Efficacy, Safety and Tolerability of Cariprazine as an Ad... | NCT01715805

Status Module

Name	Class
Gedeon Richter Ltd.	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo + ADT Lead-in	Other	Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks.	Drug: Placebo Drug: Antidepressant Therapy (ADT)
Placebo + ADT (Double-Blind)	Placebo Comparator	Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).	Drug: Placebo Drug: Antidepressant Therapy (ADT)
Cariprazine + ADT (Double-Blind)	Experimental	Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16).	Drug: Cariprazine Drug: Antidepressant Therapy (ADT)
Placebo + ADT (Continued Treatment)	Other	Following the 8 week ADT plus single blind placebo lead-in period, participants who were ADT responders continued treatment with ADT plus placebo for an additional 8 weeks.	Drug: Placebo Drug: Antidepressant Therapy (ADT)

Name	Type	Description	Arm Group Labels	Other Names
Cariprazine	Drug	Cariprazine capsules 1.5 to 4.5 mg/day	Cariprazine + ADT (Double-Blind)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline in the Double-Blind Period	The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Patients are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60.	Baseline (Week 8)
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in the Double-Blind Period	The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Participants are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60. A negative change from Baseline indicates improvement. Mixed-effects model for repeated measures (MMRM) with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses.	Baseline (Week 8) to Week 16

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Sheehan Disability Scale (SDS) Score in the Double-Blind Period	The Sheehan Disability Scale (SDS) is a 3-item patient-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum from 0 (no impairment) to 10 (most severe). The 3 individual scores are summed for a total possible score of 0 (unimpaired) to 30 (highly impaired). A negative change from Baseline indicates improvement. MMRM with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses.

Name	Affiliation	Role
Willie Earley, MD	Allergan	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Forest Investigative Site 032		Tucson	Arizona	85710	United States
Forest Investigative Site 018

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo + ADT Lead-in	Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks.
FG001	Placebo + ADT (Double-Blind)	Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).

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) at Baseline in the Double-Blind Period

The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Patients are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60.

Double-blind Intent-to-Treat (ITT) Population included all participants in the double-blind safety population who had a randomization baseline assessment and at least 1 postbaseline assessment of the MADRS total score during the double-blind treatment period.

Posted

Mean

Standard Deviation

score on a scale

Baseline (Week 8)

ID	Title	Description
OG000	Placebo + ADT (Double-Blind)	Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).
OG001	Cariprazine + ADT (Double-Blind)	Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16).

Units	Counts
Participants	OG000258 OG001267

Title

Denominators

Categories

Title	Measurements
	OG00025.2± 6.1 OG00125.4± 5.5

Primary

Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in the Double-Blind Period

The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Participants are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60. A negative change from Baseline indicates improvement. Mixed-effects model for repeated measures (MMRM) with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses.

Double-blind ITT Population included all participants in the double-blind safety population who had a randomization baseline assessment and at least 1 postbaseline assessment of the MADRS total score during the double-blind treatment period.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Week 8) to Week 16

ID	Title	Description
OG000	Placebo + ADT (Double-Blind)	Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).
OG001	Cariprazine + ADT (Double-Blind)

Secondary

Change From Baseline in Sheehan Disability Scale (SDS) Score in the Double-Blind Period

The Sheehan Disability Scale (SDS) is a 3-item patient-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum from 0 (no impairment) to 10 (most severe). The 3 individual scores are summed for a total possible score of 0 (unimpaired) to 30 (highly impaired). A negative change from Baseline indicates improvement. MMRM with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Week 8) to Week 16

ID	Title	Description
OG000	Placebo + ADT (Double-Blind)	Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).
OG001	Cariprazine + ADT (Double-Blind)	Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16).

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo + ADT Lead-in	Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks.	1,022	9	1,022	261	1,022
EG001	Placebo + ADT (Double-Blind)	Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).	258	3	258	50	258
EG002	Cariprazine + ADT (Double-Blind)	Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16).	269	1	269	101	269
EG003	Placebo + ADT (Continued Treatment)	Following the 8 week ADT plus single blind placebo lead-in period, participants who were ADT responders continued treatment with ADT plus placebo for an additional 8 weeks.	270	1	270	14	270

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Gastroenteritis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG0030 affected270 at risk
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG003
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG003
Traumatic liver injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG003
Syncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected1,022 at risk EG0010 affected258 at risk EG0021 affected269 at risk EG003
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 18.0	Systematic Assessment	EG0001 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG003
Migraine	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected1,022 at risk EG0011 affected258 at risk EG0020 affected269 at risk EG003
Seizure	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected1,022 at risk EG0011 affected258 at risk EG0020 affected269 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected1,022 at risk EG0011 affected258 at risk EG0020 affected269 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected1,022 at risk EG0011 affected258 at risk EG0020 affected269 at risk EG003
Depression	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected1,022 at risk EG0010 affected258 at risk EG0021 affected269 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected1,022 at risk EG0011 affected258 at risk EG0020 affected269 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00091 affected1,022 at risk EG00110 affected258 at risk EG00217 affected269 at risk EG0030 affected270 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00057 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected1,022 at risk EG0010 affected258 at risk EG0020 affected269 at risk EG003
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG00091 affected1,022 at risk EG00115 affected258 at risk EG00222 affected269 at risk EG003
Somnolence	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected1,022 at risk EG0013 affected258 at risk EG00214 affected269 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG00068 affected1,022 at risk EG00118 affected258 at risk EG00222 affected269 at risk EG003
Akathisia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected1,022 at risk EG0018 affected258 at risk EG00246 affected269 at risk EG003
Restlessness	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected1,022 at risk EG0015 affected258 at risk EG00223 affected269 at risk EG003

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders