Study to Evaluate the Efficacy, Safety and Tolerability o... | NCT01111565

ID	Type	Description	Link
2010-018859-97	EudraCT Number

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase B: Single-blind Prospective Treatment Phase	Experimental	Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the Week 1 (end of Week 1) based upon tolerability profile, for 8 weeks. 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
Phase B+: Single-blind Phase B Responders	Experimental	Participants with response (≥50% reduction in depressive symptom severity in 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) taken during the final week of Phase B, for an additional 6 weeks (Up to Week 14), in Phase B+.	Drug: Escitalopram
Phase C: Aripiprazole/Escitalopram Combination	Experimental	Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.	Drug: Escitalopram Drug: Aripiprazole
Phase C: Escitalopram Monotherapy

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 (or decrease) from baseline indicates a reduction (or improvement) in symptoms. Last observation carried forward (LOCF) method was used for analyses.	Week 8 to Week 14

Secondary Outcomes

Measure	Description	Time Frame
Phase C: Clinical Global Impression - Improvement Scale (CGI-I) Score at the End of Phase C	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. LOCF method was used for analyses.	Week 14

Eligibility Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Phase B: Single-blind Prospective Treatment Phase	Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the Week 1 (end of Week 1) based upon tolerability profile, for 8 weeks. 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 (or decrease) from baseline indicates a reduction (or improvement) in symptoms. Last observation carried forward (LOCF) method was used for analyses.

Intent-to-treat (ITT) Sample included all participants in the Randomized Sample who received at least one dose of double blind trial medication and had at least one post-randomization efficacy evaluation in Phase C.

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 at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
OG001	Phase C: Escitalopram Monotherapy	Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B for 6 weeks (Up to 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 at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily for 6 weeks (Up to Week 14), in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any visit, based upon tolerability.

Units	Counts
Participants	OG00016 OG00114 OG00215

Title

Denominators

Categories

Title	Measurements
	OG000-9.0± 2.1 OG001-3.6± 2.2 OG002-3.8± 2.1

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		ANCOVA		=0.079		Treatment Difference	-5.4			2-Sided	95	-11.5	0.7					Superiority
OG000 OG002		ANCOVA		=0.085

Secondary

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

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. LOCF method was used for analyses.

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

Posted

Mean

Standard Error

score on a scale

Week 14

ID	Title	Description
OG000	Phase C: Aripiprazole/Escitalopram Combination	Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.
OG001	Phase C: Escitalopram Monotherapy	Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram monotherapy 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). Scores of 0 to 3 indicate mild functional impairment, 4 to 6 indicate moderate functional impairment, and 7 to 9 indicate marked functional impairment. 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 score indicates improvement. LOCF method was used for analyses.

ITT Sample included all participants in the Randomized Sample who received at least one dose of double blind trial medication and had at least one post-randomization efficacy evaluation in Phase C. Overall number of participants analyzed are participants with data available 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 at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase B: Single-blind Prospective Treatment Phase	Escitalopram 10 mg capsule, orally, once daily increased to 20 mg/day at the Week 1 (end of Week 1) based upon tolerability profile, for 8 weeks. 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+.	137	137	65	137
EG001	Phase B+: Single-blind Phase B Responders	Participants with response (≥50% reduction in depressive symptom severity in 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) taken during the final week of Phase B, for an additional 6 weeks (Up to Week 14), in Phase B+.	26	26	4	26
EG002	Phase C: Aripiprazole/Escitalopram Combination	Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily in combination with the escitalopram 10 or 20 mg orally for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram during Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated.	16	16	12	16
EG003	Phase C: Escitalopram Monotherapy	Participants with incomplete response at Week 8 who were randomized to this arm group received escitalopram monotherapy 10 or 20 mg capsule, orally, once daily, whichever dose was taken during the final week of Phase B for 6 weeks (Up to Week 14), in Phase C. No dose adjustments were allowed for escitalopram monotherapy during Phase C.	14	14	11	14
EG004	Phase C: Aripiprazole Monotherapy	Participants with incomplete response at Week 8 who were randomized to this arm group received aripiprazole 3, 6, or 12 mg capsule, orally, once daily for 6 weeks (Up to Week 14), in Phase C. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 9 if the initial 6 mg/day dose was tolerated. No dose increments were allowed after Week 12; however, doses may have been decreased at any visit, based upon tolerability.	15	15	13	15

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dry mouth	Gastrointestinal disorders	MedDra 13.1	Systematic Assessment	EG0007 affected137 at risk EG0011 affected26 at risk EG0021 affected16 at risk EG0031 affected14 at risk EG0043 affected15 at risk
Nausea	Gastrointestinal disorders	MedDra 13.1	Systematic Assessment	EG00018 affected137 at risk EG0012 affected26 at risk EG0022 affected16 at risk EG003
Asthenia	General disorders	MedDra 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0022 affected16 at risk EG003
Fatigue	General disorders	MedDra 13.1	Systematic Assessment	EG0007 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDra 13.1	Systematic Assessment	EG0003 affected137 at risk EG0010 affected26 at risk EG0023 affected16 at risk EG003
Akathisia	Nervous system disorders	MedDra 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0022 affected16 at risk EG003
Dizziness	Nervous system disorders	MedDra 13.1	Systematic Assessment	EG0009 affected137 at risk EG0010 affected26 at risk EG0022 affected16 at risk EG003
Headache	Nervous system disorders	MedDra 13.1	Systematic Assessment	EG00015 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Lethargy	Nervous system disorders	MedDra 13.1	Systematic Assessment	EG0002 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Insomnia	Psychiatric disorders	MedDra 13.1	Systematic Assessment	EG0002 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Restlessness	Psychiatric disorders	MedDra 13.1	Systematic Assessment	EG0002 affected137 at risk EG0010 affected26 at risk EG0022 affected16 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Dry eye	Eye disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Vision blurred	Eye disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Salivary hypersecretion	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Irritability	General disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Bronchitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Sinusitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Viral infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Blood creatinine increased	Investigations	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Weight increased	Investigations	MedDRA 13.1	Systematic Assessment	EG0002 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Muscle rigidity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Trismus	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Ataxia	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Drooling	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Sedation	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Somnolence	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0008 affected137 at risk EG0011 affected26 at risk EG0021 affected16 at risk EG003
Tremor	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected137 at risk EG0010 affected26 at risk EG0022 affected16 at risk EG003
Visual field defect	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Initial insomnia	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Middle insomnia	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Allergic sinusitis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Yawning	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected137 at risk EG0010 affected26 at risk EG0021 affected16 at risk EG003
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003
Hot flush	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected137 at risk EG0010 affected26 at risk EG0020 affected16 at risk EG003

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

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