Trial Outcomes & Findings for A Multicenter, Relapse Prevention Study With Levomilnacipran Extended Release (ER) in Participants With Major Depressive Disorder (NCT NCT02288325)
NCT ID: NCT02288325
Last Updated: 2018-10-29
Results Overview
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.
COMPLETED
PHASE4
644 participants
From the randomization date (Week 20) to the relapse date during the 26-week DBTP (up to Week 46)
2018-10-29
Participant Flow
Participant milestones
| Measure |
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.
|
Double-Blind Placebo
Dose-matched placebo taken orally once daily for 26 weeks during double-blind treatment period.
|
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.
|
|---|---|---|---|
|
Run-in Period
STARTED
|
644
|
0
|
0
|
|
Run-in Period
COMPLETED
|
499
|
0
|
0
|
|
Run-in Period
NOT COMPLETED
|
145
|
0
|
0
|
|
Stabilization Period
STARTED
|
429
|
0
|
0
|
|
Stabilization Period
COMPLETED
|
331
|
0
|
0
|
|
Stabilization Period
NOT COMPLETED
|
98
|
0
|
0
|
|
Double-blind Treatment Period
STARTED
|
0
|
159
|
165
|
|
Double-blind Treatment Period
COMPLETED
|
0
|
135
|
139
|
|
Double-blind Treatment Period
NOT COMPLETED
|
0
|
24
|
26
|
Reasons for withdrawal
| Measure |
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.
|
Double-Blind Placebo
Dose-matched placebo taken orally once daily for 26 weeks during double-blind treatment period.
|
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.
|
|---|---|---|---|
|
Run-in Period
Adverse Event
|
48
|
0
|
0
|
|
Run-in Period
Lack of Efficacy
|
16
|
0
|
0
|
|
Run-in Period
Withdrawal of Consent
|
28
|
0
|
0
|
|
Run-in Period
Lost to Follow-up
|
25
|
0
|
0
|
|
Run-in Period
Protocol Violation
|
17
|
0
|
0
|
|
Run-in Period
Non-Compliance With Study Drug
|
3
|
0
|
0
|
|
Run-in Period
Reason not Specified
|
8
|
0
|
0
|
|
Stabilization Period
Adverse Event
|
13
|
0
|
0
|
|
Stabilization Period
Lack of Efficacy
|
22
|
0
|
0
|
|
Stabilization Period
Withdrawal of Consent
|
23
|
0
|
0
|
|
Stabilization Period
Lost to Follow-up
|
12
|
0
|
0
|
|
Stabilization Period
Protocol Violation
|
8
|
0
|
0
|
|
Stabilization Period
Non-Compliance With Study Drug
|
5
|
0
|
0
|
|
Stabilization Period
Reason not Specified
|
15
|
0
|
0
|
|
Double-blind Treatment Period
Adverse Event
|
0
|
2
|
5
|
|
Double-blind Treatment Period
Withdrawal of Consent
|
0
|
8
|
8
|
|
Double-blind Treatment Period
Lost to Follow-up
|
0
|
4
|
5
|
|
Double-blind Treatment Period
Protocol Violation
|
0
|
1
|
2
|
|
Double-blind Treatment Period
Non-Compliance With Study Drug
|
0
|
1
|
4
|
|
Double-blind Treatment Period
Multiple Reasons
|
0
|
8
|
2
|
Baseline Characteristics
A Multicenter, Relapse Prevention Study With Levomilnacipran Extended Release (ER) in Participants With Major Depressive Disorder
Baseline characteristics by cohort
| Measure |
Open-Label FETZIMA®
n=644 Participants
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.
|
|---|---|
|
Age, Continuous
|
43.1 years
STANDARD_DEVIATION 13.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
404 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
240 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From the randomization date (Week 20) to the relapse date during the 26-week DBTP (up to Week 46)Population: 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.
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.
