Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of Levomilnacipran ER in Pediatric Patients (7-17 Years) With Major Depressive Disorder (NCT NCT03569475)
NCT ID: NCT03569475
Last Updated: 2022-03-25
Results Overview
The CDRS-R is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6-17 years. It contains 17 ordinally-scaled items that evaluate the presence and severity of symptoms commonly associated with childhood depression and is scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. The CDRS-R total score ranges from 17 to 113; higher score indicates more severe depression. A negative change from Baseline indicates improvement. Mixed Model for Repeated Measures (MMRM) was used for analysis.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
501 participants
Primary outcome timeframe
Baseline (Week 0) to Week 8
Results posted on
2022-03-25
Participant Flow
Participant milestones
| Measure |
Placebo
Matching placebo capsules once daily through 8 weeks in the Double-blind Treatment Period and Days 1 through 7 in the Down-taper Period.
|
Levomilnacipran ER 40-80 mg/Day
Levomilnacipran extended release (ER) capsules, orally, 10 milligram per day (mg/day) on Days 1 to 3, 20 mg/day on Days 4 to 7, and 40 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period followed by levomilnacipran ER 40 mg/day on Days 1 and 2, and then 20 mg/day from Day 3 through Day 7 in the Down-taper Period. Based on therapeutic response and tolerability, an additional dose increase to 80 mg/day was permitted at Week 3 of the Double-blind Treatment Period.
|
Fluoxetine 20 mg/Day
Fluoxetine capsule, orally, 10 mg/day at Week 1, and 20 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period followed by fluoxetine 10 mg/day from Day 1 through Day 7 of the Down-taper Period.
|
|---|---|---|---|
|
Double-blind Treatment Period (8 Weeks)
STARTED
|
164
|
169
|
168
|
|
Double-blind Treatment Period (8 Weeks)
Safety Population
|
160
|
166
|
166
|
|
Double-blind Treatment Period (8 Weeks)
COMPLETED
|
146
|
146
|
144
|
|
Double-blind Treatment Period (8 Weeks)
NOT COMPLETED
|
18
|
23
|
24
|
|
Double-blind Down-taper Period (1 Week)
STARTED
|
140
|
141
|
140
|
|
Double-blind Down-taper Period (1 Week)
COMPLETED
|
140
|
139
|
138
|
|
Double-blind Down-taper Period (1 Week)
NOT COMPLETED
|
0
|
2
|
2
|
Reasons for withdrawal
| Measure |
Placebo
Matching placebo capsules once daily through 8 weeks in the Double-blind Treatment Period and Days 1 through 7 in the Down-taper Period.
|
Levomilnacipran ER 40-80 mg/Day
Levomilnacipran extended release (ER) capsules, orally, 10 milligram per day (mg/day) on Days 1 to 3, 20 mg/day on Days 4 to 7, and 40 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period followed by levomilnacipran ER 40 mg/day on Days 1 and 2, and then 20 mg/day from Day 3 through Day 7 in the Down-taper Period. Based on therapeutic response and tolerability, an additional dose increase to 80 mg/day was permitted at Week 3 of the Double-blind Treatment Period.
|
Fluoxetine 20 mg/Day
Fluoxetine capsule, orally, 10 mg/day at Week 1, and 20 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period followed by fluoxetine 10 mg/day from Day 1 through Day 7 of the Down-taper Period.
|
|---|---|---|---|
|
Double-blind Treatment Period (8 Weeks)
Adverse Event
|
1
|
2
|
5
|
|
Double-blind Treatment Period (8 Weeks)
Lack of Efficacy
|
0
|
1
|
0
|
|
Double-blind Treatment Period (8 Weeks)
Withdrawal by Subject
|
7
|
10
|
9
|
|
Double-blind Treatment Period (8 Weeks)
Lost to Follow-up
|
7
|
7
|
6
|
|
Double-blind Treatment Period (8 Weeks)
Protocol Deviation
|
1
|
1
|
1
|
|
Double-blind Treatment Period (8 Weeks)
Non-compliance with Study Drug
|
1
|
1
|
1
|
|
Double-blind Treatment Period (8 Weeks)
Reason not Specified
|
1
|
1
|
2
|
|
Double-blind Down-taper Period (1 Week)
Lost to Follow-up
|
0
|
1
|
1
|
|
Double-blind Down-taper Period (1 Week)
Withdrawal by Subject
|
0
|
1
|
1
|
Baseline Characteristics
Intent-to-Treat (ITT) Population included all participants in the Safety Population who had the Baseline and at least 1 post-baseline assessment of the CDRS-R total score. If a participant received an intervention different from the planned intervention, the participant is counted in the planned group.
Baseline characteristics by cohort
| Measure |
Placebo
n=160 Participants
Matching placebo capsules once daily through 8 weeks in the Double-blind Treatment Period and Days 1 through 7 in the Down-taper Period.
|
Levomilnacipran ER 40-80 mg/Day
n=166 Participants
Levomilnacipran ER capsules, orally, 10 mg/day on Days 1 to 3, 20 mg/day on Days 4 to 7, and 40 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period followed by levomilnacipran ER 40 mg/day on Days 1 and 2, and then 20 mg/day from Day 3 through Day 7 in the Down-taper Period. Based on therapeutic response and tolerability, an additional dose increase to 80 mg/day was permitted at Week 3 of the Double-blind Treatment Period.
|
Fluoxetine 20 mg/Day
n=166 Participants
Fluoxetine capsule, orally, 10 mg/day at Week 1, and 20 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period followed by fluoxetine 10 mg/day from Day 1 through Day 7 of the Down-taper Period.
|
Total
n=492 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
13.6 years
STANDARD_DEVIATION 2.48 • n=160 Participants
|
13.7 years
STANDARD_DEVIATION 2.56 • n=166 Participants
|
13.3 years
STANDARD_DEVIATION 2.66 • n=166 Participants
|
13.5 years
STANDARD_DEVIATION 2.57 • n=492 Participants
|
|
Sex: Female, Male
Female
|
114 Participants
n=160 Participants
|
99 Participants
n=166 Participants
|
105 Participants
n=166 Participants
|
318 Participants
n=492 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=160 Participants
|
67 Participants
n=166 Participants
|
61 Participants
n=166 Participants
|
174 Participants
n=492 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
45 Participants
n=160 Participants
|
40 Participants
n=166 Participants
|
40 Participants
n=166 Participants
|
125 Participants
n=492 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
115 Participants
n=160 Participants
|
126 Participants
n=166 Participants
|
126 Participants
n=166 Participants
|
367 Participants
n=492 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=160 Participants
|
0 Participants
n=166 Participants
|
0 Participants
n=166 Participants
|
0 Participants
n=492 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=160 Participants
|
0 Participants
n=166 Participants
|
1 Participants
n=166 Participants
|
2 Participants
n=492 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=160 Participants
|
4 Participants
n=166 Participants
|
0 Participants
n=166 Participants
|
6 Participants
n=492 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=160 Participants
|
0 Participants
n=166 Participants
|
0 Participants
n=166 Participants
|
0 Participants
n=492 Participants
|
|
Race (NIH/OMB)
Black or African American
|
54 Participants
n=160 Participants
|
61 Participants
n=166 Participants
|
58 Participants
n=166 Participants
|
173 Participants
n=492 Participants
|
|
Race (NIH/OMB)
White
|
102 Participants
n=160 Participants
|
96 Participants
n=166 Participants
|
104 Participants
n=166 Participants
|
302 Participants
n=492 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=160 Participants
|
5 Participants
n=166 Participants
|
3 Participants
n=166 Participants
|
9 Participants
n=492 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=160 Participants
|
0 Participants
n=166 Participants
|
0 Participants
n=166 Participants
|
0 Participants
n=492 Participants
|
|
Children's Depression Rating Scale-Revised (CDRS-R) Total Score
|
60.8 score on a scale
STANDARD_DEVIATION 8.99 • n=159 Participants • Intent-to-Treat (ITT) Population included all participants in the Safety Population who had the Baseline and at least 1 post-baseline assessment of the CDRS-R total score. If a participant received an intervention different from the planned intervention, the participant is counted in the planned group.
|
60.8 score on a scale
STANDARD_DEVIATION 9.17 • n=162 Participants • Intent-to-Treat (ITT) Population included all participants in the Safety Population who had the Baseline and at least 1 post-baseline assessment of the CDRS-R total score. If a participant received an intervention different from the planned intervention, the participant is counted in the planned group.
|
60.9 score on a scale
STANDARD_DEVIATION 9.88 • n=166 Participants • Intent-to-Treat (ITT) Population included all participants in the Safety Population who had the Baseline and at least 1 post-baseline assessment of the CDRS-R total score. If a participant received an intervention different from the planned intervention, the participant is counted in the planned group.
|
60.8 score on a scale
STANDARD_DEVIATION 9.34 • n=487 Participants • Intent-to-Treat (ITT) Population included all participants in the Safety Population who had the Baseline and at least 1 post-baseline assessment of the CDRS-R total score. If a participant received an intervention different from the planned intervention, the participant is counted in the planned group.
|
|
Clinical Global Impression-Severity (CGI-S) Scale
|
4.8 score on a scale
STANDARD_DEVIATION 0.64 • n=159 Participants • ITT Population included all participants in the Safety Population who had the Baseline and at least 1 post-baseline assessment of the CDRS-R total score. If a participant received an intervention different from the planned intervention, the participant is counted in the planned group.
