, randomized arm	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Ziprasidone	Drug	Oral capsule formulation to be administered every day for duration of patient's participation in the trial - 40 mg on Day 1; 40 mg twice a day (BID) on Day 2; Flexible BID dosing of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg or 160 mg total daily dose from Day 3 through Week 6. Dose increases of up to 40 mg/day can occur after subject has received previous lower dose for at least 1 day.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms). Change calculated as a difference between post-baseline observation and baseline MADRS score values.	Baseline, Week 6

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 6 in Clinical Global Impression - Severity Scale (CGI-Severity or CGI-S)	CGI-S is a single-item clinician rated scale used to assess global severity of bipolar illness based on an overall evaluation of symptoms of bipolar mania, associated behavioral symptoms, and condition of the subject. Scored from 1 (normal, not at all ill) to 7 (among the most severely ill subjects). Higher score = more affected. Change calculated as a difference between post-baseline observation and baseline CGI-S score values.

Other Outcomes

Measure	Description	Time Frame
Change From Baseline in Simpson Angus Scale (SAS) Score	SAS is a clinician rated 10-item scale to measure extrapyramidal side effects (Parkinsonism or Parkinsonian side effects induced with antipsychotics); rated on a 5-point scale with range 0 (absence of condition) to 4 (presence of condition in extreme form). Global score is sum of all scores divided by the total number of items. Change calculated as a difference between post-baseline observation and baseline SAS score values.

Contacts/Locations Module

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

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		Chandler	Arizona	85226	United States
Pfizer Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
21672493	Derived	Sachs GS, Ice KS, Chappell PB, Schwartz JH, Gurtovaya O, Vanderburg DG, Kasuba B. Efficacy and safety of adjunctive oral ziprasidone for acute treatment of depression in patients with bipolar I disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011 Oct;72(10):1413-22. doi: 10.4088/JCP.09m05934.

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	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Randomized; not treated with study drug		FG0001 subjects FG0013 subjects
Adverse Event		FG00025 subjects FG00114 subjects
Laboratory abnormality		FG0001 subjects FG0012 subjects
Lack of Efficacy		FG0004 subjects FG0018 subjects
Protocol Violation		FG00011 subjects FG0017 subjects
Pregnancy		FG0001 subjects FG0010 subjects
Protocol required discontinuation		FG0006 subjects FG0016 subjects
Unable to comply with protocol schedule		FG0001 subjects FG0010 subjects
Non-compliance with medication		FG0002 subjects FG0010 subjects
Lost to Follow-up		FG0003 subjects FG0014 subjects
Withdrawal by Subject		FG0005 subjects FG0012 subjects

Arm/Group Information

ID	Title	Description
BG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
BG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
BG002	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, Customized

Number

participants

Title

Denominators

Categories

Between 18 and 65 years

Title	Measurements
	BG000147 BG001146 BG002293

>65 years

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00089 BG00191 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

Change From Baseline to Week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms). Change calculated as a difference between post-baseline observation and baseline MADRS score values.

Intent to Treat analysis set (ITT): all randomized subjects who received at least 1 dose of double-blind treatment and had at least 1 post-baseline primary efficacy evaluation.

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Units	Counts
Participants	OG000145 OG001145

Title

Denominators

Categories

Title	Measurements
	OG000-14.7± 10.7 OG001-13.2± 10.4

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	N=141 per arm (282 total) needed for 85% power for 2-sided alpha=0.05 based on true mean difference=4.0 and standard deviation (SD)=11.0 for primary endpoint. Interim Analysis (IA) planned when 60% of subjects had completed study or discontinued prematurely to assess efficacy (nominal 2-sided p-value less than or equal to [≤] 0.0076) or futility (nominal 2-sided p-value greater than or equal to [≥] 0.5099).	ANCOVA Mixed-effects repeated-measures	No other adjustment made for multiple comparisons since all comparisons, except for single primary comparison, are considered secondary.	0.7921	Due to planned interim analysis of primary endpoint, to control type I error at 2-sided alpha=0.05, a nominal 2-sided p-value ≤0.0476 needed at final analysis to reject the null hypothesis of no treatment effect.	Least squares mean	-0.36	Standard Error of the Mean	1.37		95	-3.07	2.34

