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Trial record 87 of 89 for:    DESVENLAFAXINE

Efficacy, Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy (ADT) in Patients With Major Depressive Disorder (MDD)

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ClinicalTrials.gov Identifier: NCT01715805
Recruitment Status : Completed
First Posted : October 29, 2012
Results First Posted : August 26, 2019
Last Update Posted : August 26, 2019
Sponsor:
Collaborator:
Gedeon Richter Ltd.
Information provided by (Responsible Party):
Forest Laboratories

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Cariprazine
Drug: Placebo
Drug: Antidepressant Therapy (ADT)
Enrollment 1022
Recruitment Details  
Pre-assignment Details 1022 patients participated in an 8 week open label antidepression therapy (ADT) + single blind placebo lead-in period. 530 patients who did not respond were randomized to receive ADT or cariprazine + ADT in the double-blind period and non-responders continued ADT + Placebo.
Arm/Group Title Placebo + ADT Lead-in Placebo + ADT (Double-Blind) Cariprazine + ADT (Double-Blind) Placebo + ADT (Continued Treatment)
Hide Arm/Group Description Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks. 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). 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). 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.
Period Title: Placebo + ADT Lead-in Period
Started 1022 0 0 0
Completed 807 0 0 0
Not Completed 215 0 0 0
Reason Not Completed
Adverse Event             41             0             0             0
Insufficient therapeutic response             6             0             0             0
Protocol Violation             74             0             0             0
Withdrawal of Consent             49             0             0             0
Lost to Follow-up             34             0             0             0
Site Terminated by Sponsor             1             0             0             0
Other Reason Not Specified             10             0             0             0
Period Title: Double-Blind or Continued Treatment
Started 0 261 269 270
Double-Blind Safety Population 0 258 269 0
Completed 0 222 213 222
Not Completed 0 39 56 48
Reason Not Completed
Study or Site Terminated by Sponsor             0             0             0             1
Adverse Event             0             3             23             2
Protocol Violation             0             14             12             19
Withdrawal of consent             0             11             11             13
Lost to Follow-up             0             7             10             10
Other Reason Not Specified             0             1             0             3
Did not ingest Double-Blind Treatment             0             3             0             0
Arm/Group Title Placebo + ADT Lead-in
Hide Arm/Group Description Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks.
Overall Number of Baseline Participants 1022
Hide Baseline Analysis Population Description
Pre-Randomization Safety Population included all patients in the screened population who took at least 1 dose of prospective open-label ADT plus single-blind placebo during the prospective ADT lead-in period of the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1022 participants
44.1  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1022 participants
Female
673
  65.9%
Male
349
  34.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 1022 participants
White
741
  72.5%
Black or African American
250
  24.5%
Asian
18
   1.8%
American Indian or Alaska Native
8
   0.8%
Native Hawaiian or Other Pacific Islander
3
   0.3%
Other
2
   0.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Ethnicity Number Analyzed 1022 participants
Hispanic or Latino
234
  22.9%
Not Hispanic or Latino
788
  77.1%
1.Primary Outcome
Title Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline in the Double-Blind Period
Hide Description 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.
Time Frame Baseline (Week 8)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + ADT (Double-Blind) Cariprazine + ADT (Double-Blind)
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 258 267
Mean (Standard Deviation)
Unit of Measure: score on a scale
25.2  (6.1) 25.4  (5.5)
2.Primary Outcome
Title Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in the Double-Blind Period
Hide Description 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.
Time Frame Baseline (Week 8) to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + ADT (Double-Blind) Cariprazine + ADT (Double-Blind)
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 258 267
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-7.5  (0.5) -7.7  (0.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + ADT (Double-Blind), Cariprazine + ADT (Double-Blind)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7948
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference (LSMD)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.6 to 1.2
Estimation Comments Cariprazine + ADT - Placebo + ADT
3.Secondary Outcome
Title Change From Baseline in Sheehan Disability Scale (SDS) Score in the Double-Blind Period
Hide Description 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.
Time Frame Baseline (Week 8) to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + ADT (Double-Blind) Cariprazine + ADT (Double-Blind)
Hide Arm/Group Description:
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).
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).
Overall Number of Participants Analyzed 258 267
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-3.1  (0.5) -3.7  (0.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + ADT (Double-Blind), Cariprazine + ADT (Double-Blind)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2784
Comments 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.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LSMD
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.9 to 0.5
Estimation Comments Cariprazine +ADT - Placebo + ADT
Time Frame First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms
Adverse Event Reporting Description Other Adverse Events at a threshold of >=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.
 
