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Trial record 15 of 1751 for:    depression AND Major Depression AND Scale | "Depression"

Safety and Efficacy of Levomilnacipran ER (Levomilnacipran SR) in Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT01377194
Recruitment Status : Completed
First Posted : June 21, 2011
Results First Posted : October 29, 2013
Last Update Posted : October 29, 2013
Sponsor:
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: Levomilnacipran ER
Drug: Placebo
Enrollment 568

Recruitment Details Patient recruitment occurred during a 6 month period from June to December 2011 at 47 study sites in the United States and 4 study sites in Canada.
Pre-assignment Details All patients went through a 1-week single-blind placebo run-in period before randomization.
Arm/Group Title Placebo Levomilnacipran ER 40 mg Levomilnacipran ER 80 mg
Hide Arm/Group Description Dose matched placebo, oral administration in capsule form, once daily for 8 weeks. 40mg of Levomilnacipran ER, oral administration in capsule form, once daily, for 8 weeks 80mg of Levomilnacipran ER, oral administration in capsule form, once daily, for 8 weeks
Period Title: Overall Study
Started 186 188 188
Completed 154 145 142
Not Completed 32 43 46
Reason Not Completed
Adverse Event             3             12             19
Lack of Efficacy             3             3             3
Protocol Violation             4             10             6
Withdrawal by Subject             8             10             7
Lost to Follow-up             14             8             11
Arm/Group Title Placebo Levomilnacipran ER 40 mg Levomilnacipran 80 mg Total
Hide Arm/Group Description Dose matched placebo, oral administration in capsule form, once daily for 8 weeks. 40mg Levomilnacipran ER, oral administration in capsule form, once daily for 8 weeks. 40mg Levomilnacipran ER, oral administration in capsule form, once daily for 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 186 188 188 562
Hide Baseline Analysis Population Description
The Baseline Participant population is based on the 562 randomized patients who went on to receive double-blind treatment (Safety Population).
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 186 participants 188 participants 188 participants 562 participants
42.3  (13.2) 42.9  (13.4) 43.1  (12.8) 42.8  (13.1)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 186 participants 188 participants 188 participants 562 participants
< 20 3 1 5 9
≥ 20-29 35 35 28 98
≥ 30-39 43 40 44 127
≥ 40-49 45 49 53 147
≥ 50-59 43 42 36 121
≥ 60 17 21 22 60
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 186 participants 188 participants 188 participants 562 participants
Female
116
  62.4%
117
  62.2%
124
  66.0%
357
  63.5%
Male
70
  37.6%
71
  37.8%
64
  34.0%
205
  36.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 186 participants 188 participants 188 participants 562 participants
White 135 142 139 416
Black or African-American 35 37 36 108
Asian 7 4 3 14
American Indian of Alaska Native 3 0 0 3
Native Hawaiian or other Pacific Islander 1 0 0 1
Other Race 5 5 10 20
Hispanic 23 24 15 62
Non-Hispanic 163 164 173 500
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 186 participants 188 participants 188 participants 562 participants
United States 177 183 180 540
Canada 9 5 8 22
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 186 participants 188 participants 188 participants 562 participants
81.60  (17.77) 81.35  (17.09) 81.73  (17.57) 81.56  (17.45)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 186 participants 188 participants 188 participants 562 participants
168.41  (9.69) 169.48  (9.79) 168.63  (8.91) 168.84  (9.47)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kilograms Per Meter Squared
Number Analyzed 186 participants 188 participants 188 participants 562 participants
28.67  (5.19) 28.25  (5.17) 28.71  (5.68) 28.54  (5.35)
1.Primary Outcome
Title Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score - Mixed-effects Model for Repeated Measures (MMRM) Analysis.
Hide Description The Montgomery-Asberg Depression Rating Scale (MADRS) rates patients 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 was scored on a 7-point scale. A score of 0 indicated the absence of symptoms, and a score of 6 indicated symptoms of maximum severity. The minimum overall score possible was 0 (absence of symptoms), with a maximum overall score of 60 (maximum severity).
Time Frame From Baseline to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 568 patients randomized to receive double-blind treatment, 562 patients received at least 1 dose of treatment and were included in the Safety Population, and 557 patients received at least 1 dose of treatment and had at least 1 postbaseline MADRS assessment and were included in the ITT Population.
Arm/Group Title Placebo Levomilnacipran ER 40 mg Levomilnacipran ER 80 mg
Hide Arm/Group Description:
Dose matched placebo oral administration in capsule form, once daily, for 8 weeks.
40mg Levomilnacipran ER oral administration in capsule form, once daily, for 8 weeks.
80mg of Levomilnacipran ER oral administration in capsule form, once daily for 8 weeks
Overall Number of Participants Analyzed 185 185 187
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-11.3  (0.77) -14.6  (0.79) -14.4  (0.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Levomilnacipran ER 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0027
Comments [Not Specified]
Method mixed-model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -3.303
Confidence Interval (2-Sided) 95%
-5.457 to -1.148
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Levomilnacipran ER 80 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0043
Comments [Not Specified]
Method mixed-model for repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -3.141
Confidence Interval (2-Sided) 95%
-5.293 to -0.988
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Sheehan Disability Scale (SDS) Total Score
Hide Description The Sheehan Disability Scale (SDS) is a 3-item clinician-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 (0 = no impairment to 10 = most severe) with the total SDS score ranging from 0 (no impairment) to 30 (most severe)
Time Frame From Baseline to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 568 patients randomized to receive double-blind treatment, 562 patients received at least 1 dose of treatment and were included in the Safety Population, and 557 patients received at least 1 dose of treatment and had at least 1 postbaseline MADRS assessment and were included in the ITT Population.
Arm/Group Title Placebo Levomilnacipran ER 40 mg Levomilnacipran ER 80 mg
Hide Arm/Group Description:
Dose matched placebo, oral administration in capsule form, once daily for 8 weeks.
40mg Levomilnacipran ER, oral administration in capsule form, once daily, for 8 weeks
80mg of Levomilnacipran ER, oral administration in capsule form, once daily, for 8 weeks
Overall Number of Participants Analyzed 185 185 187
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-5.4  (0.66) -7.3  (0.68) -8.2  (0.66)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Levomilnacipran ER 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0459
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed-effects model for repeated measures.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -1.827
Confidence Interval (2-Sided) 95%
-3.620 to -0.033
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Levomilnacipran ER 80 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0028
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed-effects model for repeated measures.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -2.720
Confidence Interval (2-Sided) 95%
-4.494 to -0.946
Estimation Comments [Not Specified]
Time Frame Adverse event data was collected over a 10 month period from June 2011 to March 2012.
Adverse Event Reporting Description The Serious Adverse Event data presented here is for the safety population. The Other Adverse Event data presented here is for the safety population during the 8 week double-blind treatment period.
 
Arm/Group Title Placebo Levomilnacipran ER 40 mg Levomilnacipran 80 mg
Hide Arm/Group Description Dose matched placebo, oral administration in capsule form, once daily for 8 weeks. 40mg Levomilnacipran ER, oral administration in capsule form, once daily for 8 weeks. 40mg Levomilnacipran ER, oral administration in capsule form, once daily for 8 weeks.
All-Cause Mortality
Placebo Levomilnacipran ER 40 mg Levomilnacipran 80 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Levomilnacipran ER 40 mg Levomilnacipran 80 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/186 (0.54%)   3/188 (1.60%)   0/188 (0.00%) 
Gastrointestinal disorders       
Intussusception  1  0/186 (0.00%)  1/188 (0.53%)  0/188 (0.00%) 
General disorders       
Non-cardiac chest pain  1  0/186 (0.00%)  1/188 (0.53%)  0/188 (0.00%) 
Injury, poisoning and procedural complications       
Facial Bones Fracture  1  1/186 (0.54%)  0/188 (0.00%)  0/188 (0.00%) 
Road traffic accident  1  1/186 (0.54%)  0/188 (0.00%)  0/188 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Asthma  1  0/186 (0.00%)  1/188 (0.53%)  0/188 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Levomilnacipran ER 40 mg Levomilnacipran 80 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   58/186 (31.18%)   90/188 (47.87%)   110/188 (58.51%) 
Cardiac disorders       
Tachycardia  1  6/186 (3.23%)  4/188 (2.13%)  15/188 (7.98%) 
Gastrointestinal disorders       
Nausea  1  11/186 (5.91%)  27/188 (14.36%)  29/188 (15.43%) 
Dry mouth  1  7/186 (3.76%)  19/188 (10.11%)  18/188 (9.57%) 
Constipation  1  4/186 (2.15%)  13/188 (6.91%)  12/188 (6.38%) 
Diarrhoea  1  10/186 (5.38%)  7/188 (3.72%)  7/188 (3.72%) 
Infections and infestations       
Upper respiratory tract infection  1  11/186 (5.91%)  10/188 (5.32%)  8/188 (4.26%) 
Investigations       
Heart rate increased  1  0/186 (0.00%)  13/188 (6.91%)  11/188 (5.85%) 
Nervous system disorders       
Headache  1  16/186 (8.60%)  22/188 (11.70%)  25/188 (13.30%) 
Dizziness  1  1/186 (0.54%)  7/188 (3.72%)  12/188 (6.38%) 
Renal and urinary disorders       
Urinary hesitation  1  0/186 (0.00%)  6/188 (3.19%)  12/188 (6.38%) 
Reproductive system and breast disorders       
Erectile dysfunction  1  1/70 (1.43%)  4/71 (5.63%)  9/64 (14.06%) 
Testicular pain  1  0/70 (0.00%)  3/71 (4.23%)  5/64 (7.81%) 
Skin and subcutaneous tissue disorders       
Hyperhidrosis  1  6/186 (3.23%)  4/188 (2.13%)  15/188 (7.98%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
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.

All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study.

Publication of the results by the PI will be patient to mutual agreement between the PI and Forest Research Institute, Inc.

Results Point of Contact
Name/Title: Carl Gommoll, MS, Sr. Dir. Clinical Development Psychiatry
Organization: Forest Research Institute
Phone: 201-427-8000 ext 8124
Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT01377194     History of Changes
Other Study ID Numbers: LVM-MD-10
First Submitted: June 10, 2011
First Posted: June 21, 2011
Results First Submitted: August 22, 2013
Results First Posted: October 29, 2013
Last Update Posted: October 29, 2013