Secondary

Change From Baseline to Week 6 in Clinical Global Impression - Severity Scale (CGI-Severity or CGI-S)

CGI-S is a single-item clinician rated scale used to assess global severity of bipolar illness based on an overall evaluation of symptoms of bipolar mania, associated behavioral symptoms, and condition of the subject. Scored from 1 (normal, not at all ill) to 7 (among the most severely ill subjects). Higher score = more affected. Change calculated as a difference between post-baseline observation and baseline CGI-S score values.

ITT

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

MADRS Remission: Number of Subjects With Total MADRS Score ≤ 12 at Week 6

Number of subjects with MADRS total score ≤ 12 (indicates remission). MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms).

ITT; Last observation carried forward (LOCF)

Posted

Number

participants

Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

MADRS Response: Number of Subjects With Total MADRS Score Reduction ≥ 50 Percent From Baseline at Week 6

Number of subjects with reduction of ≥50 percent (%) in MADRS total score (indicates response). MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts); rated on a 7-point Likert scale 0 (normal) to 6 (most abnormal); total score 0 to 44 (higher score indicates greater severity of symptoms). Reduction calculated as ([A-B]/B*100): A=value at observation; B=baseline value.

ITT; LOCF

Posted

Number

participants

Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

Clinical Global Impression - Improvement Scale (CGI-Improvement or CGI-I): Number of Subjects With Response (Much Improved or Very Much Improved) at Week 6

Number of subjects with improvement defined as CGI-I response of 1 (very much improved) or 2 (much improved). CGI-I is a single-item clinician rated scale used to assess global improvement in the subject's clinical state (bipolar mania) in response to study treatment and as compared to their status at pre-treatment baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse). Higher score = more affected.

ITT; LOCF

Posted

Number

participants

Baseline, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

Change From Baseline in MADRS Total Score (Post-baseline Excluding Week 6)

ITT; LOCF; (n)=number of subjects with analyzable data: baseline and post-baseline observation for ziprasidone, placebo, respectively.

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 1, Week 2, Week 3, Week 4, Week 5

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

Change From Baseline in CGI-Severity Score (Post-baseline Excluding Week 6)

CGI-S is a single-item clinician rated scale used to assess global severity of bipolar illness based on an overall evaluation of symptoms of bipolar mania, associated behavioral symptoms, and condition of the subject. Scores range from 1 (normal, not at all ill) to 7 (among the most severely ill subjects). Higher score = more affected. Change calculated as a difference between post-baseline observation and baseline CGI-S score values.

ITT; LOCF; (n)=number of subjects with analyzable data: baseline and post-baseline observation for ziprasidone, placebo, respectively.

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 1, Week 2, Week 3, Week 4, Week 5

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

CGI-Improvement Score

CGI-I is a single-item clinician rated scale used to assess global improvement in the subject's clinical state (bipolar mania) in response to study treatment and as compared to their status at pre-treatment baseline. Scores range from 1 (very much improved) to 4 (no change) to 7 (very much worse). Higher score = more affected. Week 6 is the primary timepoint.

ITT; LOCF; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

Posted

Mean

Standard Deviation

scores on scale

Week 1, Week 2, Week 3, Week 4, Week 5, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

Change From Baseline in Hamilton Anxiety Scale (HAM-A) Total Score

HAM-A is a clinician rated 14-item scale that rates the intensity of psychic anxiety (items 1 to 6 and item 14) and somatic anxiety (items 7 to 13) on a 5-point severity scale; scores range from 0 (not present) to 4 (very severe); lower score indicates less affected. Change calculated as a difference between post-baseline observation and baseline HAM-A score values. Week 6 is the primary timepoint.