|
4.7 score on a scale
STANDARD_DEVIATION 0.64 • n=162 Participants • ITT Population included all participants in the Safety Population who had the Baseline and at least 1 post-baseline assessment of the CDRS-R total score. If a participant received an intervention different from the planned intervention, the participant is counted in the planned group.
|
4.8 score on a scale
STANDARD_DEVIATION 0.60 • n=166 Participants • ITT Population included all participants in the Safety Population who had the Baseline and at least 1 post-baseline assessment of the CDRS-R total score. If a participant received an intervention different from the planned intervention, the participant is counted in the planned group.
|
4.8 score on a scale
STANDARD_DEVIATION 0.63 • n=487 Participants • ITT Population included all participants in the Safety Population who had the Baseline and at least 1 post-baseline assessment of the CDRS-R total score. If a participant received an intervention different from the planned intervention, the participant is counted in the planned group.
|
PRIMARY outcome
Timeframe: Baseline (Week 0) to Week 8Population: ITT Population included all participants in the Safety Population who had the baseline and at least 1 postbaseline assessment of the CDRS-R total score. Overall number of participants analyzed are the number of participants with data available for analyses.
The CDRS-R is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6-17 years. It contains 17 ordinally-scaled items that evaluate the presence and severity of symptoms commonly associated with childhood depression and is scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. The CDRS-R total score ranges from 17 to 113; higher score indicates more severe depression. A negative change from Baseline indicates improvement. Mixed Model for Repeated Measures (MMRM) was used for analysis.
Outcome measures
| Measure |
Placebo
n=146 Participants
Matching placebo capsules once daily through 8 weeks in the Double-blind Treatment Period and Days 1 through 7 in the Down-taper Period.
|
Levomilnacipran ER 40-80 mg/Day
n=148 Participants
Levomilnacipran ER capsules, orally, 10 mg/day on Days 1 to 3, 20 mg/day on Days 4 to 7, and 40 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period followed by levomilnacipran ER 40 mg/day on Days 1 and 2, and then 20 mg/day from Day 3 through Day 7 in the Down-taper Period. Based on therapeutic response and tolerability, an additional dose increase to 80 mg/day was permitted at Week 3 of the Double-blind Treatment Period.
|
Fluoxetine 20 mg/Day
n=144 Participants
Fluoxetine capsule, orally, 10 mg/day at Week 1, and 20 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period followed by fluoxetine 10 mg/day from Day 1 through Day 7 of the Down-taper Period.
|
|---|---|---|---|
|
Change From Baseline in Children's Depression Rating Scale- Revised (CDRS-R)
|
-21.3 score on a scale
Standard Error 1.01
|
-23.0 score on a scale
Standard Error 1.01
|
-23.1 score on a scale
Standard Error 1.01
|
SECONDARY outcome
Timeframe: Baseline (Week 0) to Week 8Population: ITT Population included all participants in the Safety Population who had the Baseline and at least 1 post-baseline assessment of the Children's Depression Rating Scale-Revised (CDRS-R) total score. If a participant received an intervention different from the planned intervention, the participant is counted in the planned group. Overall number of participants analyzed are the number of participants with data available for analyses.
The CGI-S is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with MDD population. The participant was rated on a scale from 1 to 7, where 1=normal, not at all ill and 7=among the most extremely ill participants. Higher score indicates worsening of mental illness. A negative change from Baseline indicates improvement. MMRM was used for analysis.
Outcome measures
| Measure |
Placebo
n=146 Participants
Matching placebo capsules once daily through 8 weeks in the Double-blind Treatment Period and Days 1 through 7 in the Down-taper Period.
|
Levomilnacipran ER 40-80 mg/Day
n=148 Participants
Levomilnacipran ER capsules, orally, 10 mg/day on Days 1 to 3, 20 mg/day on Days 4 to 7, and 40 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period followed by levomilnacipran ER 40 mg/day on Days 1 and 2, and then 20 mg/day from Day 3 through Day 7 in the Down-taper Period. Based on therapeutic response and tolerability, an additional dose increase to 80 mg/day was permitted at Week 3 of the Double-blind Treatment Period.
|
Fluoxetine 20 mg/Day
n=144 Participants
Fluoxetine capsule, orally, 10 mg/day at Week 1, and 20 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period followed by fluoxetine 10 mg/day from Day 1 through Day 7 of the Down-taper Period.
|
|---|---|---|---|
|
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale
|
-1.5 score on a scale
Standard Error 0.10
|
-1.6 score on a scale
Standard Error 0.10
|
-1.7 score on a scale
Standard Error 0.10
|
Adverse Events
Placebo (Double-blind Treatment Period)
Serious events: 1 serious events
Other events: 32 other events
Deaths: 0 deaths
Levomilnacipran ER 40-80 mg/Day (Double-blind Treatment Period)
Serious events: 1 serious events
Other events: 44 other events
Deaths: 0 deaths
Fluoxetine 20 mg/Day (Double-blind Treatment Period)
Serious events: 4 serious events
Other events: 37 other events
Deaths: 0 deaths
Placebo (Down-taper Period)
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Levomilnacipran ER 40-80 mg/Day (Down-taper Period)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Fluoxetine 20 mg/Day (Down-taper Period)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo (Double-blind Treatment Period)
n=160 participants at risk
Matching placebo capsules once daily through 8 weeks in the Double-blind Treatment Period.
|
Levomilnacipran ER 40-80 mg/Day (Double-blind Treatment Period)
n=166 participants at risk
Levomilnacipran ER capsules, orally, 10 mg/day on Days 1 to 3, 20 mg/day on Days 4 to 7, and 40 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period. Based on therapeutic response and tolerability, an additional dose increase to 80 mg/day was permitted at Week 3 of the Double-blind Treatment Period.
|
Fluoxetine 20 mg/Day (Double-blind Treatment Period)
n=166 participants at risk
Fluoxetine capsule, orally, 10 mg/day at Week 1, and 20 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period.
|
Placebo (Down-taper Period)
n=160 participants at risk
Matching placebo capsules once daily on Days 1 through 7 in the Down-taper Period.
|
Levomilnacipran ER 40-80 mg/Day (Down-taper Period)
n=166 participants at risk
Levomilnacipran ER capsules, orally, 40 mg/day on Days 1 and 2, and then 20 mg/day from Day 3 through Day 7 in the Down-taper Period. Based on therapeutic response and tolerability, an additional dose increase to 80 mg/day was permitted at Week 3 of the Double-blind Treatment Period.
|
Fluoxetine 20 mg/Day (Down-taper Period)
n=166 participants at risk
Fluoxetine capsule, orally, 10 mg/day from Day 1 through Day 7 of the Down-taper Period.
|
|---|---|---|---|---|---|---|
|
Psychiatric disorders
Major depression
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.60%
1/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.62%
1/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
1.2%
2/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
|
Psychiatric disorders
Bipolar I disorder
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.60%
1/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
|
Psychiatric disorders
Intentional self-injury
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.60%
1/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
|
Psychiatric disorders
Suicide attempt
|
0.62%
1/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
Other adverse events
| Measure |
Placebo (Double-blind Treatment Period)
n=160 participants at risk
Matching placebo capsules once daily through 8 weeks in the Double-blind Treatment Period.
|
Levomilnacipran ER 40-80 mg/Day (Double-blind Treatment Period)
n=166 participants at risk
Levomilnacipran ER capsules, orally, 10 mg/day on Days 1 to 3, 20 mg/day on Days 4 to 7, and 40 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period. Based on therapeutic response and tolerability, an additional dose increase to 80 mg/day was permitted at Week 3 of the Double-blind Treatment Period.
|
Fluoxetine 20 mg/Day (Double-blind Treatment Period)
n=166 participants at risk
Fluoxetine capsule, orally, 10 mg/day at Week 1, and 20 mg/day from Week 2 through Week 8 of the Double-blind Treatment Period.
|
Placebo (Down-taper Period)
n=160 participants at risk
Matching placebo capsules once daily on Days 1 through 7 in the Down-taper Period.
|
Levomilnacipran ER 40-80 mg/Day (Down-taper Period)
n=166 participants at risk
Levomilnacipran ER capsules, orally, 40 mg/day on Days 1 and 2, and then 20 mg/day from Day 3 through Day 7 in the Down-taper Period. Based on therapeutic response and tolerability, an additional dose increase to 80 mg/day was permitted at Week 3 of the Double-blind Treatment Period.
|
Fluoxetine 20 mg/Day (Down-taper Period)
n=166 participants at risk
Fluoxetine capsule, orally, 10 mg/day from Day 1 through Day 7 of the Down-taper Period.
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
Tachycardia
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
6.0%
10/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
1.2%
2/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
|
Gastrointestinal disorders
Nausea
|
3.8%
6/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
9.6%
16/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
3.0%
5/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.62%
1/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.60%
1/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.60%
1/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.1%
5/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
6.6%
11/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
7.2%
12/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
|
Nervous system disorders
Headache
|
11.9%
19/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
12.7%
21/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
11.4%
19/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
1.2%
2/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
1.2%
2/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
|
Psychiatric disorders
Insomnia
|
5.6%
9/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
1.2%
2/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
3.0%
5/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/160 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.60%
1/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
0.00%
0/166 • Up to approximately 9 weeks
All-cause Mortality: All enrolled participants. Adverse Events: Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind investigational product. Data was collected and reported separately for the Double-blind Treatment Period and the Double-blind Down-taper Period.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
- Publication restrictions are in place
Restriction type: OTHER