Safety and Efficacy of Cariprazine As Adjunctive Therapy... | NCT00854100

Status Module

Name	Class
Gedeon Richter Ltd.	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo	Drug: Antidepressant + placebo
Cariprazine 0.1 - 0.3 mg	Experimental	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR)+ cariprazine low dose	Drug: Antidepressant + cariprazine (0.1-0.3 mg/day)
Cariprazine 1.0 - 2.0 mg	Experimental	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine high dose	Drug: Antidepressant + cariprazine (1-2 mg/d)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Antidepressant + placebo	Drug	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo Oral, once daily for 8 weeks following an 8 week Prospective Treatment (Baseline) Period.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS)	The patient is rated on a scale from 0-6 on 10 items. Apparent sadness, reported sadness, lassitude, pessimistic thoughts, inner tension, suicidal thoughts, reduced sleep and appetite, concentration difficulties, inability to feel. The overall MADRS score ranges from 0-60, with 0 meaning no symptoms and score of 60 meaning maximum severity. The primary efficacy parameter was the change in MADRS score totals from the scores taken at Baseline (Week 8) and during at least one more time point up to and including Week 16.	Baseline (Week 8) to Week 16

Secondary Outcomes

Measure	Description	Time Frame
Clinical Global Impression - Improvement (CGI-I)	The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale that, in this study, will be used to rate total improvement or worsening of mental illness starting at Visit 2 (Week 2) and taken at every visit through Visit 11 (Week 16). The patient will be rated on a scale from 1 to 7, 1 indicating that the patient is very much improved and 7 indicating that the patient is very much worse. The secondary efficacy parameter was the CGI-I total score at Week 16.

Eligibility Module

Name	Affiliation	Role
Robert Hayes, PhD	Forest Laboratories	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Forest Investigative Site 040		Phoenix	Arizona	85050	United States
Forest Investigative Site 038

PubMed Identifier	Type	Citation	Retractions
30045066	Derived	Fava M, Durgam S, Earley W, Lu K, Hayes R, Laszlovszky I, Nemeth G. Efficacy of adjunctive low-dose cariprazine in major depressive disorder: a randomized, double-blind, placebo-controlled trial. Int Clin Psychopharmacol. 2018 Nov;33(6):312-321. doi: 10.1097/YIC.0000000000000235.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo
FG001	Cariprazine 0.1 - 0.3 mg	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine low dose

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

Montgomery-Asberg Depression Rating Scale (MADRS)

The patient is rated on a scale from 0-6 on 10 items. Apparent sadness, reported sadness, lassitude, pessimistic thoughts, inner tension, suicidal thoughts, reduced sleep and appetite, concentration difficulties, inability to feel. The overall MADRS score ranges from 0-60, with 0 meaning no symptoms and score of 60 meaning maximum severity. The primary efficacy parameter was the change in MADRS score totals from the scores taken at Baseline (Week 8) and during at least one more time point up to and including Week 16.

231 patients were randomized, and of them, 230 received at least 1 dose of treatment (Double-blind Safety Population), and had at least a baseline and 1 post-baseline MADRS assessment (Double-blind Intent To Treat Population). All patients in the Double-blind Intent To Treat Population were included in the efficacy analyses.

Posted

Least Squares Mean

Standard Error

Units on a Scale

Baseline (Week 8) to Week 16

ID	Title	Description
OG000	Placebo	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo
OG001	Cariprazine 0.1 - 0.3 mg	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine low dose
OG002	Cariprazine 1.0 - 2.0 mg	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine high dose

Units	Counts
Participants	OG00081 OG00176 OG00273

Title

Denominators

Categories

Title	Measurements
	OG000-8.0± 1.0 OG001-7.5± 1.1 OG002-9.8± 1.1

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		0.746		Least Squares Mean Difference	0.5			2-Sided	95	-2.4	3.4					Superiority
OG000 OG002		ANCOVA		0.227

Secondary

Clinical Global Impression - Improvement (CGI-I)

The Clinical Global Impression-Improvement (CGI-I) scale is a clinician rated scale that, in this study, will be used to rate total improvement or worsening of mental illness starting at Visit 2 (Week 2) and taken at every visit through Visit 11 (Week 16). The patient will be rated on a scale from 1 to 7, 1 indicating that the patient is very much improved and 7 indicating that the patient is very much worse. The secondary efficacy parameter was the CGI-I total score at Week 16.

