Trial Outcomes & Findings for Safety and Efficacy of Levomilnacipran ER (F2695 SR) in Major Depressive Disorder (NCT NCT01034462)

Last Updated: 2013-10-25

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

442 participants

Primary outcome timeframe

From Baseline to Week 8

Results posted on

2013-10-25

Participant Flow

Patient were recruited over a 21-month period from December of 2009 to September of 2011 at 23 studies sites in the United States.

Patients went through a 1-week single-blind placebo run-in period immediately preceding an 8-week double-blind treatment period.

Participant milestones

Participant milestones
Measure	Placebo Matching placebo capsules, oral administration, once daily dosing for 8 weeks.	Levomilnacipran ER Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks.
Overall Study STARTED	217	217
Overall Study COMPLETED	172	163
Overall Study NOT COMPLETED	45	54

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo capsules, oral administration, once daily dosing for 8 weeks.	Levomilnacipran ER Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks.
Overall Study Adverse Event	7	17
Overall Study Lack of Efficacy	4	4
Overall Study Protocol Violation	10	7
Overall Study Withdrawal by Subject	9	8
Overall Study Lost to Follow-up	14	16
Overall Study Other reasons	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=217 Participants Matching placebo capsules, oral administration, once daily dosing for 8 weeks.	Levomilnacipran ER n=217 Participants Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks.	Total n=434 Participants Total of all reporting groups
Age Continuous	44.6 years STANDARD_DEVIATION 13.9 • n=5 Participants	45.0 years STANDARD_DEVIATION 13.2 • n=7 Participants	44.8 years STANDARD_DEVIATION 13.5 • n=5 Participants
Age, Customized 18 years to 19 years	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Age, Customized 20 years to 29 years	38 participants n=5 Participants	34 participants n=7 Participants	72 participants n=5 Participants
Age, Customized 30 years to 39 years	37 participants n=5 Participants	44 participants n=7 Participants	81 participants n=5 Participants
Age, Customized 40 years to 49 years	51 participants n=5 Participants	40 participants n=7 Participants	91 participants n=5 Participants
Age, Customized 50 years to 59 years	57 participants n=5 Participants	68 participants n=7 Participants	125 participants n=5 Participants
Age, Customized 60 years to 80 years	32 participants n=5 Participants	29 participants n=7 Participants	61 participants n=5 Participants
Sex: Female, Male Female	143 Participants n=5 Participants	140 Participants n=7 Participants	283 Participants n=5 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	77 Participants n=7 Participants	151 Participants n=5 Participants
Race/Ethnicity, Customized White	182 participants n=5 Participants	177 participants n=7 Participants	359 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	28 participants n=5 Participants	33 participants n=7 Participants	61 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska native	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Other	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	17 participants n=5 Participants	21 participants n=7 Participants	38 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	200 participants n=5 Participants	196 participants n=7 Participants	396 participants n=5 Participants
Region of Enrollment United States	217 participants n=5 Participants	217 participants n=7 Participants	434 participants n=5 Participants
Weight	84.58 kg STANDARD_DEVIATION 18.15 • n=5 Participants	84.47 kg STANDARD_DEVIATION 18.98 • n=7 Participants	84.52 kg STANDARD_DEVIATION 18.55 • n=5 Participants
Body Mass Index (BMI)	29.60 Kilograms Per Meter Squared STANDARD_DEVIATION 5.30 • n=5 Participants	29.20 Kilograms Per Meter Squared STANDARD_DEVIATION 5.45 • n=7 Participants	29.40 Kilograms Per Meter Squared STANDARD_DEVIATION 5.37 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 8

Population: The Safety Population consisted of 434 randomized patients who took at least 1 dose of double-blind investigational product. The Intent-to-Treat (ITT) Population consisted 429 patients in the Safety Population who had at least 1 postbaseline assessment of the MADRS total score.

Outcome measures

Outcome measures
Measure	Placebo n=214 Participants Matching placebo capsules, oral administration, once daily dosing. Placebo : Matching placebo to be given orally, in capsule form, once daily, for 8 weeks.	Levomilnacipran ER n=215 Participants Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	-12.2 units on a scale Standard Error 0.78	-15.3 units on a scale Standard Error 0.79

SECONDARY outcome

Timeframe: From Baseline to Week 8

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)

Outcome measures

Outcome measures
Measure	Placebo n=214 Participants Matching placebo capsules, oral administration, once daily dosing. Placebo : Matching placebo to be given orally, in capsule form, once daily, for 8 weeks.	Levomilnacipran ER n=215 Participants Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks
Change in Sheehan Disability Scale (SDS) Total Score	-5.4 units on a scale Standard Error 0.57	-8.0 units on a scale Standard Error 0.58

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 79 other events

Deaths: 0 deaths

Levomilnacipran ER

Serious events: 4 serious events

Other events: 151 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=217 participants at risk Matching placebo capsules, oral administration, once daily dosing for 8 weeks.	Levomilnacipran ER n=217 participants at risk Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks.
General disorders Non-cardiac chest pain	0.46% 1/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.46% 1/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Injury, poisoning and procedural complications Head injury	0.46% 1/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.46% 1/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Injury, poisoning and procedural complications Traumatic liver injury	0.46% 1/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Respiratory, thoracic and mediastinal disorders Asthma	0.46% 1/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.46% 1/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.46% 1/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Psychiatric disorders Suicide attempt	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.46% 1/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.46% 1/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Injury, poisoning and procedural complications Scratch	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.46% 1/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Vascular disorders Hypertension	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.92% 2/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Psychiatric disorders Suicidal ideation	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	0.92% 2/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.

Other adverse events

Other adverse events
Measure	Placebo n=217 participants at risk Matching placebo capsules, oral administration, once daily dosing for 8 weeks.	Levomilnacipran ER n=217 participants at risk Levomilnacipran ER capsules, flexible dose, oral administration, once daily dosing for 8 weeks.
Nervous system disorders Nausea	3.7% 8/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	21.7% 47/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Nervous system disorders Headache	12.4% 27/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	17.5% 38/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Nervous system disorders Dizziness	3.2% 7/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	12.9% 28/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Gastrointestinal disorders Dry mouth	11.1% 24/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	12.4% 27/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Gastrointestinal disorders Constipation	3.7% 8/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	10.1% 22/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Cardiac disorders Tachycardia	2.8% 6/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	8.3% 18/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Renal and urinary disorders Urinary hesitation	0.00% 0/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	7.8% 17/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.8% 4/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	6.9% 15/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Psychiatric disorders Insomnia	2.3% 5/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	6.9% 15/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Gastrointestinal disorders Diarrhoea	5.5% 12/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	6.5% 14/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Gastrointestinal disorders Vomiting	0.92% 2/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	6.5% 14/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Infections and infestations Upper respiratory tract infection	4.1% 9/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	6.0% 13/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.
Vascular disorders Hypertension	1.4% 3/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.	5.5% 12/217 • Adverse event data was collection over a 25-month period from December 2009 to January 2012 at 23 study sites in the U.S. 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.

Additional Information

Carl Gommoll, MS, Sr. Dir. Clinical Development Psychiatry

Forest Research Institute

Phone: 201-427-8000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER