Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 22 of 1901 for:    "Depressive Disorder" [DISEASE] AND Rating AND Major Depressive Disorder AND Depressive Disorder, Major

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00969709
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, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Levomilnacipran ER
Drug: Placebo
Enrollment 724
Recruitment Details Patient recruitment at 38 study centers located in the United States during a 17 month period from September 2009 to February 2011.
Pre-assignment Details The study included a 1-week, single-blind placebo run-in period immediately before the 8-week double-blind treatment period.
Arm/Group Title Placebo Levomilnacipran ER 40 mg Levomilnacipran ER 80 mg Levomilnacipran ER 120 mg
Hide Arm/Group Description

Dose matching placebo capsules, oral administration, once daily dosing.

Placebo : Matching placebo capsules, oral administration, once daily for 8 weeks.

40 mg/day Levomilnacipran ER capsules, low dose, oral administration, once daily dosing.

Levomilnacipran ER, low dose, oral administration, in capsule form, once daily for 8 weeks.

80 mg/day Levomilnacipran ER capsules, medium dose, oral administration, once daily dosing

Levomilnacipran ER, medium dose, oral administration, in capsule form, once daily for 8 weeks.

120 mg/day Levomilnacipran ER capsules, high dose, oral administration, once daily dosing

Levomilnacipran ER, high dose, oral administration, in capsule form, once daily for 8 weeks.

Period Title: Overall Study
Started 176 178 179 180
Completed 138 130 121 117
Not Completed 38 48 58 63
Reason Not Completed
Adverse Event             3             13             26             12
Lack of Efficacy             7             4             1             3
Protocol Violation             9             5             9             10
Withdrawal by Subject             9             12             11             23
Lost to Follow-up             10             14             8             15
Other reasons             0             0             3             0
Arm/Group Title Placebo Levomilnacipran ER 40 mg Levomilnacipran ER 80 mg Levomilnacipran ER 120 mg Total
Hide Arm/Group Description Dose matching placebo capsules, oral administration, once daily dosing for 8 weeks 40 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks. 80 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks. 120 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 176 178 179 180 713
Hide Baseline Analysis Population Description
A total of 724 patients were randomized to receive double-blind treatment (Randomized Population); 713 patients received at least 1 dose of treatment (Safety Population). The demographic analyses of the baseline participants is based on the Safety Population
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 176 participants 178 participants 179 participants 180 participants 713 participants
43.1  (11.3) 41.6  (13.1) 41.0  (12.8) 40.3  (11.9) 41.1  (12.3)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 176 participants 178 participants 179 participants 180 participants 713 participants
18 years to 19 years 1 2 4 2 9
20 years to 29 years 31 43 44 42 160
30 years to 39 years 47 34 33 38 152
40 years to 49 years 44 36 48 46 174
50 years to 59 years 46 48 36 41 171
60 years to 65 years 7 15 14 11 47
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants 178 participants 179 participants 180 participants 713 participants
Female
108
  61.4%
122
  68.5%
111
  62.0%
106
  58.9%
447
  62.7%
Male
68
  38.6%
56
  31.5%
68
  38.0%
74
  41.1%
266
  37.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 176 participants 178 participants 179 participants 180 participants 713 participants
White 134 133 129 130 526
Black or African American 29 36 39 41 145
Asian 8 3 5 3 19
American Indian or Alaska native 1 0 2 1 4
Native Hawaiian or other Pacific Islander 0 0 0 1 1
Other 3 6 4 4 17
Hispanic or Latino 20 22 28 22 92
Not Hispanic or Latino 156 155 151 158 620
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 176 participants 178 participants 179 participants 180 participants 713 participants
176 178 179 180 713
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 176 participants 178 participants 179 participants 180 participants 713 participants
83.8  (19.3) 79.5  (17.1) 83.0  (17.3) 84.2  (18.6) 82.6  (18.1)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kilograms Per Meter Squared
Number Analyzed 176 participants 178 participants 179 participants 180 participants 713 participants
29.0  (5.8) 28.0  (5.3) 28.9  (5.4) 29.2  (5.4) 28.8  (5.5)
1.Primary Outcome
Title Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Hide Description

The 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 for all measured symptoms).

Time Frame From Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
A total of 724 patients were randomized to receive double-blind treatment (Randomized Population); 713 patients received at least 1 dose of treatment (Safety Population); and 704 patients received at least 1 dose of treatment and had at least 1 postbaseline MADRS-CR assessment (Intent to Treat [ITT] Population).
Arm/Group Title Placebo Levomilnacipran ER 40 mg Levomilnacipran ER 80 mg Levomilnacipran ER 120 mg
Hide Arm/Group Description:

Dose matching placebo capsules, oral administration, once daily dosing.

Placebo : Matching placebo capsules, oral administration, once daily for 8 weeks.

40 mg/day Levomilnacipran ER capsules, low dose, oral administration, once daily dosing.

Levomilnacipran ER, low dose, oral administration, in capsule form, once daily for 8 weeks.

80 mg/day Levomilnacipran ER capsules, medium dose, oral administration, once daily dosing

Levomilnacipran ER, medium dose, oral administration, in capsule form, once daily for 8 weeks.

120 mg/day Levomilnacipran ER capsules, high dose, oral administration, once daily dosing

Levomilnacipran ER, high dose, oral administration, in capsule form, once daily for 8 weeks.

Overall Number of Participants Analyzed 175 176 177 176
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-11.6  (0.97) -14.8  (0.99) -15.6  (1.00) -16.5  (1.02)
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 0.0186
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 -3.23
Confidence Interval (2-Sided) 95%
-5.92 to -0.54
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 0.0038
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 -3.99
Confidence Interval (2-Sided) 95%
-6.69 to -1.29
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Levomilnacipran ER 120 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
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 -4.86
Confidence Interval (2-Sided) 95%
-7.59 to -2.12
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Sheehan Disability Scale (SDS) Total Score
Time Frame From Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
A total of 724 patients were randomized to receive double-blind treatment (Randomized Population); 713 patients received at least 1 dose of treatment (Safety Population); and 704 patients received at least 1 dose of treatment and had at least 1 postbaseline MADRS-CR assessment(Intent to Treat [ITT] Population).
Arm/Group Title Placebo Levomilnacipran ER 40 mg Levomilnacipran ER 80 mg Levomilnacipran ER 120 mg
Hide Arm/Group Description:
Dose matching placebo capsules, oral administration, once daily dosing for 8 weeks
40 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks.
80 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks.
120 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks.
Overall Number of Participants Analyzed 175 176 177 176
Mean (Standard Error)
Unit of Measure: units on a scale
-7.2  (0.74) -8.6  (0.75) -9.7  (0.77) -9.7  (0.78)
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 0.1687
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 -1.41
Confidence Interval (2-Sided) 95%
-3.42 to 0.60
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 0.0151
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 -2.51
Confidence Interval (2-Sided) 95%
-4.54 to -0.49
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Levomilnacipran ER 120 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0141
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 -2.57
Confidence Interval (2-Sided) 95%
-4.62 to -0.52
Estimation Comments [Not Specified]
Time Frame Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites.
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 ER 80 mg Levomilnacipran ER 120 mg
Hide Arm/Group Description Dose matching placebo capsules, oral administration, once daily dosing for 8 weeks. 40 mg per day Levomilnacipran ER, low dose, oral administration, once daily for 8 weeks. 80 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks. 120 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks.