Outcome measures
| Measure |
Double-Blind Placebo
n=159 Participants
Dose-matched placebo taken orally once daily for 26 weeks during double-blind treatment period.
|
Double-Blind FETZIMA®
n=165 Participants
FETZIMA® (levomilnacipran ER) taken orally at fixed dose of 40, 80 or 120 mg once daily for 26 weeks during double-blind treatment period.
|
|---|---|---|
|
Time to First Relapse During the Double-Blind Treatment Period (DBTP)
|
NA days
Not available due to insufficient number of events.
|
NA days
Not available due to insufficient number of events.
|
Adverse Events
Open-Label FETZIMA®
Double-Blind Placebo
Double-Blind FETZIMA®
Serious adverse events
| Measure |
Open-Label FETZIMA®
n=644 participants at risk
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.
|
Double-Blind Placebo
n=159 participants at risk
Dose-matched placebo taken orally once daily for 26 weeks during double-blind treatment period.
|
Double-Blind FETZIMA®
n=165 participants at risk
FETZIMA® (levomilnacipran ER) taken orally at fixed dose of 40, 80 or 120 mg once daily for 26 weeks during double-blind treatment period.
|
|---|---|---|---|
|
Psychiatric disorders
Panic attack
|
0.16%
1/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal squamous cell carcinoma
|
0.16%
1/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Nervous system disorders
Migraine
|
0.16%
1/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Psychiatric disorders
Mania
|
0.16%
1/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Infections and infestations
Influenza
|
0.16%
1/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.16%
1/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.16%
1/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.16%
1/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Hepatobiliary disorders
Bile duct stone
|
0.16%
1/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Psychiatric disorders
Agitation
|
0.16%
1/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.61%
1/165 • Up to 48 weeks
|
|
Infections and infestations
Escherichia pyelonephritis
|
0.00%
0/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.61%
1/165 • Up to 48 weeks
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/644 • Up to 48 weeks
|
0.63%
1/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Investigations
Intraocular pressure increased
|
0.00%
0/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Infections and infestations
Pelvic inflammatory disease
|
0.00%
0/644 • Up to 48 weeks
|
0.00%
0/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
Other adverse events
| Measure |
Open-Label FETZIMA®
n=644 participants at risk
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.
|
Double-Blind Placebo
n=159 participants at risk
Dose-matched placebo taken orally once daily for 26 weeks during double-blind treatment period.
|
Double-Blind FETZIMA®
n=165 participants at risk
FETZIMA® (levomilnacipran ER) taken orally at fixed dose of 40, 80 or 120 mg once daily for 26 weeks during double-blind treatment period.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
27.0%
174/644 • Up to 48 weeks
|
3.1%
5/159 • Up to 48 weeks
|
7.9%
13/165 • Up to 48 weeks
|
|
Gastrointestinal disorders
Constipation
|
10.7%
69/644 • Up to 48 weeks
|
1.9%
3/159 • Up to 48 weeks
|
1.8%
3/165 • Up to 48 weeks
|
|
Gastrointestinal disorders
Dry mouth
|
5.7%
37/644 • Up to 48 weeks
|
1.3%
2/159 • Up to 48 weeks
|
0.00%
0/165 • Up to 48 weeks
|
|
Nervous system disorders
Headache
|
16.0%
103/644 • Up to 48 weeks
|
7.5%
12/159 • Up to 48 weeks
|
10.3%
17/165 • Up to 48 weeks
|
|
Nervous system disorders
Dizziness
|
7.8%
50/644 • Up to 48 weeks
|
2.5%
4/159 • Up to 48 weeks
|
0.61%
1/165 • Up to 48 weeks
|
|
Investigations
Heart rate increased
|
11.0%
71/644 • Up to 48 weeks
|
2.5%
4/159 • Up to 48 weeks
|
2.4%
4/165 • Up to 48 weeks
|
|
Investigations
Blood pressure increased
|
5.6%
36/644 • Up to 48 weeks
|
1.9%
3/159 • Up to 48 weeks
|
3.0%
5/165 • Up to 48 weeks
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
8.9%
57/644 • Up to 48 weeks
|
1.3%
2/159 • Up to 48 weeks
|
0.61%
1/165 • Up to 48 weeks
|
|
Cardiac disorders
Tachycardia
|
7.8%
50/644 • Up to 48 weeks
|
1.9%
3/159 • Up to 48 weeks
|
3.6%
6/165 • Up to 48 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
7.1%
46/644 • Up to 48 weeks
|
6.3%
10/159 • Up to 48 weeks
|
9.7%
16/165 • Up to 48 weeks
|
|
Psychiatric disorders
Insomnia
|
5.3%
34/644 • Up to 48 weeks
|
1.3%
2/159 • Up to 48 weeks
|
3.0%
5/165 • Up to 48 weeks
|
|
Infections and infestations
Nasopharyngitis
|
3.9%
25/644 • Up to 48 weeks
|
4.4%
7/159 • Up to 48 weeks
|
6.7%
11/165 • Up to 48 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER