Trial Outcomes & Findings for Safety and Efficacy of Levomilnacipran ER (F2695 SR) in Major Depressive Disorder (NCT NCT00969709)

Last Updated: 2013-10-25

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

724 participants

Primary outcome timeframe

From Baseline to Week 8

Results posted on

2013-10-25

Participant Flow

Patient recruitment at 38 study centers located in the United States during a 17 month period from September 2009 to February 2011.

The study included a 1-week, single-blind placebo run-in period immediately before the 8-week double-blind treatment period.

Participant milestones

Participant milestones
Measure	Placebo Dose matching placebo capsules, oral administration, once daily dosing. Placebo : Matching placebo capsules, oral administration, once daily for 8 weeks.	Levomilnacipran ER 40 mg 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.	Levomilnacipran ER 80 mg 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.	Levomilnacipran ER 120 mg 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 Study STARTED	176	178	179	180
Overall Study COMPLETED	138	130	121	117
Overall Study NOT COMPLETED	38	48	58	63

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Dose matching placebo capsules, oral administration, once daily dosing. Placebo : Matching placebo capsules, oral administration, once daily for 8 weeks.	Levomilnacipran ER 40 mg 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.	Levomilnacipran ER 80 mg 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.	Levomilnacipran ER 120 mg 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 Study Adverse Event	3	13	26	12
Overall Study Lack of Efficacy	7	4	1	3
Overall Study Protocol Violation	9	5	9	10
Overall Study Withdrawal by Subject	9	12	11	23
Overall Study Lost to Follow-up	10	14	8	15
Overall Study Other reasons	0	0	3	0

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=176 Participants Dose matching placebo capsules, oral administration, once daily dosing for 8 weeks	Levomilnacipran ER 40 mg n=178 Participants 40 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks.	Levomilnacipran ER 80 mg n=179 Participants 80 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks.	Levomilnacipran ER 120 mg n=180 Participants 120 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks.	Total n=713 Participants Total of all reporting groups
Weight	83.8 kg STANDARD_DEVIATION 19.3 • n=5 Participants	79.5 kg STANDARD_DEVIATION 17.1 • n=7 Participants	83.0 kg STANDARD_DEVIATION 17.3 • n=5 Participants	84.2 kg STANDARD_DEVIATION 18.6 • n=4 Participants	82.6 kg STANDARD_DEVIATION 18.1 • n=21 Participants
Body Mass Index (BMI)	29.0 Kilograms Per Meter Squared STANDARD_DEVIATION 5.8 • n=5 Participants	28.0 Kilograms Per Meter Squared STANDARD_DEVIATION 5.3 • n=7 Participants	28.9 Kilograms Per Meter Squared STANDARD_DEVIATION 5.4 • n=5 Participants	29.2 Kilograms Per Meter Squared STANDARD_DEVIATION 5.4 • n=4 Participants	28.8 Kilograms Per Meter Squared STANDARD_DEVIATION 5.5 • n=21 Participants
Age Continuous	43.1 years STANDARD_DEVIATION 11.3 • n=5 Participants	41.6 years STANDARD_DEVIATION 13.1 • n=7 Participants	41.0 years STANDARD_DEVIATION 12.8 • n=5 Participants	40.3 years STANDARD_DEVIATION 11.9 • n=4 Participants	41.1 years STANDARD_DEVIATION 12.3 • n=21 Participants
Age, Customized 18 years to 19 years	1 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	2 participants n=4 Participants	9 participants n=21 Participants
Age, Customized 20 years to 29 years	31 participants n=5 Participants	43 participants n=7 Participants	44 participants n=5 Participants	42 participants n=4 Participants	160 participants n=21 Participants
Age, Customized 30 years to 39 years	47 participants n=5 Participants	34 participants n=7 Participants	33 participants n=5 Participants	38 participants n=4 Participants	152 participants n=21 Participants
Age, Customized 40 years to 49 years	44 participants n=5 Participants	36 participants n=7 Participants	48 participants n=5 Participants	46 participants n=4 Participants	174 participants n=21 Participants
Age, Customized 50 years to 59 years	46 participants n=5 Participants	48 participants n=7 Participants	36 participants n=5 Participants	41 participants n=4 Participants	171 participants n=21 Participants
Age, Customized 60 years to 65 years	7 participants n=5 Participants	15 participants n=7 Participants	14 participants n=5 Participants	11 participants n=4 Participants	47 participants n=21 Participants
Sex: Female, Male Female	108 Participants n=5 Participants	122 Participants n=7 Participants	111 Participants n=5 Participants	106 Participants n=4 Participants	447 Participants n=21 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	56 Participants n=7 Participants	68 Participants n=5 Participants	74 Participants n=4 Participants	266 Participants n=21 Participants
Race/Ethnicity, Customized White	134 participants n=5 Participants	133 participants n=7 Participants	129 participants n=5 Participants	130 participants n=4 Participants	526 participants n=21 Participants
Race/Ethnicity, Customized Black or African American	29 participants n=5 Participants	36 participants n=7 Participants	39 participants n=5 Participants	41 participants n=4 Participants	145 participants n=21 Participants
Race/Ethnicity, Customized Asian	8 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants	3 participants n=4 Participants	19 participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska native	1 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	1 participants n=4 Participants	4 participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants	6 participants n=7 Participants	4 participants n=5 Participants	4 participants n=4 Participants	17 participants n=21 Participants
Race/Ethnicity, Customized Hispanic or Latino	20 participants n=5 Participants	22 participants n=7 Participants	28 participants n=5 Participants	22 participants n=4 Participants	92 participants n=21 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	156 participants n=5 Participants	155 participants n=7 Participants	151 participants n=5 Participants	158 participants n=4 Participants	620 participants n=21 Participants
Region of Enrollment United States	176 participants n=5 Participants	178 participants n=7 Participants	179 participants n=5 Participants	180 participants n=4 Participants	713 participants n=21 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 8

