Safety and Efficacy of Cariprazine as an Adjunctive to An... | NCT01469377

Status Module

Name	Class
Gedeon Richter Ltd.	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.	Drug: Placebo
Cariprazine 1-2 mg	Experimental	Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.	Drug: Cariprazine
Cariprazine 2-4.5 mg	Experimental	Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Placebo was supplied in capsules	Placebo
Cariprazine

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8	The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.	Baseline to Week 8

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Sheehan Disability Scale (SDS) Total Score at Week 8	The SDS measures an individual's perception of the extent to which his or her emotional symptoms are disrupting his or her functioning in 3 domains, work/school, social life/leisure activities, and family life/home responsibilities. 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.

Eligibility Module

Name	Affiliation	Role
Willie Earley, MD	Allergan	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Forest Investigative Site 077		Garden Grove	California	92845	United States
Forest Investigative Site 019

PubMed Identifier	Type	Citation	Retractions
27046309	Derived	Durgam S, Earley W, Guo H, Li D, Nemeth G, Laszlovszky I, Fava M, Montgomery SA. Efficacy and safety of adjunctive cariprazine in inadequate responders to antidepressants: a randomized, double-blind, placebo-controlled study in adult patients with major depressive disorder. J Clin Psychiatry. 2016 Mar;77(3):371-8. doi: 10.4088/JCP.15m10070.

ID	Title	Description
FG000	Placebo	Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
BG001	Cariprazine 1-2 mg	Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
BG002	Cariprazine 2-4.5 mg	Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
BG003	Total	Total of all reporting groups

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 in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8

The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.

Intent-to-treat population consisted of all patients in the Safety Population who had at least 1 post-baseline assessment of the MADRS total score.

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline to Week 8

ID	Title	Description
OG000	Placebo	Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
OG001	Cariprazine 1-2 mg	Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
OG002	Cariprazine 2-4.5 mg	Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.

Units	Counts
Participants	OG000264 OG001273 OG002271

Title

Denominators

Categories

Title	Measurements
	OG000-12.5± 0.5 OG001-13.4± 0.5 OG002-14.6± 0.6

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		Mixed-effect model for repeated measures	p-values were adjusted for multiple comparisons using the matched parallel gate-keeping procedure.	0.2404	p-values were from an mixed-effects model for repeated measures with treatment group, pooled study center, visit, and treatment-group-by-visit interaction as fixed effects and the baseline value and baseline value-by-visit interaction as covariates.	Least squares mean difference	-0.9			2-Sided	95	-2.4	0.6					Superiority

Secondary

Change From Baseline in the Sheehan Disability Scale (SDS) Total Score at Week 8

The SDS measures an individual's perception of the extent to which his or her emotional symptoms are disrupting his or her functioning in 3 domains, work/school, social life/leisure activities, and family life/home responsibilities. 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.

Intent-to-treat population consisted of all patients in the Safety Population who had at least 1 post-baseline assessment of the MADRS total score. Only participants with scores for all 3 domains were included in the analysis.

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline to Week 8

ID	Title	Description
OG000	Placebo	Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.
OG001	Cariprazine 1-2 mg

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.	266	1	266	102	266
EG001	Cariprazine 1-2 mg	Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.	273	0	273	121	273
EG002	Cariprazine 2-4.5 mg	Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.	273	3	273	179	273

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0005 affected266 at risk EG0016 affected273 at risk EG00214 affected273 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG00014 affected266 at risk EG0018 affected273 at risk EG0028 affected273 at risk
Dry mouth	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0007 affected266 at risk EG00114 affected273 at risk EG00210 affected273 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 16.1	Systematic Assessment	EG00013 affected266 at risk EG00119 affected273 at risk EG00235 affected273 at risk
Fatigue	General disorders	MedDRA Version 16.1	Systematic Assessment	EG00011 affected266 at risk EG00118 affected273 at risk EG00227 affected273 at risk
Increased appetite	Metabolism and nutrition disorders	MedDRA Version 16.1	Systematic Assessment	EG0004 affected266 at risk EG0015 affected273 at risk EG00214 affected273 at risk
Akathisia	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0006 affected266 at risk EG00118 affected273 at risk EG00261 affected273 at risk
Dizziness	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0007 affected266 at risk EG00110 affected273 at risk EG00214 affected273 at risk
Headache	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG00036 affected266 at risk EG00124 affected273 at risk EG00224 affected273 at risk
Somnolence	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG00014 affected266 at risk EG00124 affected273 at risk EG00227 affected273 at risk
Tremor	Nervous system disorders	MedDRA Version 16.1	Systematic Assessment	EG0004 affected266 at risk EG00113 affected273 at risk EG00221 affected273 at risk
Insomnia	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG00017 affected266 at risk EG00127 affected273 at risk EG00238 affected273 at risk
Restlessness	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0007 affected266 at risk EG00122 affected273 at risk EG00223 affected273 at risk

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

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Non-cardiac chest pain	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected266 at risk EG0010 affected273 at risk EG0021 affected273 at risk
Agitation	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected266 at risk EG0010 affected273 at risk EG0021 affected273 at risk
Panic attack	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected266 at risk EG0010 affected273 at risk EG0021 affected273 at risk
Depression	Psychiatric disorders	MedDRA Version 16.1	Systematic Assessment	EG0001 affected266 at risk EG0010 affected273 at risk EG0020 affected273 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected266 at risk EG0010 affected273 at risk EG0021 affected273 at risk
Myocardial ischemia	Cardiac disorders	MedDRA Version 16.1	Systematic Assessment	EG0000 affected266 at risk EG0010 affected273 at risk EG0021 affected273 at risk