Posted

Least Squares Mean

Standard Error

Units on a Scale

Week 16

ID	Title	Description
OG000	Placebo	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo
OG001	Cariprazine 0.1 - 0.3 mg	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine low dose
OG002	Cariprazine 1.0 - 2.0 mg

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	Prospective Antidepressant-Therapy Lead In Period	Interventions included: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) for 8 weeks prior to randomization	1	502	9	502	262	502
EG001	Placebo	Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo for 8 weeks. AE reporting covers this 8 week period plus the 30 day safety follow up that proceeds it.	0	81	1	81	32	81
EG002	Cariprazine 0.1 - 0.3 mg	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine low dose for 8 weeks. AE reporting covers this 8 week period plus the 30 day safety follow up that proceeds it.	0	76	0	76	29	76
EG003	Cariprazine 1.0 - 2.0 mg	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine high dose for 8 weeks. AE reporting covers this 8 week period plus the 30 day safety follow up that proceeds it.	0	73	1	73	35	73

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anxiety	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG0030 affected73 at risk
Hip Fracture	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Road Traffic Accident	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Upper Limb Fracture	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Suicidal Ideation	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Depression	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Convulsion	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Serotonin Syndrome	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Completed Suicide	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Intentional Overdose	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Alcohol Abuse	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Homicidal Ideation	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Suicide Attempt	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Angina Unstable	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected502 at risk EG0011 affected81 at risk EG0020 affected76 at risk EG003
Chronic Obstructive Pulmanary Disease	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG00073 affected502 at risk EG0013 affected81 at risk EG0028 affected76 at risk EG0036 affected73 at risk
Dizziness	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG00031 affected502 at risk EG0017 affected81 at risk EG0024 affected76 at risk EG003
Fatigue	General disorders	MedDRA 13.0	Systematic Assessment	EG00036 affected502 at risk EG0013 affected81 at risk EG0022 affected76 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG00060 affected502 at risk EG0013 affected81 at risk EG0022 affected76 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected502 at risk EG0015 affected81 at risk EG0021 affected76 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00070 affected502 at risk EG0015 affected81 at risk EG0025 affected76 at risk EG003
Dry Mouth	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00053 affected502 at risk EG0011 affected81 at risk EG0022 affected76 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00035 affected502 at risk EG0011 affected81 at risk EG0021 affected76 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00036 affected502 at risk EG0015 affected81 at risk EG0024 affected76 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG00029 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG00025 affected502 at risk EG0010 affected81 at risk EG0020 affected76 at risk EG003
Akathisia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected502 at risk EG0013 affected81 at risk EG0022 affected76 at risk EG003
Tremor	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected502 at risk EG0014 affected81 at risk EG0020 affected76 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected502 at risk EG0013 affected81 at risk EG0021 affected76 at risk EG003
Restlessness	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected502 at risk EG0011 affected81 at risk EG0021 affected76 at risk EG003
Increased appetite	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected502 at risk EG0011 affected81 at risk EG0021 affected76 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected502 at risk EG0011 affected81 at risk EG0024 affected76 at risk EG003

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

ID	Term
D011619	Psychotropic Drugs
D002491	Central Nervous System Agents
D045506	Therapeutic Uses
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses

ID	Title	Description
BG000	Placebo	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + Placebo
BG001	Cariprazine 0.1 - 0.3 mg	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR)+ cariprazine low dose
BG002	Cariprazine 1.0 - 2.0 mg	Drug: Antidepressant (citalopram, duloxetine, escitalopram, sertraline, or venlafaxine XR) + cariprazine high dose
BG003	Total	Total of all reporting groups