Arm/Group Title Placebo + ADT Lead-in Placebo + ADT (Double-Blind) Cariprazine + ADT (Double-Blind) Placebo + ADT (Continued Treatment)
Hide Arm/Group Description Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks. 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). 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). 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.
All-Cause Mortality
Placebo + ADT Lead-in Placebo + ADT (Double-Blind) Cariprazine + ADT (Double-Blind) Placebo + ADT (Continued Treatment)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/1022 (0.00%)   0/258 (0.00%)   0/269 (0.00%)   0/270 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo + ADT Lead-in Placebo + ADT (Double-Blind) Cariprazine + ADT (Double-Blind) Placebo + ADT (Continued Treatment)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/1022 (0.88%)   3/258 (1.16%)   1/269 (0.37%)   1/270 (0.37%) 
Gastrointestinal disorders         
Pancreatitis acute  1  0/1022 (0.00%)  1/258 (0.39%)  0/269 (0.00%)  0/270 (0.00%) 
Hepatobiliary disorders         
Cholecystitis  1  1/1022 (0.10%)  0/258 (0.00%)  0/269 (0.00%)  0/270 (0.00%) 
Cholelithiasis  1  0/1022 (0.00%)  1/258 (0.39%)  0/269 (0.00%)  0/270 (0.00%) 
Infections and infestations         
Gastroenteritis  1  1/1022 (0.10%)  0/258 (0.00%)  0/269 (0.00%)  0/270 (0.00%) 
Pneumonia  1  1/1022 (0.10%)  0/258 (0.00%)  0/269 (0.00%)  0/270 (0.00%) 
Injury, poisoning and procedural complications         
Fall  1  1/1022 (0.10%)  0/258 (0.00%)  0/269 (0.00%)  0/270 (0.00%) 
Lower limb fracture  1  1/1022 (0.10%)  0/258 (0.00%)  0/269 (0.00%)  0/270 (0.00%) 
Traumatic liver injury  1  1/1022 (0.10%)  0/258 (0.00%)  0/269 (0.00%)  0/270 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Breast cancer  1  1/1022 (0.10%)  0/258 (0.00%)  0/269 (0.00%)  0/270 (0.00%) 
Nervous system disorders         
Syncope  1  1/1022 (0.10%)  0/258 (0.00%)  0/269 (0.00%)  0/270 (0.00%) 
Migraine  1  0/1022 (0.00%)  1/258 (0.39%)  0/269 (0.00%)  0/270 (0.00%) 
Seizure  1  0/1022 (0.00%)  1/258 (0.39%)  0/269 (0.00%)  0/270 (0.00%) 
Pregnancy, puerperium and perinatal conditions         
Abortion spontaneous  1  1/1022 (0.10%)  0/258 (0.00%)  0/269 (0.00%)  0/270 (0.00%) 
Psychiatric disorders         
Suicidal ideation  1  1/1022 (0.10%)  0/258 (0.00%)  1/269 (0.37%)  0/270 (0.00%) 
Depression  1  0/1022 (0.00%)  0/258 (0.00%)  1/269 (0.37%)  0/270 (0.00%) 
Confusional state  1  0/1022 (0.00%)  0/258 (0.00%)  0/269 (0.00%)  1/270 (0.37%) 
Respiratory, thoracic and mediastinal disorders         
Pulmonary embolism  1  0/1022 (0.00%)  1/258 (0.39%)  0/269 (0.00%)  0/270 (0.00%) 
1
Term from vocabulary, MedDRA 18.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + ADT Lead-in Placebo + ADT (Double-Blind) Cariprazine + ADT (Double-Blind) Placebo + ADT (Continued Treatment)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   261/1022 (25.54%)   50/258 (19.38%)   101/269 (37.55%)   14/270 (5.19%) 
Gastrointestinal disorders         
Nausea  1  91/1022 (8.90%)  10/258 (3.88%)  17/269 (6.32%)  0/270 (0.00%) 
Diarrhoea  1  57/1022 (5.58%)  0/258 (0.00%)  0/269 (0.00%)  0/270 (0.00%) 
Infections and infestations         
Nasopharyngitis  1  0/1022 (0.00%)  0/258 (0.00%)  0/269 (0.00%)  14/270 (5.19%) 
Nervous system disorders         
Headache  1  91/1022 (8.90%)  15/258 (5.81%)  22/269 (8.18%)  0/270 (0.00%) 
Somnolence  1  0/1022 (0.00%)  3/258 (1.16%)  14/269 (5.20%)  0/270 (0.00%) 
Akathisia  1  0/1022 (0.00%)  8/258 (3.10%)  46/269 (17.10%)  0/270 (0.00%) 
Psychiatric disorders         
Insomnia  1  68/1022 (6.65%)  18/258 (6.98%)  22/269 (8.18%)  0/270 (0.00%) 
Restlessness  1  0/1022 (0.00%)  5/258 (1.94%)  23/269 (8.55%)  0/270 (0.00%) 
1
Term from vocabulary, MedDRA 18.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area, Head
Organization: Allergan
Phone: 714-246-4500
EMail: clinicaltrials@allergan.com
Layout table for additonal information
Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT01715805     History of Changes
Other Study ID Numbers: RGH-MD-72
First Submitted: October 25, 2012
First Posted: October 29, 2012
Results First Submitted: July 29, 2019
Results First Posted: August 26, 2019
Last Update Posted: August 26, 2019