A Multicenter, Relapse Prevention Study With Levomilnacip... | NCT02288325

Status Module

Oversight Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Open-Label FETZIMA®	Experimental	FETZIMA® (levomilnacipran extended release [ER]) taken orally during flexible dose titration up to 40, 80 or 120 mg once daily in 8-week run-in period followed by fixed dose of 40, 80 or 120 mg once daily in 12-week stabilization period.	Drug: Levomilnacipran ER
Double-Blind Placebo	Placebo Comparator	Dose-matched placebo taken orally once daily for 26 weeks during double-blind treatment period.	Drug: Placebo
Double-Blind FETZIMA®	Experimental	FETZIMA® (levomilnacipran ER) taken orally at fixed dose of 40, 80 or 120 mg once daily for 26 weeks during double-blind treatment period.	Drug: Levomilnacipran ER

Name	Type	Description	Arm Group Labels	Other Names
Levomilnacipran ER	Drug	Levomilnacipran ER taken orally at 40, 80 or 120 mg once daily.	Double-Blind FETZIMA® Open-Label FETZIMA®

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Time to First Relapse During the Double-Blind Treatment Period (DBTP)	Time to relapse for the median was measured in days from randomization date at the start of the DBTP to relapse date during DBTP. Relapse was defined as meeting any 1 or more of the following criteria: 1) Insufficient therapeutic response at any one visit, including a >/= 2 increase in Clinical Global Impressions-Severity (CGI-S) score (range 1 to 7) compared with that obtained at randomization, or risk of suicide as determined by the investigator, or need for hospitalization due to worsening of depression as determined by the investigator, or need for alternative treatment of depressive symptoms as determined by the Investigator; 2) Montgomery-Asberg Depression Rating Scale (MADRS) total score >/= 18 (range 0 to 60) at 2 consecutive visits (second visit within 7 to 14 days after the first visit at which the MADRS total score was ≥ 18). Participant was considered censored at the last visit during DBTP if participant did not meet the relapse criteria during DBTP.	From the randomization date (Week 20) to the relapse date during the 26-week DBTP (up to Week 46)

Eligibility Module

Name	Affiliation	Role
Raffaele Migliore	Forest Research Institute, Inc., an affiliate of Allergan, plc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Forest Investigative Site 053		Birmingham	Alabama	35294	United States
Forest Investigative Site 050

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Open-Label FETZIMA®	FETZIMA® (levomilnacipran extended release [ER]) taken orally during flexible dose titration up to 40, 80 or 120 mg once daily in 8-week run-in period followed by fixed dose of 40, 80 or 120 mg once daily in 12-week stabilization period.
FG001	Double-Blind Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Time to First Relapse During the Double-Blind Treatment Period (DBTP)

Time to relapse for the median was measured in days from randomization date at the start of the DBTP to relapse date during DBTP. Relapse was defined as meeting any 1 or more of the following criteria: 1) Insufficient therapeutic response at any one visit, including a >/= 2 increase in Clinical Global Impressions-Severity (CGI-S) score (range 1 to 7) compared with that obtained at randomization, or risk of suicide as determined by the investigator, or need for hospitalization due to worsening of depression as determined by the investigator, or need for alternative treatment of depressive symptoms as determined by the Investigator; 2) Montgomery-Asberg Depression Rating Scale (MADRS) total score >/= 18 (range 0 to 60) at 2 consecutive visits (second visit within 7 to 14 days after the first visit at which the MADRS total score was ≥ 18). Participant was considered censored at the last visit during DBTP if participant did not meet the relapse criteria during DBTP.

Double-blind Intent-to-Treat (ITT) population comprised of all participants in the Double-blind Safety Population who had at least 1 post-randomization assessment of MADRS or those participants who met relapse criteria during the DBTP of the study.

Posted

Median

95% Confidence Interval

days

From the randomization date (Week 20) to the relapse date during the 26-week DBTP (up to Week 46)

ID	Title	Description
OG000	Double-Blind Placebo	Dose-matched placebo taken orally once daily for 26 weeks during double-blind treatment period.
OG001	Double-Blind FETZIMA®	FETZIMA® (levomilnacipran ER) taken orally at fixed dose of 40, 80 or 120 mg once daily for 26 weeks during double-blind treatment period.

Units	Counts
Participants	OG000159 OG001165

Title

Denominators

Categories

Title	Measurements
	OG000NA(NA to NA)Not available due to insufficient number of events. OG001NA(NA to NA)Not available due to insufficient number of events.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.0212		Hazard Ratio (HR)	0.56			2-Sided	95	0.33	0.92					Superiority

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Open-Label FETZIMA®	FETZIMA® (levomilnacipran extended release [ER]) taken orally during flexible dose titration up to 40, 80 or 120 mg once daily in 8-week run-in period followed by fixed dose of 40, 80 or 120 mg once daily in 12-week stabilization period.	644	9	644	430	644
EG001	Double-Blind Placebo	Dose-matched placebo taken orally once daily for 26 weeks during double-blind treatment period.	159	1	159	29	159
EG002	Double-Blind FETZIMA®	FETZIMA® (levomilnacipran ER) taken orally at fixed dose of 40, 80 or 120 mg once daily for 26 weeks during double-blind treatment period.	165	2	165	41	165

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Panic attack	Psychiatric disorders	MedDRA version: 19.0	Systematic Assessment	EG0001 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk
Oesophageal squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version: 19.0	Systematic Assessment	EG0001 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk
Migraine	Nervous system disorders	MedDRA version: 19.0	Systematic Assessment	EG0001 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk
Mania	Psychiatric disorders	MedDRA version: 19.0	Systematic Assessment	EG0001 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk
Influenza	Infections and infestations	MedDRA version: 19.0	Systematic Assessment	EG0001 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version: 19.0	Systematic Assessment	EG0001 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA version: 19.0	Systematic Assessment	EG0001 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA version: 19.0	Systematic Assessment	EG0001 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA version: 19.0	Systematic Assessment	EG0001 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk
Agitation	Psychiatric disorders	MedDRA version: 19.0	Systematic Assessment	EG0001 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA version: 19.0	Systematic Assessment	EG0000 affected644 at risk EG0010 affected159 at risk EG0021 affected165 at risk
Escherichia pyelonephritis	Infections and infestations	MedDRA version: 19.0	Systematic Assessment	EG0000 affected644 at risk EG0010 affected159 at risk EG0021 affected165 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA version: 19.0	Systematic Assessment	EG0000 affected644 at risk EG0011 affected159 at risk EG0020 affected165 at risk
Intraocular pressure increased	Investigations	MedDRA version: 19.0	Systematic Assessment	EG0000 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk
Pelvic inflammatory disease	Infections and infestations	MedDRA version: 19.0	Systematic Assessment	EG0000 affected644 at risk EG0010 affected159 at risk EG0020 affected165 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA version: 19.0	Systematic Assessment	EG000174 affected644 at risk EG0015 affected159 at risk EG00213 affected165 at risk
Constipation	Gastrointestinal disorders	MedDRA version: 19.0	Systematic Assessment	EG00069 affected644 at risk EG0013 affected159 at risk EG0023 affected165 at risk
Dry mouth	Gastrointestinal disorders	MedDRA version: 19.0	Systematic Assessment	EG00037 affected644 at risk EG0012 affected159 at risk EG0020 affected165 at risk
Headache	Nervous system disorders	MedDRA version: 19.0	Systematic Assessment	EG000103 affected644 at risk EG00112 affected159 at risk EG00217 affected165 at risk
Dizziness	Nervous system disorders	MedDRA version: 19.0	Systematic Assessment	EG00050 affected644 at risk EG0014 affected159 at risk EG0021 affected165 at risk
Heart rate increased	Investigations	MedDRA version: 19.0	Systematic Assessment	EG00071 affected644 at risk EG0014 affected159 at risk EG0024 affected165 at risk
Blood pressure increased	Investigations	MedDRA version: 19.0	Systematic Assessment	EG00036 affected644 at risk EG0013 affected159 at risk EG0025 affected165 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA version: 19.0	Systematic Assessment	EG00057 affected644 at risk EG0012 affected159 at risk EG0021 affected165 at risk
Tachycardia	Cardiac disorders	MedDRA version: 19.0	Systematic Assessment	EG00050 affected644 at risk EG0013 affected159 at risk EG0026 affected165 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA version: 19.0	Systematic Assessment	EG00046 affected644 at risk EG00110 affected159 at risk EG00216 affected165 at risk
Insomnia	Psychiatric disorders	MedDRA version: 19.0	Systematic Assessment	EG00034 affected644 at risk EG0012 affected159 at risk EG0025 affected165 at risk
Nasopharyngitis	Infections and infestations	MedDRA version: 19.0	Systematic Assessment	EG00025 affected644 at risk EG0017 affected159 at risk EG00211 affected165 at risk

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders

ID	Term
D000078764	Milnacipran
D003521	Cyclopropanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals