Trial Outcomes & Findings for Relapse-Prevention Study With Levomilnacipran ER (F2695 SR) in Patients With Major Depressive Disorder (NCT NCT01085812)

Last Updated: 2020-01-13

Results Overview

Number of days until patients meet relapse criteria. Relapse was defined as 1 or more of the following: 1. MADRS total score of at least 22 at 2 consecutive visits 2. Increase of 2 or more points in CGI-I score compared with the CGI-I score at Visit 9 at 2 consecutive visits 3. Premature discontinuation due to insufficient therapeutic response 4. MADRS item 10 score of at least 4

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

734 participants

Primary outcome timeframe

24 Weeks

Results posted on

2020-01-13

Participant Flow

Patient were recruited over a 10-month period from March of 2010 to January of 2011 at 36 studies sites, 30 in the United States and 6 in Canada.

Patients began with a 12-week open-label treatment period, followed by a 24-week double-blind treatment period.

Participant milestones

Participant milestones
Measure	Placebo Matching placebo capsules, oral administration, once daily dosing.	Levomilnacipran ER 40, 80 or 120 mg/day Levomilnacipran ER capsules, oral administration, once daily dosing.
Open-Label Period STARTED	0	734
Open-Label Period COMPLETED	0	494
Open-Label Period NOT COMPLETED	0	240
Double-Blind Period STARTED	113	235
Double-Blind Period COMPLETED	92	177
Double-Blind Period NOT COMPLETED	21	58
Double-blind Intent-to-treat Population STARTED	112	230
Double-blind Intent-to-treat Population COMPLETED	92	174
Double-blind Intent-to-treat Population NOT COMPLETED	20	56

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo capsules, oral administration, once daily dosing.	Levomilnacipran ER 40, 80 or 120 mg/day Levomilnacipran ER capsules, oral administration, once daily dosing.
Open-Label Period Adverse Event	0	80
Open-Label Period Lack of Efficacy	0	26
Open-Label Period Protocol Violation	0	39
Open-Label Period Withdrawal by Subject	0	53
Open-Label Period Lost to Follow-up	0	42
Double-Blind Period Adverse Event	3	8
Double-Blind Period Protocol Violation	2	7
Double-Blind Period Withdrawal by Subject	11	24
Double-Blind Period Lost to Follow-up	5	17
Double-Blind Period Other Reasons	0	2
Double-blind Intent-to-treat Population Adverse Event	3	8
Double-blind Intent-to-treat Population Protocol Violation	2	7
Double-blind Intent-to-treat Population Withdrawal by Subject	11	22
Double-blind Intent-to-treat Population Lost to Follow-up	4	17
Double-blind Intent-to-treat Population Positive serum pregnancy test result	0	2

Baseline Characteristics

Relapse-Prevention Study With Levomilnacipran ER (F2695 SR) in Patients With Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open Label Levomilnacipran ER n=734 Participants 40, 80 or 120 mg Levomilnacipran ER capsules, oral administration, once daily dosing.
Age, Continuous	42.2 years STANDARD_DEVIATION 12.3 • n=5 Participants
Age, Customized 18 years to 19 years	8 Participants n=5 Participants
Age, Customized 20 years to 29 years	151 Participants n=5 Participants
Age, Customized 30 years to 39 years	127 Participants n=5 Participants
Age, Customized 40 years to 49 years	208 Participants n=5 Participants
Age, Customized 50 years to 59 years	186 Participants n=5 Participants
Age, Customized 60 years to 65 years	54 Participants n=5 Participants
Sex: Female, Male Female	425 Participants n=5 Participants
Sex: Female, Male Male	309 Participants n=5 Participants
Region of Enrollment United States	683 Participants n=5 Participants
Region of Enrollment Canada	51 Participants n=5 Participants
Weight	83.41 kg STANDARD_DEVIATION 18.43 • n=5 Participants
Body Mass Index (BMI)	28.88 Kilograms Per Meter Squared STANDARD_DEVIATION 5.42 • n=5 Participants

PRIMARY outcome

Timeframe: 24 Weeks

Population: The double blind Intent-to-treat population consists of 342 randomized participants who received study drug and were evaluated for the Primary Outcome Measure

Outcome measures

Outcome measures
Measure	Placebo n=112 Participants Matching placebo capsules, oral administration, once daily dosing.	Levomilnacipran ER n=230 Participants 40, 80 or 120 mg Levomilnacipran ER capsules, oral administration, once daily dosing.
Time to Relapse (Days)	NA Days Standard Deviation NA Relapse did not occur within the 24-week time frame of the study	NA Days Standard Deviation NA Relapse did not occur within the 24-week time frame of the study

Adverse Events

Open Label Levomilnacipran ER

Serious events: 7 serious events

Other events: 448 other events

Deaths: 0 deaths

Placebo - Double Blind Treatment

Serious events: 4 serious events

Other events: 31 other events

Deaths: 0 deaths

Levomilnacipran ER - Double Blind Treatment

Serious events: 2 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Open Label Levomilnacipran ER n=734 participants at risk 40, 80 or 120 mg Levomilnacipran ER capsules, oral administration, once daily dosing.	Placebo - Double Blind Treatment n=112 participants at risk Matching placebo capsules, oral administration, once daily dosing.	Levomilnacipran ER - Double Blind Treatment n=233 participants at risk 40, 80 or 120 mg Levomilnacipran ER capsules, oral administration, once daily dosing.
Gastrointestinal disorders Nausea	21.8% 160/734 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	4.5% 5/112 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	5.6% 13/233 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.
Nervous system disorders Headache	19.2% 141/734 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	9.8% 11/112 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	13.3% 31/233 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.
Gastrointestinal disorders Constipation	11.2% 82/734 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	4.5% 5/112 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	0.86% 2/233 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.
Skin and subcutaneous tissue disorders Hyperhidrosis	10.9% 80/734 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	0.89% 1/112 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	1.7% 4/233 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.
Nervous system disorders Dizziness	10.6% 78/734 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	4.5% 5/112 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	1.7% 4/233 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.
Gastrointestinal disorders Dry mouth	10.6% 78/734 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	0.89% 1/112 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	1.3% 3/233 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.
Reproductive system and breast disorders Erectile dysfunction	8.7% 27/309 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	2.0% 1/51 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	1.1% 1/94 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.
Psychiatric disorders Insomnia	8.6% 63/734 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	4.5% 5/112 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	2.1% 5/233 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.
Investigations Heart rate increased	7.4% 54/734 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	0.89% 1/112 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	1.3% 3/233 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.
Infections and infestations Upper respiratory tract infection	6.9% 51/734 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	8.9% 10/112 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	7.3% 17/233 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.
Infections and infestations Nasopharyngitis	3.4% 25/734 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	8.0% 9/112 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 week double-blind treatment period.	8.6% 20/233 • Adverse event data was collection over a 20-month period from March 2010 to November 2011 at 36 study sites in the U.S and Canada. 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 24 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