ITT; LOCF; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 2, Week 4, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

Change From Baseline in Young Mania Rating Scale (YMRS) Total Score

YMRS is clinician rated 11-item scale (elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, speech [rate and amount], language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight) used to assess the severity of manic symptoms and effect of treatment on mania severity. Seven items ranked on scale from 0 to 4; 4 items ranked 0 to 8. Higher scores indicate greater severity. Change calculated as a difference between post-baseline observation and baseline YMRS score values. Week 6 is the primary timepoint.

ITT; LOCF; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

Change From Baseline in Global Assessment of Functioning (GAF) Scale at Week 6

GAF is a clinician rated scale to measure the severity of illness-related impairment in psychological, social, and occupational functioning using a 100-point scale (single score of 1 to 100) with 100 indicating a superior level of function. Change calculated as a difference between post-baseline observation and baseline GAF score values.

ITT; observed cases; Early Termination (ET) visits re-slotted to regular weekly visits according to duration since first dosing date; ET Visit only includes observations from visits that did not meet windowing criteria; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 1 Through 3)

SDS is a 5-item subject rated scale to measure the extent to which work and or school, social life and or leisure activities, and home life and or family responsibilities were impaired by psychiatric illness. Items 1 to 3 rated on 11-point scale ranging 0 (not at all) to 10 (extremely affected). Total score 0 to 30; higher score indicates greater impairment; items 4 and 5 report number of days in the last month (0 to 31) subject missed work or school or was unproductive and are rated separately. Change calculated as a difference between post-baseline observation and baseline SDS score values.

ITT; ET visits re-slotted to regular weekly visits according to duration since first dosing date; ET Visit only includes observations from visits that did not meet windowing criteria; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

Change From Baseline in Sheehan Disability Scale (SDS) at Week 6 (Items 4 and 5)

Posted

Mean

Standard Deviation

days

Baseline, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Other Pre-specified

Change From Baseline in Simpson Angus Scale (SAS) Score

SAS is a clinician rated 10-item scale to measure extrapyramidal side effects (Parkinsonism or Parkinsonian side effects induced with antipsychotics); rated on a 5-point scale with range 0 (absence of condition) to 4 (presence of condition in extreme form). Global score is sum of all scores divided by the total number of items. Change calculated as a difference between post-baseline observation and baseline SAS score values.

ITT; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 2, Week 4, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Other Pre-specified

Change From Baseline in Barnes Akathisia Rating Scale (BARS or BAS)

BARS is a clinician rated scale to evaluate akathisia associated with use of antipsychotic medications: objective motor restlessness, range 0 to 3; subjective complaints of restlessness and associated distress, range 0 to 3; global clinical assessment of akathisia, range 0 to 5. Higher scores indicate more affected. Change calculated as a difference between post-baseline observation and baseline BARS score values.

ITT; Summarized as Global BARS; individual scores not summarized; (n)=number of subjects with analyzable data at observation for ziprasidone and placebo, respectively.

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 2, Week 4, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Other Pre-specified

Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Scores

AIMS is a clinician rated 12-item scale to rate 7 body areas and global judgments on the severity of abnormal movements, incapacitation and subject's awareness of abnormal movements. Items 1 to 10 scored 0 (none) to 4 (severe); items 11 to 14 are No or Yes response to dental status and sleep movements and are assessed separately. AIMS total score is sum of first 7 items. Change calculated as a difference between post-baseline observation and baseline AIMS score values.

ITT; (n)=number of subjects with analyzable data at baseline and post-baseline observation for ziprasidone and placebo, respectively.

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 2, Week 4, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Secondary

Change From Baseline in Quality of Life, Enjoyment, and Satisfaction Scale (Q-LES-Q) Scores at Week 6

Q-LES-Q is a 16-item subject rated scale to measure satisfaction with areas of daily functioning (physical health, social relationships, medication, and overall life satisfaction); rated on a 5-point Likert scale: higher scores indicate greater enjoyment and satisfaction with general life activities. Scores for items 1 to 14 are summed for a total score and converted to 0 to 100 range. Items 15 and 16 measure satisfaction with medication and overall satisfaction and are analyzed separately. Change calculated as a difference between post-baseline observation and baseline Q-LES-Q score values.

