Study to Evaluate the Efficacy, Safety and Tolerability o... | NCT01111539

NCT01111539

ID	Type	Description	Link
2010-018796-21	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase B: Single-blind Prospective Treatment Phase	Experimental	Participants received initial dose of escitalopram 10 milligram (mg) blinded capsule (over-encapsulated tablet), orally, once daily, increased to 20 mg/day at the end of Week 1 based upon tolerability profile, for up to maximum of Week 8. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.	Drug: Escitalopram Drug: Blinded capsule
Phase B+: Single-blind Phase B Responders	Experimental	Participants with response (≥50% reduction in depressive symptom severity in Hamilton Depression Rating Scale {HAM-D17} Total Score; or a HAM-D17 Total Score of <14 at Week 8 or a Clinical Global Impression of Improvement {CGI-I} Score of <3 at the Week 6 or 8) at the end of the Phase B (Week 8) continued treatment with the single-blind escitalopram monotherapy at the dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B, for up to maximum of Week 14, in Phase B+.	Drug: Escitalopram Drug: Blinded capsule
Phase C: Aripiprazole/Escitalopram Combination	Experimental	Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Escitalopram	Drug	Escitalopram capsule administered orally, once daily without regard to meals.	Phase B+: Single-blind Phase B Responders Phase B: Single-blind Prospective Treatment Phase

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase C: Mean Change From End of Phase B (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to End of Phase C (Week 14)	The MADRS assessed severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms). Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). A negative change from Week 8 indicates improvement.	Week 8 to Week 14

Secondary Outcomes

Measure	Description	Time Frame
Phase C: Mean Clinical Global Impression - Improvement (CGI-I) Scale Score at the End of Phase C (Week 14)	CGI-I is a 7-point clinician-rated scale ranging from 1 to 7, rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. A higher score indicates greater impairment.	Week 14

Eligibility Module

Facility	Status	City	State	ZIP	Country	Contacts
		Cerritos	California	90703	United States

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Phase B: Single-blind Prospective Treatment Phase	Participants received initial dose of escitalopram 10 milligram (mg) blinded capsule (over-encapsulated tablet), orally, once daily, increased to 20 mg/day at the end of Week 1 based upon tolerability profile, for up to maximum of Week 8. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Phase C: Mean Change From End of Phase B (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to End of Phase C (Week 14)

The MADRS assessed severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms). Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). A negative change from Week 8 indicates improvement.

ITT Sample included all participants in the Randomized Sample who received at least one dose of double-blind study medication and had at least one post-randomization efficacy evaluation.

Posted

Least Squares Mean

Standard Error

score on a scale

Week 8 to Week 14

ID	Title	Description
OG000	Phase C: Aripiprazole/Escitalopram Combination	Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C.
OG001	Phase C: Escitalopram Monotherapy	Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received escitalopram dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.
OG002	Phase C: Aripiprazole Monotherapy	Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily for Week 9. Participants were up titrated to the aripiprazole target dose of 12 mg/day at Week 10 (if the initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on the initial 6 mg/day dose), and thereafter received the same dose for up to maximum of Week 14. No dose increases were allowed for aripiprazole after the end of Week 12, however, doses might be decreased at any visit based upon tolerability.

Units	Counts
Participants	OG00028 OG00127 OG00228

Title

Denominators

Categories

Title	Measurements
	OG000-8.0± 1.5 OG001-7.0± 1.5 OG002-4.3± 1.5

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	The statistical analyses was performed by fitting an analysis of covariance (ANCOVA) model to the change from baseline data (Week 8 Visit) for the MADRS Total Score at the Week 14 visit (LOCF). The model included baseline MADRS Total Score as a covariate and treatment as the main effect.	ANCOVA		=0.644		Treatment Difference	-1.0			2-Sided	95	-5.2	3.3					Superiority

Secondary

Phase C: Mean Clinical Global Impression - Improvement (CGI-I) Scale Score at the End of Phase C (Week 14)

CGI-I is a 7-point clinician-rated scale ranging from 1 to 7, rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. A higher score indicates greater impairment.

ITT Sample included all participants in the Randomized Sample who received at least one dose of double-blind study medication and had at least one post-randomization efficacy evaluation.

Posted

Mean

Standard Error

score on a scale

Week 14

ID	Title	Description
OG000	Phase C: Aripiprazole/Escitalopram Combination	Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C.

Secondary

Phase C: Mean Change From End of Phase B (Week 8) in the Sheehan Disability Scale (SDS) Mean Score to End of Phase C (Week 14)

SDS is a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. The participant is asked to rate the degree to which their functioning is impaired on an 11-point scale, ranging from 0 (not at all) to 10 (extremely). The scores for the 3 domains are summed into a total score that ranges from 0 (unimpaired) to 30 (highly impaired). A higher score indicates greater impairment. A negative change from Week 8 indicates improvement.

ITT Sample included all participants in the Randomized Sample who received at least one dose of double-blind study medication and had at least one post-randomization efficacy evaluation. Overall number of participants analyzed are the participants with evaluable data for analyses.