All-Cause Mortality
Placebo Levomilnacipran ER 40 mg Levomilnacipran ER 80 mg Levomilnacipran ER 120 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Levomilnacipran ER 40 mg Levomilnacipran ER 80 mg Levomilnacipran ER 120 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/176 (0.57%)   3/178 (1.69%)   2/179 (1.12%)   1/180 (0.56%) 
General disorders         
Chest Pain  1  0/176 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/180 (0.00%) 
Infections and infestations         
Cytomegalovirus mononucleosis  1  0/176 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/180 (0.00%) 
Pneumonia  1  1/176 (0.57%)  0/178 (0.00%)  0/179 (0.00%)  0/180 (0.00%) 
Pregnancy, puerperium and perinatal conditions         
Premature baby  1  0/108 (0.00%)  0/122 (0.00%)  0/111 (0.00%)  1/106 (0.94%) 
Small for dates baby  1  0/108 (0.00%)  0/122 (0.00%)  0/111 (0.00%)  1/106 (0.94%) 
Pre-eclampsia  1  0/108 (0.00%)  0/122 (0.00%)  1/111 (0.90%)  0/106 (0.00%) 
Psychiatric disorders         
Aggression  1  0/176 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/180 (0.00%) 
Suicide Attempt  1  0/176 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/180 (0.00%) 
Vascular disorders         
Deep vein thrombosis  1  0/176 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/180 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
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 ER 80 mg Levomilnacipran ER 120 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   66/176 (37.50%)   110/178 (61.80%)   122/179 (68.16%)   112/180 (62.22%) 
Cardiac disorders         
Palpitations  1  1/176 (0.57%)  8/178 (4.49%)  11/179 (6.15%)  8/180 (4.44%) 
Tachycardia  1  0/176 (0.00%)  4/178 (2.25%)  11/179 (6.15%)  3/180 (1.67%) 
Gastrointestinal disorders         
Nausea  1  4/176 (2.27%)  19/178 (10.67%)  39/179 (21.79%)  23/180 (12.78%) 
Constipation  1  7/176 (3.98%)  19/178 (10.67%)  18/179 (10.06%)  23/180 (12.78%) 
Dry mouth  1  17/176 (9.66%)  20/178 (11.24%)  12/179 (6.70%)  27/180 (15.00%) 
Vomiting  1  0/176 (0.00%)  10/178 (5.62%)  10/179 (5.59%)  6/180 (3.33%) 
Diarrhoea  1  3/176 (1.70%)  8/178 (4.49%)  7/179 (3.91%)  7/180 (3.89%) 
Infections and infestations         
Upper respiratory tract infection  1  10/176 (5.68%)  14/178 (7.87%)  11/179 (6.15%)  4/180 (2.22%) 
Nasopharyngitis  1  10/176 (5.68%)  11/178 (6.18%)  9/179 (5.03%)  7/180 (3.89%) 
Investigations         
Heart rate increased  1  3/176 (1.70%)  18/178 (10.11%)  11/179 (6.15%)  17/180 (9.44%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  7/176 (3.98%)  2/178 (1.12%)  9/179 (5.03%)  7/180 (3.89%) 
Nervous system disorders         
Headache  1  20/176 (11.36%)  29/178 (16.29%)  36/179 (20.11%)  27/180 (15.00%) 
Dizziness  1  8/176 (4.55%)  10/178 (5.62%)  17/179 (9.50%)  14/180 (7.78%) 
Psychiatric disorders         
Insomnia  1  7/176 (3.98%)  7/178 (3.93%)  11/179 (6.15%)  7/180 (3.89%) 
Renal and urinary disorders         
Urinary hesitation  1  0/176 (0.00%)  7/178 (3.93%)  6/179 (3.35%)  11/180 (6.11%) 
Reproductive system and breast disorders         
Erectile dysfunction  1  2/68 (2.94%)  3/56 (5.36%)  2/68 (2.94%)  7/74 (9.46%) 
Ejaculation delayed  1  0/68 (0.00%)  0/56 (0.00%)  4/68 (5.88%)  0/74 (0.00%) 
Skin and subcutaneous tissue disorders         
Hyperhidrosis  1  4/176 (2.27%)  9/178 (5.06%)  24/179 (13.41%)  10/180 (5.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
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 Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Carl Gommoll, MS, Sr. Dir. Clinical Development Psychiatry
Organization: Forest Research Institute
Phone: 201-427-8000 ext 8124
EMail: carl.gommoll@frx.com
Layout table for additonal information
Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT00969709     History of Changes
Other Study ID Numbers: LVM-MD-01
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