Posted

Mean

Standard Deviation

scores on scale

Baseline, Week 6

ID	Title	Description
OG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).
OG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ziprasidone	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).			1	147	96	147
EG001	Placebo	Day 1: single dose of 40 milligrams (mg) by mouth (PO); Day 2: 40 mg po twice a day (BID); Day 3 through Week 6: flexible BID dosing titrated to a total daily dose of 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, or 160 mg as adjunctive therapy with a mood stabilizer (lithium, valproate, or lamotrigine).			6	147	57	147

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Palpitations	Cardiac disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk
Bipolar I disorder	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Intentional self-injury	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Mania	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected147 at risk EG0012 affected147 at risk
Suicidal ideation	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0000 affected147 at risk EG0011 affected147 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 affected147 at risk EG0010 affected147 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0007 affected147 at risk EG00111 affected147 at risk
Nausea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG00016 affected147 at risk EG0018 affected147 at risk
Fatigue	General disorders	MedDRA (12.0)	Systematic Assessment	EG00019 affected147 at risk EG0016 affected147 at risk
Akathisia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0008 affected147 at risk EG0012 affected147 at risk
Dizziness	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG00019 affected147 at risk EG0019 affected147 at risk
Headache	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG00017 affected147 at risk EG00114 affected147 at risk
Sedation	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG00021 affected147 at risk EG0017 affected147 at risk
Somnolence	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG00033 affected147 at risk EG0017 affected147 at risk
Tremor	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG00013 affected147 at risk EG00110 affected147 at risk
Anxiety	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0009 affected147 at risk EG0011 affected147 at risk
Insomnia	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG00017 affected147 at risk EG00110 affected147 at risk
Restlessness	Psychiatric disorders	MedDRA (12.0)	Systematic Assessment	EG0008 affected147 at risk EG0012 affected147 at risk

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	Week 6; MMRM analysis of covariance model with fixed categorical effects of treatment, country, type of mood stabilizer, visit, treatment-by-visit interaction, fixed continuous effect of baseline value and subject as random effect.	ANCOVA Mixed-effects repeated-measures		0.7223		Least squares mean	0.06	Standard Error of the Mean	0.16		95	-0.25	0.36					Superiority or Other (legacy)

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	Week 6; LOCF; Logistic regression model with treatment, country, and type of mood stabilizer.	Regression, Logistic		0.5029		Odds Ratio (OR)	0.846				95	0.52	1.38			Odds ratio measures the odds of achieving remission (MADRS total score ≤ 12) from ziprasidone treated subjects versus placebo; a value > 1 favors ziprasidone.		Superiority or Other (legacy)

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	Week 6; LOCF; Logistic regression model with treatment, country, and type of mood stabilizer.	Regression, Logistic		0.8266		Odds Ratio (OR)	0.949				95	0.59	1.52			Odds ratio measures the odds of achieving response (≥ 50 % reduction in MADRS total score) from ziprasidone treated subjects versus placebo; a value > 1 favors ziprasidone.		Superiority or Other (legacy)

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	Week 6; LOCF; Logistic regression model with treatment, country, and type of mood stabilizer.	Regression, Logistic		0.7924	Logistic regression model with treatment, country, and type of mood stabilizer.	Odds Ratio (OR)	0.939				95	0.59	1.50					Superiority or Other (legacy)

Title

Denominators

Categories

Week 1 (n=142, 141)

Title	Measurements
	OG000-8.1± 7.9 OG001-6.1± 7.3

Week 2 (n=121, 139)

Title	Measurements
	OG000-11.7± 8.9 OG001-9.0± 8.6

Week 3 (n=115, 130)

Title	Measurements
	OG000-13.0± 9.5 OG001-11.0± 9.2

Week 4 (n=106, 122)