Posted

Least Squares Mean

Standard Error

score on a scale

Week 8 to Week 14

ID	Title	Description
OG000	Phase C: Aripiprazole/Escitalopram Combination	Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase B: Single-blind Prospective Treatment Phase	Participants received initial dose of escitalopram 10 milligram (mg) blinded capsule (over-encapsulated tablet), orally, once daily, increased to 20 mg/day at the end of Week 1 based upon tolerability profile, for up to maximum of Week 8. No dose reductions were allowed after Week 4 and no dose increments were allowed after Week 3. Participants with incomplete response at the end of the Phase B (Week 8) entered Phase C and the rest of the participants continued to Phase B+.	211	2	211	82	211
EG001	Phase B+: Single-blind Phase B Responders	Participants with response (≥50% reduction in depressive symptom severity in Hamilton Depression Rating Scale {HAM-D17} Total Score; or a HAM-D17 Total Score of <14 at Week 8 or a Clinical Global Impression of Improvement {CGI-I} Score of <3 at the Week 6 or 8) at the end of the Phase B (Week 8) continued treatment with the single-blind escitalopram monotherapy at the dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B, for up to maximum of Week 14, in Phase B+.	45	0	45	3	45
EG002	Phase C: Aripiprazole/Escitalopram Combination	Participants with incomplete response (less than 50% reduction in depressive symptom severity between Baseline and Week 8 measured by the HAM-D17 Total Score and HAM-D17 Total Score of ≥14 at Week 8 and CGI-I Score of ≥3 at Week 6 and 8) at Week 8 received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily at Week 9. Participants were up titrated to aripiprazole target dose of 12 mg/day at Week 10 (if initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on initial 6 mg/day dose), and thereafter received same dose up to maximum of Week 14. No dose increases were allowed for aripiprazole after end of Week 12, however, doses might be decreased at any visit based upon tolerability. In combination with aripiprazole, participants received escitalopram (10 or 20 mg/day blinded capsules) taken during final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments allowed for escitalopram during Phase C.	28	0	28	18	28
EG003	Phase C: Escitalopram Monotherapy	Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received escitalopram dose (10 or 20 mg/day blinded capsules) taken during the final week of Phase B for up to maximum Week 14, in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.	27	1	27	11	27
EG004	Phase C: Aripiprazole Monotherapy	Participants with incomplete response (less than a 50% reduction in depressive symptom severity between the Baseline and Week 8 as measured by the HAM-D17 Total Score and a HAM-D17 Total Score of ≥14 at Week 8 and a CGI-I Score of ≥3 at Week 6 and 8) at Week 8, received initial dose of aripiprazole 6 mg blinded capsule, orally, once daily for Week 9. Participants were up titrated to the aripiprazole target dose of 12 mg/day at Week 10 (if the initial 6 mg/day dose was tolerated) or down titrated to 3 mg/day (if significant tolerability issues arise on the initial 6 mg/day dose), and thereafter received the same dose for up to maximum of Week 14. No dose increases were allowed for aripiprazole after the end of Week 12, however, doses might be decreased at any visit based upon tolerability.	28	1	28	17	28

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cholecystitis acute	Hepatobiliary disorders	MedDra 13.1	Systematic Assessment	EG0000 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG0031 affected27 at risk EG0040 affected28 at risk
Syncope	Nervous system disorders	MedDra 13.1	Systematic Assessment	EG0000 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDra 13.1	Systematic Assessment	EG0000 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDra 13.1	Systematic Assessment	EG0001 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDra 13.1	Systematic Assessment	EG0001 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDra 13.1	Systematic Assessment	EG0001 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Photophobia	Eye disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG0030 affected27 at risk EG0042 affected28 at risk
Vision blurred	Eye disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00012 affected211 at risk EG0011 affected45 at risk EG0020 affected28 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0008 affected211 at risk EG0011 affected45 at risk EG0021 affected28 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00021 affected211 at risk EG0010 affected45 at risk EG0021 affected28 at risk EG003
Feeling jittery	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected211 at risk EG0010 affected45 at risk EG0021 affected28 at risk EG003
Irritability	General disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected211 at risk EG0010 affected45 at risk EG0022 affected28 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG003
Increased appetite	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG003
Akathisia	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected211 at risk EG0010 affected45 at risk EG0022 affected28 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG003
Dizziness	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0006 affected211 at risk EG0010 affected45 at risk EG0021 affected28 at risk EG003
Dyskinesia	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG003
Headache	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG00036 affected211 at risk EG0011 affected45 at risk EG0022 affected28 at risk EG003
Sedation	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected211 at risk EG0010 affected45 at risk EG0022 affected28 at risk EG003
Somnolence	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG00012 affected211 at risk EG0010 affected45 at risk EG0023 affected28 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected211 at risk EG0010 affected45 at risk EG0023 affected28 at risk EG003
Restlessness	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected211 at risk EG0010 affected45 at risk EG0024 affected28 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected211 at risk EG0010 affected45 at risk EG0020 affected28 at risk EG003

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders
D001526	Behavioral Symptoms
D001519	Behavior

ID	Term
D011437	Propylamines
D000588	Amines
D009930	Organic Chemicals
D009570	Nitriles
D001572	Benzofurans
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D015363	Quinolones
D011804	Quinolines