Population: 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).

Outcome measures

Outcome measures
Measure	Placebo n=175 Participants Dose matching placebo capsules, oral administration, once daily dosing. Placebo : Matching placebo capsules, oral administration, once daily for 8 weeks.	Levomilnacipran ER 40 mg n=176 Participants 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.	Levomilnacipran ER 80 mg n=177 Participants 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.	Levomilnacipran ER 120 mg n=176 Participants 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.
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score	-11.6 Units on a scale Standard Error 0.97	-14.8 Units on a scale Standard Error 0.99	-15.6 Units on a scale Standard Error 1.00	-16.5 Units on a scale Standard Error 1.02

SECONDARY outcome

Timeframe: From Baseline to Week 8

The Sheehan Disability Scale (SDS) is a 3-item clinician-rated questionnaire used to evaluate functional 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 for all measured symptoms)

Outcome measures

Outcome measures
Measure	Placebo n=175 Participants Dose matching placebo capsules, oral administration, once daily dosing. Placebo : Matching placebo capsules, oral administration, once daily for 8 weeks.	Levomilnacipran ER 40 mg n=176 Participants 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.	Levomilnacipran ER 80 mg n=177 Participants 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.	Levomilnacipran ER 120 mg n=176 Participants 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.
Change in Sheehan Disability Scale (SDS) Total Score	-7.2 units on a scale Standard Error 0.74	-8.6 units on a scale Standard Error 0.75	-9.7 units on a scale Standard Error 0.77	-9.7 units on a scale Standard Error 0.78

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 66 other events

Deaths: 0 deaths

Levomilnacipran ER 40 mg

Serious events: 3 serious events

Other events: 110 other events

Deaths: 0 deaths

Levomilnacipran ER 80 mg

Serious events: 2 serious events

Other events: 122 other events

Deaths: 0 deaths

Levomilnacipran ER 120 mg

Serious events: 1 serious events

Other events: 112 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=176 participants at risk Dose matching placebo capsules, oral administration, once daily dosing for 8 weeks.	Levomilnacipran ER 40 mg n=178 participants at risk 40 mg per day Levomilnacipran ER, low dose, oral administration, once daily for 8 weeks.	Levomilnacipran ER 80 mg n=179 participants at risk 80 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks.	Levomilnacipran ER 120 mg n=180 participants at risk 120 mg per day Levomilnacipran ER capsules, oral administration, once daily for 8 weeks.
Psychiatric disorders Aggression	0.00% 0/176 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.	0.56% 1/178 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/179 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/180 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.
General disorders Chest Pain	0.00% 0/176 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.	0.56% 1/178 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/179 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/180 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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 Cytomegalovirus mononucleosis	0.00% 0/176 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/178 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.	0.56% 1/179 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/180 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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 Deep vein thrombosis	0.00% 0/176 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.	0.56% 1/178 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/179 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/180 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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 Pneumonia	0.57% 1/176 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/178 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/179 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/180 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/176 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.	0.56% 1/178 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/179 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/180 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.
Pregnancy, puerperium and perinatal conditions Premature baby	0.00% 0/108 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/122 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/111 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.	0.94% 1/106 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.
Pregnancy, puerperium and perinatal conditions Small for dates baby	0.00% 0/108 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/122 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/111 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.	0.94% 1/106 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.
Pregnancy, puerperium and perinatal conditions Pre-eclampsia	0.00% 0/108 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/122 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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.	0.90% 1/111 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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% 0/106 • Adverse event data was collected over a 20 month period from September 2009 to June 2011 at 38 study sites. 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

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