Title	Measurements
	OG000-14.1± 9.6 OG001-11.8± 9.5

Week 5 (n=103, 112)

Title	Measurements
	OG000-14.9± 9.4 OG001-13.3± 10.1

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Week 1; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.0594	Least squares mean	-1.68	Standard Error of the Mean	0.89	95	-3.42	0.07	Superiority or Other (legacy)
OG000 OG001	Week 2; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.2230	Least squares mean	-1.25	Standard Error of the Mean	1.03	95	-3.27	0.77	Superiority or Other (legacy)
OG000 OG001	Week 3; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.6971	Least squares mean	-0.43	Standard Error of the Mean	1.09	95	-2.57	1.72	Superiority or Other (legacy)
OG000 OG001	Week 4; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.5485	Least squares mean	-0.68	Standard Error of the Mean	1.12	95	-2.89	1.54	Superiority or Other (legacy)
OG000 OG001	Week 5; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.8322	Least squares mean	-0.25	Standard Error of the Mean	1.19	95	-2.60	2.10	Superiority or Other (legacy)

Title

Denominators

Categories

Week 1 (n=142, 141)

Title	Measurements
	OG000-0.5± 0.8 OG001-0.4± 0.8

Week 2 (n=120, 139)

Title	Measurements
	OG000-0.9± 1.1 OG001-0.7± 0.9

Week 3 (n=115, 130)

Title	Measurements
	OG000-0.9± 1.0 OG001-0.9± 1.0

Week 4 (n=106, 122)

Title	Measurements
	OG000-1.1± 1.1 OG001-1.1± 1.1

Week 5 (n=103, 112)

Title	Measurements
	OG000-1.3± 1.2 OG001-1.3± 1.2

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Week 1; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.1771	Least squares mean	-0.12	Standard Error of the Mean	0.09	95	-0.29	0.05	Superiority or Other (legacy)
OG000 OG001	Week 2; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.1765	Least squares mean	-0.15	Standard Error of the Mean	0.11	95	-0.37	0.07	Superiority or Other (legacy)
OG000 OG001	Week 3; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.6765	Least squares mean	-0.05	Standard Error of the Mean	0.11	95	-0.27	0.18	Superiority or Other (legacy)
OG000 OG001	Week 4; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.9770	Least squares mean	0.00	Standard Error of the Mean	0.12	95	-0.24	0.25	Superiority or Other (legacy)
OG000 OG001	Week 5; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.7907	Least squares mean	-0.04	Standard Error of the Mean	0.13	95	-0.30	0.23	Superiority or Other (legacy)

Title

Denominators

Categories

Week 1 (n=142, 141)

Title	Measurements
	OG0003.2± 0.9 OG0013.4± 0.8

Week 2 (n=120, 138)

Title	Measurements
	OG0002.9± 1.1 OG0013.1± 1.0

Week 3 (n=115, 130)

Title	Measurements
	OG0002.7± 1.0 OG0012.9± 1.0

Week 4 (n=106, 122)

Title	Measurements
	OG0002.6± 1.2 OG0012.8± 1.2

Week 5 (n=103, 112)

Title	Measurements
	OG0002.5± 1.2 OG0012.6± 1.1

Week 6 (n=92, 108)

Title	Measurements
	OG0002.4± 1.2 OG0012.4± 1.1

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Week 1; LOCF; Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.	ANOVA	0.0392		Least squares mean	-0.22	Standard Error of the Mean	0.11	95	-0.43	-0.01	Superiority or Other (legacy)
OG000 OG001	Week 2; LOCF; Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.	ANOVA	0.2803		Least squares mean	-0.14	Standard Error of the Mean	0.13	95	-0.38	0.11	Superiority or Other (legacy)
OG000 OG001	Week 3; LOCF; Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.	ANOVA	0.9835		Least squares mean	-0.00	Standard Error of the Mean	0.13	95	-0.26	0.26	Superiority or Other (legacy)
OG000 OG001	Week 4; LOCF; Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.	ANOVA	0.7062		Least squares mean	-0.06	Standard Error of the Mean	0.15	95	-0.34	0.23	Superiority or Other (legacy)
OG000 OG001	Week 5; LOCF; Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.	ANOVA	0.9518		Least squares mean	-0.01	Standard Error of the Mean	0.15	95	-0.31	0.29	Superiority or Other (legacy)
OG000 OG001	Week 6; LOCF	ANOVA	0.4757	Analysis of variance model with treatment, country, type of mood stabilizer as fixed effects.	Least squares mean	0.11	Standard Error of the Mean	0.16	95	-0.20	0.42	Superiority or Other (legacy)

