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Major Depressive Disorder (MDD) With Mixed Features - Flexible Dose (RESOLVE 1)

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ClinicalTrials.gov Identifier: NCT01421134
Recruitment Status : Completed
First Posted : August 22, 2011
Results First Posted : October 9, 2015
Last Update Posted : July 15, 2016
Sponsor:
Information provided by (Responsible Party):
Sunovion

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder With Mixed Features
Interventions Drug: Lurasidone
Drug: Placebo
Enrollment 211
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lurasidone Placebo
Hide Arm/Group Description

Lurasidone 20, 40 or 60 mg

Lurasidone: 20, 40, 60 mg, flexible dose, once daily PM 6 weeks

Placebo

Placebo: Placebo

Period Title: Overall Study
Started 109 102
Completed 102 87
Not Completed 7 15
Reason Not Completed
Adverse Event             3             5
Lack of Efficacy             2             4
Protocol Violation             0             3
Withdrawal by Subject             1             1
Administrative             0             1
Lost to Follow-up             1             1
Arm/Group Title Lurasidone Placebo Total
Hide Arm/Group Description

Lurasidone 20, 40 or 60 mg

Lurasidone: 20, 40, 60 mg, flexible dose, once daily PM 6 weeks

Placebo

Placebo: Placebo

Total of all reporting groups
Overall Number of Baseline Participants 109 100 209
Hide Baseline Analysis Population Description
Two subjects were randomized in error and were not treated.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants 100 participants 209 participants
<=18 years
1
   0.9%
0
   0.0%
1
   0.5%
Between 18 and 65 years
106
  97.2%
96
  96.0%
202
  96.7%
>=65 years
2
   1.8%
4
   4.0%
6
   2.9%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 109 participants 100 participants 209 participants
43.6  (12.08) 46.4  (12.01) 44.9  (12.10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants 100 participants 209 participants
Female
73
  67.0%
72
  72.0%
145
  69.4%
Male
36
  33.0%
28
  28.0%
64
  30.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants 100 participants 209 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   1.0%
1
   0.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
14
  12.8%
12
  12.0%
26
  12.4%
White
94
  86.2%
86
  86.0%
180
  86.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   0.9%
1
   1.0%
2
   1.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 109 participants 100 participants 209 participants
Russian Federation 18 13 31
United States 34 26 60
Ukraine 30 32 62
United Kingdom 1 3 4
Serbia 26 26 52
1.Primary Outcome
Title Mean Change From Baseline to the 6-week Study Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Scores
Hide Description The MADRS consists of 10 items, each rated on a Likert scale, from 0=”Normal” to 6=”Most Severe”. The MADRS total score is calculated as the sum of the 10 items. The MADRS total score ranges from 0 to 60. Higher scores are associated with greater severity.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population
Arm/Group Title Lurasidone Placebo
Hide Arm/Group Description:

Lurasidone 20, 40 or 60 mg

Lurasidone: 20, 40, 60 mg, flexible dose, once daily PM 6 weeks

Placebo

Placebo: Placebo

Overall Number of Participants Analyzed 108 100
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-20.5  (0.95) -13.0  (1.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lurasidone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -7.5
Confidence Interval (2-Sided) 95%
-10.2 to -4.8
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.37
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Change From Baseline to the 6-week Study Endpoint in the Clinical Global Impression-Severity of Illness (CGI-S) Score
Hide Description The CGI-S score is a single value, clinician-rated assessment of illness severity and ranges from 1= ‘Normal, not at all ill’ to 7= ‘Among the most extremely ill patients’. A higher score is associated with greater illness severity.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population
Arm/Group Title Lurasidone Placebo
Hide Arm/Group Description:

Lurasidone 20, 40 or 60 mg

Lurasidone: 20, 40, 60 mg, flexible dose, once daily PM 6 weeks

Placebo

Placebo: Placebo

Overall Number of Participants Analyzed 108 100
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.83  (0.109) -1.18  (0.115)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lurasidone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.65
Confidence Interval (2-Sided) 95%
-0.96 to -0.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.157
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change From Baseline to Week 6 in the Young Mania Rating Scale (YMRS) Total Score
Hide Description The YMRS is an 11-item clinician-rated instrument used to assess the severity of mania. Seven items are rated on a 5-point scale, ranging from 0 to 4, and four items are rated on a 9-point scale, ranging from 0 to 8. The YMRS total score is calculated as the sum of the 11 individual items and ranges from 0 to 60. Higher scores are associated with greater severity of mania.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population
Arm/Group Title Lurasidone Placebo
Hide Arm/Group Description:

Lurasidone 20, 40 or 60 mg

Lurasidone: 20, 40, 60 mg, flexible dose, once daily PM 6 weeks

Placebo

Placebo: Placebo

Overall Number of Participants Analyzed 108 100
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-7.0  (0.35) -4.9  (0.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lurasidone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-3.1 to -1.1
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.50
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline to Week 6 in the Sheehan Disability Scale (SDS) Total Score
Hide Description The SDS is a composite of three self-rated items designed to measure the extent to which three major sectors (work/school, social life/leisure, and family life/home responsibility) in the patient’s life are impaired by depressive symptoms. These three items are responded to on a visual analogue scale (VAS) ranging through 0 (no impairment), 1–3 (mild), 4–6 (moderate), 7–9 (marked) and 10 (extreme) disability. The SDS total score is calculated as the sum of the three items and ranges from 0 (unimpaired) to 30 (highly impaired).
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: If a subject has not worked/studied at all during the past week for reasons unrelated to the disorder, the SDS total score will be set to missing.
Arm/Group Title Lurasidone Placebo
Hide Arm/Group Description:

