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

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01085812
• Collaborator: (none)
• Enrollment: 734
• Locations: 35
• Arms: 2
• Duration (Months): 19
• Patients Per Site: 21
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of Levomilnacipran ER relative to placebo in the prevention of depression relapse in patients with major depressive disorder (MDD).

Condition or Disease	Intervention/Treatment	Phase
Depression; Major Depressive Disorder	Drug: Levomilnacipran ER; Drug: Placebo	Phase 3

Detailed Description

Patients who demonstrate improvement in depressive symptoms at the end of the initial 12-week open-label treatment period with Levomilnacipran ER are randomized to continue Levomilnacipran ER or switch to placebo under double-blind conditions for up to 24 weeks of additional treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 734 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-Controlled, Relapse-Prevention Study With F2695 SR in Patients With Major Depressive Disorder
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2 40, 80 or 120 mg/day Levomilnacipran ER capsules, oral administration, once daily dosing.	Drug: Levomilnacipran ER; Drug: Levomilnacipran ER (40, 80 or 120 mg/day) Study drug is to be given orally, in capsule form, once daily.
Placebo Comparator: 1 Matching placebo capsules, oral administration, once daily dosing.	Drug: Placebo; Matching placebo to be given orally, in capsule form, once daily.

Outcome Measures

Primary Outcome Measures

1. Time to Relapse (Days) [24 Weeks]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women, 18-65 years old

• Currently meet the DSM-IV-TR criteria for Major Depressive Disorder

• The patient's current depressive episode must be at least 4 weeks in duration

Exclusion Criteria:

• Women who are pregnant, women who will be breastfeeding during the study, and women with childbearing potential who are not practicing a reliable method of birth control

• Patients with a history of meeting DSM-IV-TR criteria for:

• any manic or hypomanic episode

• schizophrenia or any other psychotic disorder

• obsessive-compulsive disorder

• Patients who are considered a suicide risk

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site #023	Beverly Hills	California	United States	90210
2	Forest Investigative Site #017	Encino	California	United States	31316
3	Forest Investigative Site #021	Garden Grove	California	United States	92845
4	Forest Investigative Site #025	Newport Beach	California	United States	92660
5	Forest Investigative Site #030	Orange	California	United States	92868
6	Forest Investigative Site #002	San Diego	California	United States	92108
7	Forest Investigative Site #003	Sherman Oaks	California	United States	91403
8	Forest Research Institute #001	Bonita Springs	Florida	United States	34134
9	Forest Investigative Site #015	Fort Myers	Florida	United States	33912
10	Forest Investigative Site #029	Maitland	Florida	United States	32751
11	Forest Investigative Site #005	North Miami	Florida	United States	33161
12	Forest Investigative Site #016	Orlando	Florida	United States	32806
13	Forest Investigative Site #004	South Miami	Florida	United States	33143
14	Forest Investigative Site #014	Atlanta	Georgia	United States	30328
15	Forest Investigative Site #022	Chicago	Illinois	United States	60634
16	Forest Investigative Site #006	Chicago	Illinois	United States	60640
17	Forest Investigative Site #009	Prairie Village	Kansas	United States	66206
18	Forest Investigative Site #013	Baltimore	Maryland	United States	21208
19	Forest Investigative Site #010	Boston	Massachusetts	United States	02135
20	Forest Investigative Site #012	Saint Louis	Missouri	United States	63139
21	Forest Investigative Site #011	Staten Island	New York	United States	10312
22	Forest Investigative Site #026	Portland	Oregon	United States	97210
23	Forest Investigative Site #008	Bridgeville	Pennsylvania	United States	15017
24	Forest Investigative Site #028	Norristown	Pennsylvania	United States	19401
25	Forest Investigative Site #020	Philadelphia	Pennsylvania	United States	19139
26	Forest Investigative Site #024	Memphis	Tennessee	United States	38119
27	Forest Investigative Site #007	Dallas	Texas	United States	75231
28	Forest Investigative Site #019	San Antonio	Texas	United States	78229
29	Forest Investigative Site #018	Bellevue	Washington	United States	98007
30	Forest Investigative Site #027	Seattle	Washington	United States	98104
31	Forest Investigative Site #050	Kelowna	British Columbia	Canada	V1Y 1Z9
32	Forest Investigative Site #051	Vancouver	British Columbia	Canada	V6Z 2L4
33	Forest Investigative Site #052	Sydney	Nova Scotia	Canada	B1S 2E8
34	Forest Investigative Site #055	Chatham	Ontario	Canada	N7M 1B7
35	Forest Investigative Site #053	Ottawa	Ontario	Canada	K1G 4G3

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Study Director: Giovanna Forero, MA, Forest Laboratories

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT01085812
• Other Study ID Numbers: LVM-MD-05
• First Posted: Mar 12, 2010
• Last Update Posted: Jan 13, 2020
• Last Verified: Dec 1, 2019

• Additional relevant MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Milnacipran; Levomilnacipran

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	Patients began with a 12-week open-label treatment period, followed by a 24-week double-blind treatment period.