Title

Denominators

Categories

Week 2 (n=136, 141)

Title	Measurements
	OG000-5.6± 6.8 OG001-5.9± 6.7

Week 4 (n=111, 127)

Title	Measurements
	OG000-7.1± 7.2 OG001-7.4± 7.6

Week 6 (n=100, 111)

Title	Measurements
	OG000-8.5± 7.9 OG001-8.6± 7.5

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Week 2; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.6362	Least squares mean	0.35	Standard Error of the Mean	0.75	95	-1.12	1.82	Superiority or Other (legacy)
OG000 OG001	Week 4; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.4565	Least squares mean	0.59	Standard Error of the Mean	0.80	95	-0.98	2.17	Superiority or Other (legacy)
OG000 OG001	Week 6; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.4770	Least squares mean	0.61	Standard Error of the Mean	0.86	95	-1.08	2.30	Superiority or Other (legacy)

Title

Denominators

Categories

Week 1 (n=142, 141)

Title	Measurements
	OG0000.7± 4.4 OG001-0.2± 3.5

Week 2 (n=121, 139)

Title	Measurements
	OG0000.5± 4.5 OG001-0.2± 4.3

Week 3 (n=115, 130)

Title	Measurements
	OG000-0.0± 4.5 OG001-0.2± 4.9

Week 4 (n=106, 122)

Title	Measurements
	OG000-0.9± 4.1 OG001-1.1± 4.2

Week 5 (n=103, 112)

Title	Measurements
	OG000-0.9± 3.9 OG001-1.3± 4.1

Week 6 (n=92, 108)

Title	Measurements
	OG000-1.0± 4.8 OG001-0.9± 4.6

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Week 1; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.1277	Least squares mean	0.70	Standard Error of the Mean	0.46	95	-0.20	1.60	Superiority or Other (legacy)
OG000 OG001	Week 2; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.2345	Least squares mean	0.64	Standard Error of the Mean	0.53	95	-0.41	1.68	Superiority or Other (legacy)
OG000 OG001	Week 3; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.8337	Least squares mean	0.13	Standard Error of the Mean	0.60	95	-1.05	1.30	Superiority or Other (legacy)
OG000 OG001	Week 4; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.4646	Least squares mean	0.43	Standard Error of the Mean	0.59	95	-0.73	1.59	Superiority or Other (legacy)
OG000 OG001	Week 5; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.3993	Least squares mean	0.50	Standard Error of the Mean	0.59	95	-0.67	1.67	Superiority or Other (legacy)
OG000 OG001	Week 6; LOCF; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.7647	Least squares mean	0.19	Standard Error of the Mean	0.65	95	-1.08	1.46	Superiority or Other (legacy)

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	Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA		0.0108		Least squares mean	4.24	Standard Error of the Mean	1.65		95	0.99	7.50					Superiority or Other (legacy)

Title

Denominators

Categories

Total SDS: Week 6 (n=58, 63)

Title	Measurements
	OG000-8.5± 9.2 OG001-3.7± 8.2

Total SDS: ET (n=19, 14)

Title	Measurements
	OG0000.2± 6.8 OG001-1.4± 6.7

Work/School: Week 6 (n=58, 64)

Title	Measurements
	OG000-2.1± 3.5 OG001-1.6± 2.9

Work/School: ET (n=19, 14)

Title	Measurements
	OG0000.4± 3.0 OG001-0.1± 2.7

Social life: Week 6 (n=94, 102)

Title	Measurements
	OG000-2.5± 3.3 OG001-1.7± 3.2

Social life: ET (n=31, 23)

Title	Measurements
	OG000-0.5± 2.9 OG0010.1± 3.1

Family/Home: Week 6 (n=94, 102)

Title	Measurements
	OG000-2.6± 3.2 OG001-1.7± 3.3

Family/Home: ET (n=31, 23)

Title	Measurements
	OG0000.2± 2.3 OG001-0.6± 3.2

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	Total SDS: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA		0.0010		Least squares mean	-4.56	Standard Error of the Mean	1.35		95	-7.24	-1.87					Superiority or Other (legacy)

Title

Denominators

Categories

Days lost: Week 6 (n=85, 93)

Title	Measurements
	OG000-1.2± 2.5 OG001-0.7± 2.3

Days lost: ET (n=29, 21)

Title	Measurements
	OG0000.5± 2.7 OG0010.0± 2.2

Days unproductive: Week 6 (n=87, 89)

Title	Measurements
	OG000-1.6± 2.8 OG001-1.3± 2.9

Days unproductive: ET (n=29, 21)

Title	Measurements
	OG000-0.2± 2.5 OG001-0.1± 3.7

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	Days Lost: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA		0.1230		Least squares mean	-0.44	Standard Error of the Mean	0.28	2-Sided	95	-1.00	0.12					Superiority or Other (legacy)
OG000 OG001	Days Unproductive: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA		0.6232		Least squares mean	-0.17	Standard Error of the Mean	0.34	2-Sided	95	-0.84	0.50					Superiority or Other (legacy)

Title

Denominators

Categories

Week 2 (n=136, 141)

Title	Measurements
	OG0000.1± 0.8 OG001-0.1± 0.7

Week 4 (n=111, 126)

Title	Measurements
	OG0000.0± 0.8 OG0010.0± 0.6

Week 6 (n=100, 110)

Title	Measurements
	OG0000.0± 0.7 OG001-0.1± 0.7

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Week 2; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.0096	Least squares mean	0.17	Standard Error of the Mean	0.07	95	0.04	0.31	Superiority or Other (legacy)
OG000 OG001	Week 4; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.8134	Least squares mean	0.02	Standard Error of the Mean	0.07	95	-0.13	0.16	Superiority or Other (legacy)
OG000 OG001	Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.0226	Least squares mean	0.16	Standard Error of the Mean	0.07	95	0.02	0.29	Superiority or Other (legacy)

Title

Denominators

Categories

Week 2 (n=135, 139)

Title	Measurements
	OG0000.1± 0.5 OG001-0.0± 0.4

Week 4 (n=111, 125)

Title	Measurements
	OG0000.0± 0.5 OG0010.0± 0.5

Week 6 (n=100, 110)

Title	Measurements
	OG0000.0± 0.6 OG001-0.0± 0.5

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Week 2; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.0193	Least squares mean	0.12	Standard Error of the Mean	0.05	95	0.02	0.23	Superiority or Other (legacy)
OG000 OG001	Week 4; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.4745	Least squares mean	0.04	Standard Error of the Mean	0.06	0.16	-0.07	0.16	Superiority or Other (legacy)
OG000 OG001	Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.2613	Least squares mean	0.07	Standard Error of the Mean	0.06	95	-0.05	0.19	Superiority or Other (legacy)

Title

Denominators

Categories

Total score: Week 2 (n=136, 142)

Title	Measurements
	OG0000.1± 0.7 OG001-0.1± 0.4

Total score: Week 4 (n=111, 127)

Title	Measurements
	OG000-0.0± 0.5 OG001-0.0± 0.5

Total score: Week 6 (n=100, 111)

Title	Measurements
	OG000-0.0± 0.6 OG001-0.0± 0.4

Global severity score: Week 2 (n=136, 142)