Lurasidone 20, 40 or 60 mg

Lurasidone: 20, 40, 60 mg, flexible dose, once daily PM 6 weeks

Placebo

Placebo: Placebo

Overall Number of Participants Analyzed 70 69
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-11.2  (0.88) -6.4  (0.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lurasidone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-7.2 to -2.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.21
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline to Week 6 in the Hamilton Rating Scale for Anxiety(HAM-A) Total Score
Hide Description The HAM-A is used to quantify the severity of anxiety symptomatology and consists of 14 items. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe/disabling). The HAM-A total score is calculated as the sum of the 14 individual items and ranges from 0 to 56. Higher scores are associated with greater degree of anxiety.
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population. 3 Lurasidone subjects and 2 placebo subjects did not have post-baseline HAM-A assessment.
Arm/Group Title Lurasidone Placebo
Hide Arm/Group Description:

Lurasidone 20, 40 or 60 mg

Lurasidone: 20, 40, 60 mg, flexible dose, once daily PM 6 weeks

Placebo

Placebo: Placebo

Overall Number of Participants Analyzed 105 98
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-9.9  (0.58) -5.4  (0.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lurasidone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -4.5
Confidence Interval (2-Sided) 95%
-6.1 to -2.9
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.81
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Subjects Who Achieve a Response, Defined as ≥ 50% Reduction From Baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 (LOCF).
Hide Description [Not Specified]
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population
Arm/Group Title Lurasidone Placebo
Hide Arm/Group Description:

Lurasidone 20, 40 or 60 mg

Lurasidone: 20, 40, 60 mg, flexible dose, once daily PM 6 weeks

Placebo

Placebo: Placebo

Overall Number of Participants Analyzed 108 100
Measure Type: Number
Unit of Measure: percentage of subjects
64.8 30.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lurasidone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.615
Confidence Interval (2-Sided) 95%
3.251 to 13.459
Estimation Comments Odds Ratio was based on a logistic regression of response, with treatment group, baseline MADRS total score, and pooled center as fixed effects.
7.Secondary Outcome
Title Percentage of Subjects Who Achieve a Remission, Defined as a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score of ≤ 12 at Week 6 (LOCF)
Hide Description [Not Specified]
Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population
Arm/Group Title Lurasidone Placebo
Hide Arm/Group Description:

Lurasidone 20, 40 or 60 mg

Lurasidone: 20, 40, 60 mg, flexible dose, once daily PM 6 weeks

Placebo

Placebo: Placebo

Overall Number of Participants Analyzed 108 100
Measure Type: Number
Unit of Measure: percentage of subjects
49.1 23.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lurasidone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.270
Confidence Interval (2-Sided) 95%
2.105 to 8.663
Estimation Comments [Not Specified]
Time Frame 6 Weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lurasidone Placebo
Hide Arm/Group Description

Lurasidone 20, 40 or 60 mg

Lurasidone: 20, 40, 60 mg, flexible dose, once daily PM 6 weeks

Placebo

Placebo: Placebo

All-Cause Mortality
Lurasidone Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Lurasidone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/109 (0.92%)      0/100 (0.00%)    
Psychiatric disorders     
Depression Suicidal  1  1/109 (0.92%)  1 0/100 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Lurasidone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   31/109 (28.44%)      29/100 (29.00%)    
Gastrointestinal disorders     
Nausea  1  7/109 (6.42%)  7 2/100 (2.00%)  2
Abdominal discomfort  1  4/109 (3.67%)  5 1/100 (1.00%)  1
Dry mouth  1  3/109 (2.75%)  3 1/100 (1.00%)  1
Infections and infestations     
Urinary Tract Infection  1  1/109 (0.92%)  1 2/100 (2.00%)  3
Injury, poisoning and procedural complications     
Contusion  1  0/109 (0.00%)  0 2/100 (2.00%)  2
Nervous system disorders     
Headache  1  6/109 (5.50%)  6 6/100 (6.00%)  7
Somnoelence  1  5/109 (4.59%)  6 1/100 (1.00%)  1
Akathisia  1  4/109 (3.67%)  4 2/100 (2.00%)  2
Dizziness  1  4/109 (3.67%)  5 3/100 (3.00%)  3
Psychiatric disorders     
Insomnia  1  6/109 (5.50%)  7 11/100 (11.00%)  11
Anxiety  1  4/109 (3.67%)  4 9/100 (9.00%)  12
Renal and urinary disorders     
Haemarturia  1  0/109 (0.00%)  0 2/100 (2.00%)  2
Skin and subcutaneous tissue disorders     
Pruritus  1  1/109 (0.92%)  1 2/100 (2.00%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
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.

There IS agreement between Principal Investigator and Sponsor that restricts PI's rights to discuss or publish trial results after trial is completed.

In addition to the <60-180 day restriction above, since this is a multicenter study, 1st publication of study results shall be made with other participating study sites as a multicenter publication provided, if a multicenter publication is not forthcoming within 24 months post completion of study at all sites, PI shall be free to publish.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: 1-866-503-6351
Organization: Sunovion
Phone: 1-866-503-6351
EMail: clinicaltrialdisclosure@sunvion.com
Layout table for additonal information
Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT01421134     History of Changes
Other Study ID Numbers: D1050304
First Submitted: August 17, 2011
First Posted: August 22, 2011
Results First Submitted: September 10, 2015
Results First Posted: October 9, 2015
Last Update Posted: July 15, 2016