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Safety and Efficacy of Levomilnacipran ER (F2695 SR) in Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT00969150
Recruitment Status : Completed
First Posted : September 1, 2009
Results First Posted : October 25, 2013
Last Update Posted : October 25, 2013
Sponsor:
Information provided by (Responsible Party):
Forest Laboratories

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Levomilnacipran ER
Drug: Placebo
Enrollment 362

Recruitment Details Patient were recruited over a 12-month period from September of 2009 to September of 2010 at 24 studies sites in the United States.
Pre-assignment Details Patients went through a 1-week single-blind placebo run-in period immediately preceding an 8-week double-blind treatment period.
Arm/Group Title Placebo Levomilnacipran ER
Hide Arm/Group Description Dose Matched placebo capsules, oral administration, once daily dosing for 8 weeks. Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks.
Period Title: Overall Study
Started 182 175
Completed 149 135
Not Completed 33 40
Reason Not Completed
Adverse Event             4             14
Lack of Efficacy             1             1
Protocol Violation             9             12
Withdrawal by Subject             13             9
Lost to Follow-up             5             4
Other reasons             1             0
Arm/Group Title Placebo Levomilnacipran ER Total
Hide Arm/Group Description Matching placebo capsules, oral administration, once daily dosing for 8 weeks. Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 182 175 357
Hide Baseline Analysis Population Description
While a total of 362 patients were randomized to receive double-blind treatment, 5 of these patients were either lost to follow up or withdrew consent before receiving double-blind treatment. The Baseline Participant population is based on the 357 randomized patients who went on to receive double-blind treatment (Safety Population).
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 182 participants 175 participants 357 participants
43.7  (13.3) 42.8  (12.9) 43.3  (13.1)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 182 participants 175 participants 357 participants
18 years to 19 years 2 1 3
20 years to 29 years 33 34 67
30 years to 39 years 35 32 67
40 years to 49 years 47 53 100
50 years to 59 years 40 37 77
60 years to 80 years 25 18 43
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 182 participants 175 participants 357 participants
Female
116
  63.7%
99
  56.6%
215
  60.2%
Male
66
  36.3%
76
  43.4%
142
  39.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 182 participants 175 participants 357 participants
White 149 133 282
Black or African American 28 29 57
Asian 3 4 7
American Indian or Alaska native 0 3 3
Other 2 6 8
Hispanic or Latino 18 16 34
Not Hispanic or Latino 164 159 323
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 182 participants 175 participants 357 participants
182 175 357
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 182 participants 175 participants 357 participants
82.9  (18.0) 82.4  (18.1) 82.7  (18.0)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kilograms Per Meter Squared
Number Analyzed 182 participants 175 participants 357 participants
28.9  (5.7) 28.7  (5.4) 28.8  (5.5)
1.Primary Outcome
Title Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Hide Description

MADRS was used 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 of the 10 items are 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. The total MADRS score for this measure ranges from 0 (absence of symptoms) to 60 (maximum severity).

Time Frame From Baseline to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 357 patients who received at least 1 dose of double-blind treatment (Safety Population), 355 patients had at least 1 postbaseline MADRS assessment (Intent to Treat [ITT] Population).
Arm/Group Title Placebo Levomilnacipran ER
Hide Arm/Group Description:
Matching placebo capsules, oral administration, once daily dosing for 8 weeks.
Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks.
Overall Number of Participants Analyzed 181 174
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-14.2  (0.90) -15.7  (0.94)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Levomilnacipran ER
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2492
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 -1.49
Confidence Interval (2-Sided) 95%
-4.02 to 1.05
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Sheehan Disability Scale (SDS) Total Score
Time Frame From Baseline to Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Levomilnacipran ER
Hide Arm/Group Description:
Matching placebo capsules, oral administration, once daily dosing for 8 weeks.
Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks.
Overall Number of Participants Analyzed 181 174
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-8.2  (0.67) -8.8  (0.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Levomilnacipran ER
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5625
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 -0.54
Confidence Interval (2-Sided) 95%
-2.38 to 1.29
Estimation Comments [Not Specified]
Time Frame Adverse event data was collection over a 14-month period from September 2009 to November 2010 at 24 study sites in the U.S.
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
Hide Arm/Group Description Matching placebo capsules, oral administration, once daily dosing for 8 weeks. Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks.
All-Cause Mortality
Placebo Levomilnacipran ER
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Levomilnacipran ER
Affected / at Risk (%) Affected / at Risk (%)
Total   1/182 (0.55%)   0/175 (0.00%) 
General disorders     
Chest Pain  1  1/182 (0.55%)  0/175 (0.00%) 
Investigations     
Blood Pressure Increased  1  1/182 (0.55%)  0/175 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
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
Affected / at Risk (%) Affected / at Risk (%)
Total   58/182 (31.87%)   90/175 (51.43%) 
Gastrointestinal disorders     
Nausea  1  6/182 (3.30%)  30/175 (17.14%) 
Dry mouth  1  11/182 (6.04%)  14/175 (8.00%) 
Vomiting  1  1/182 (0.55%)  10/175 (5.71%) 
Infections and infestations     
Upper respiratory tract infection  1  11/182 (6.04%)  6/175 (3.43%) 
Investigations     
Heart rate increased  1  4/182 (2.20%)  9/175 (5.14%) 
Nervous system disorders     
Headache  1  22/182 (12.09%)  28/175 (16.00%) 
Dizziness  1  3/182 (1.65%)  11/175 (6.29%) 
Psychiatric disorders     
Insomnia  1  13/182 (7.14%)  12/175 (6.86%) 
Reproductive system and breast disorders     
Ejaculation disorder  1  0/66 (0.00%)  6/76 (7.89%) 
Erectile dysfunction  1  1/66 (1.52%)  4/76 (5.26%) 
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  2/182 (1.10%)  12/175 (6.86%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
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.

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 Investigator will be subject to mutual agreement between the Investigator 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: NCT00969150     History of Changes
Other Study ID Numbers: LVM-MD-02
First Submitted: August 31, 2009
First Posted: September 1, 2009
Results First Submitted: August 22, 2013
Results First Posted: October 25, 2013
Last Update Posted: October 25, 2013