Title	Measurements
	OG0000.0± 0.4 OG001-0.0± 0.2

Global severity score: Week 4 (n=111, 127)

Title	Measurements
	OG0000.0± 0.3 OG0010.0± 0.2

Global severity score: Week 6 (n=100, 111)

Title	Measurements
	OG0000.0± 0.3 OG0010.0± 0.1

Incapacitation score: Week 2 (n=136, 142)

Title	Measurements
	OG0000.0± 0.2 OG001-0.0± 0.1

Incapacitation score: Week 4 (n=111, 127)

Title	Measurements
	OG0000.0± 0.1 OG001-0.0± 0.2

Incapacitation score: Week 6 (n=100, 111)

Title	Measurements
	OG0000.0± 0.1 OG0010.0± 0.2

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Total score: Week 2; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.0271	Least squares mean	0.11	Standard Error of the Mean	0.05	95	0.01	0.21	Superiority or Other (legacy)
OG000 OG001	Total score: Week 4; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.7462	Least squares mean	-0.01	Standard Error of the Mean	0.03	95	-0.07	0.05	Superiority or Other (legacy)
OG000 OG001	Total score: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.9574	Least squares mean	0.00	Standard Error of the Mean	0.04	95	-0.08	0.08	Superiority or Other (legacy)
OG000 OG001	Global severity score: Week 2; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.0844	Least squares mean	0.05	Standard Error of the Mean	0.03	95	-0.01	0.10	Superiority or Other (legacy)
OG000 OG001	Global severity score: Week 4; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.5779	Least squares mean	0.01	Standard Error of the Mean	0.02	95	-0.04	0.06	Superiority or Other (legacy)
OG000 OG001	Global severity score: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.7455	Least squares mean	0.01	Standard Error of the Mean	0.03	95	-0.05	0.06	Superiority or Other (legacy)
OG000 OG001	Incapacitation score: Week 2; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.3278	Least squares mean	0.02	Standard Error of the Mean	0.02	95	-0.02	0.05	Superiority or Other (legacy)
OG000 OG001	Incapacitation score: Week 4; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.9097	Least squares mean	0.00	Standard Error of the Mean	0.01	95	-0.03	0.03	Superiority or Other (legacy)
OG000 OG001	Incapacitation score: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.9864	Least squares mean	0.00	Standard Error of the Mean	0.02	95	-0.04	0.04	Superiority or Other (legacy)

Title

Denominators

Categories

Total Q-LES-Q: Week 6 (n=82, 94)

Title	Measurements
	OG00015.2± 19.0 OG00111.6± 17.3

Total Q-LES-Q: ET (n=27, 17)

Title	Measurements
	OG000-0.1± 19.7 OG0011.6± 14.5

Medications: Week 6 (n=91, 93)

Title	Measurements
	OG0000.4± 1.2 OG0010.3± 1.1

Medications: ET (n=27, 20)

Title	Measurements
	OG000-0.3± 1.2 OG001-0.4± 0.8

Overall life satisfaction: Week 6 (n=94, 103)

Title	Measurements
	OG0000.8± 1.1 OG0010.5± 1.1

Overall life satisfaction: ET (n=31, 23)

Title	Measurements
	OG0000.1± 1.3 OG0010.0± 0.9

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Total Q-LES-Q: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.5519	Least squares mean	1.52	Standard Error of the Mean	2.54	95	-3.50	6.53	Superiority or Other (legacy)
OG000 OG001	Medications: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.5238	Least squares mean	-0.09	Standard Error of the Mean	0.13	95	-0.35	0.18	Superiority or Other (legacy)
OG000 OG001	Overall life satisfaction: Week 6; Observed cases; Analysis of covariance model with treatment, country, type of mood stabilizer as fixed effects and baseline score as covariate.	ANCOVA	0.5360	Least squares mean	0.09	Standard Error of the Mean	0.14	95	-0.19	0.36	Superiority or Other (legacy)

ID	Term
D000068105	Bipolar and Related Disorders
D019964	Mood Disorders
D001523	Mental Disorders