Arm/Group Title	Placebo	Levomilnacipran ER
Arm/Group Description	Matching placebo capsules, oral administration, once daily dosing.	40, 80 or 120 mg/day Levomilnacipran ER capsules, oral administration, once daily dosing.
Period Title: Open-Label Period
STARTED	0	734
COMPLETED	0	494
NOT COMPLETED	0	240
Period Title: Open-Label Period
STARTED	113	235
COMPLETED	92	177
NOT COMPLETED	21	58
Period Title: Open-Label Period
STARTED	112	230
COMPLETED	92	174
NOT COMPLETED	20	56

Baseline Characteristics

Arm/Group Title	Open Label Levomilnacipran ER
Arm/Group Description	40, 80 or 120 mg Levomilnacipran ER capsules, oral administration, once daily dosing.
Overall Participants	734
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.2 (12.3)
Age, Customized (Count of Participants)
18 years to 19 years	8 1.1%
20 years to 29 years	151 20.6%
30 years to 39 years	127 17.3%
40 years to 49 years	208 28.3%
50 years to 59 years	186 25.3%
60 years to 65 years	54 7.4%
Sex: Female, Male (Count of Participants)
Female	425 57.9%
Male	309 42.1%
Region of Enrollment (Count of Participants)
United States	683 93.1%
Canada	51 6.9%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	83.41 (18.43)
Body Mass Index (BMI) (Kilograms Per Meter Squared) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms Per Meter Squared]	28.88 (5.42)

Outcome Measures

1. Primary Outcome

Title	Time to Relapse (Days)
Description	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
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Levomilnacipran ER
Arm/Group Description	Matching placebo capsules, oral administration, once daily dosing.	40, 80 or 120 mg Levomilnacipran ER capsules, oral administration, once daily dosing.
Measure Participants	112	230
Mean (Standard Deviation) [Days]	NA (NA)	NA (NA)

Adverse Events

Time Frame	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.
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 24 week double-blind treatment period.
Arm/Group Title	Open Label Levomilnacipran ER		Placebo - Double Blind Treatment		Levomilnacipran ER - Double Blind Treatment
Arm/Group Description	40, 80 or 120 mg Levomilnacipran ER capsules, oral administration, once daily dosing.		Matching placebo capsules, oral administration, once daily dosing.		40, 80 or 120 mg Levomilnacipran ER capsules, oral administration, once daily dosing.
All Cause Mortality
	Open Label Levomilnacipran ER		Placebo - Double Blind Treatment		Levomilnacipran ER - Double Blind Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/734 (0%)		0/112 (0%)		0/233 (0%)
Serious Adverse Events
	Open Label Levomilnacipran ER		Placebo - Double Blind Treatment		Levomilnacipran ER - Double Blind Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/734 (1%)		4/112 (3.6%)		2/233 (0.9%)
Gastrointestinal disorders
Intestinal ischaemia	0/734 (0%)		0/112 (0%)		1/233 (0.4%)
Pancreatitis acute	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
General disorders
Chest pain	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Non-cardiac chest pain	0/734 (0%)		0/112 (0%)		1/233 (0.4%)
Hepatobiliary disorders
Cholelithiasis	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Immune system disorders
Drug hypersensitivity	0/734 (0%)		1/112 (0.9%)		0/233 (0%)
Infections and infestations
Cellulitis	0/734 (0%)		1/112 (0.9%)		0/233 (0%)
Pneumonia	0/734 (0%)		1/112 (0.9%)		0/233 (0%)
Staphylococcal infection	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Injury, poisoning and procedural complications
Ankle fracture	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Fall	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Investigations
Blood creatine phosphokinase MB increased	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Blood pressure increased	0/734 (0%)		1/112 (0.9%)		0/233 (0%)
Troponin I increased	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Psychiatric disorders
Drug abuse	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Intentional self-injury	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Suicidal behaviour	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Suicide attempt	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Vascular disorders
Deep vein thrombosis	0/734 (0%)		1/112 (0.9%)		0/233 (0%)
Hypertension	1/734 (0.1%)		0/112 (0%)		0/233 (0%)
Other (Not Including Serious) Adverse Events
	Open Label Levomilnacipran ER		Placebo - Double Blind Treatment		Levomilnacipran ER - Double Blind Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	448/734 (61%)		31/112 (27.7%)		68/233 (29.2%)
Gastrointestinal disorders
Nausea	160/734 (21.8%)		5/112 (4.5%)		13/233 (5.6%)
Constipation	82/734 (11.2%)		5/112 (4.5%)		2/233 (0.9%)
Dry mouth	78/734 (10.6%)		1/112 (0.9%)		3/233 (1.3%)
Infections and infestations
Upper respiratory tract infection	51/734 (6.9%)		10/112 (8.9%)		17/233 (7.3%)
Nasopharyngitis	25/734 (3.4%)		9/112 (8%)		20/233 (8.6%)
Investigations
Heart rate increased	54/734 (7.4%)		1/112 (0.9%)		3/233 (1.3%)
Nervous system disorders
Headache	141/734 (19.2%)		11/112 (9.8%)		31/233 (13.3%)
Dizziness	78/734 (10.6%)		5/112 (4.5%)		4/233 (1.7%)
Psychiatric disorders
Insomnia	63/734 (8.6%)		5/112 (4.5%)		5/233 (2.1%)
Reproductive system and breast disorders
Erectile dysfunction	27/309 (8.7%)		1/51 (2%)		1/94 (1.1%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	80/734 (10.9%)		1/112 (0.9%)		4/233 (1.7%)

Limitations/Caveats

This was a failed study. The lower than expected rate of relapse in the placebo group compromised the projected power to demonstrate a difference between groups.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.