Trial Outcomes & Findings for A Study of Olanzapine and Fluoxetine for Treatment-resistant Depression (NCT NCT01687478)
NCT ID: NCT01687478
Last Updated: 2019-10-09
Results Overview
The MADRS total score is the sum of the 10 items; therefore the possible MADRS total score ranges from 0 to 60. A higher MADRS total score indicates a greater severity of depressive symptoms. Least square means (LSM) change from baseline, standard error was derived using mixed model repeated measures (MMRM) methodology with factors for treatment, Pooled Investigator, Visit, (Baseline + Treatment)\*Visit.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
176 participants
Primary outcome timeframe
Baseline, 8 Weeks
Results posted on
2019-10-09
Participant Flow
Participant milestones
| Measure |
Olanzapine + Fluoxetine
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
88
|
88
|
|
Overall Study
Safety Analysis Set
|
88
|
87
|
|
Overall Study
COMPLETED
|
56
|
49
|
|
Overall Study
NOT COMPLETED
|
32
|
39
|
Reasons for withdrawal
| Measure |
Olanzapine + Fluoxetine
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
10
|
|
Overall Study
Lost to Follow-up
|
1
|
3
|
|
Overall Study
Protocol Violation
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
21
|
19
|
|
Overall Study
Physician Decision
|
1
|
3
|
|
Overall Study
Entry Criteria Not Met
|
6
|
2
|
Baseline Characteristics
A Study of Olanzapine and Fluoxetine for Treatment-resistant Depression
Baseline characteristics by cohort
| Measure |
Olanzapine + Fluoxetine
n=88 Participants
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=88 Participants
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Total
n=176 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.63 years
STANDARD_DEVIATION 12.18 • n=5 Participants
|
41.45 years
STANDARD_DEVIATION 12.44 • n=7 Participants
|
40.04 years
STANDARD_DEVIATION 12.36 • n=5 Participants
|
|
Sex: Female, Male
Female
|
41 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
88 Participants
n=5 Participants
|
88 Participants
n=7 Participants
|
176 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
88 Participants
n=5 Participants
|
88 Participants
n=7 Participants
|
176 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
China
|
88 participants
n=5 Participants
|
88 participants
n=7 Participants
|
176 participants
n=5 Participants
|
|
Montgomery-Äsberg Depression Rating Scale (MADRS) Total Score
|
32.1 units on a scale
STANDARD_DEVIATION 5.3 • n=5 Participants
|
31.8 units on a scale
STANDARD_DEVIATION 4.8 • n=7 Participants
|
32.0 units on a scale
STANDARD_DEVIATION 5.0 • n=5 Participants
|
|
17 Item Hamilton Rating Scale for Depression (HAM-D17) Total Score
|
24.6 units on a scale
STANDARD_DEVIATION 2.6 • n=5 Participants
|
25.0 units on a scale
STANDARD_DEVIATION 2.6 • n=7 Participants
|
24.8 units on a scale
STANDARD_DEVIATION 2.6 • n=5 Participants
|
|
Clinical Global Impressions-Severity of Depression (CGI-S)
|
4.9 units on a scale
STANDARD_DEVIATION 0.6 • n=5 Participants
|
4.9 units on a scale
STANDARD_DEVIATION 0.7 • n=7 Participants
|
4.9 units on a scale
STANDARD_DEVIATION 0.7 • n=5 Participants
|
|
Age of First Major Depressive Disorder (MDD) Episode
|
29.92 years
STANDARD_DEVIATION 12.61 • n=5 Participants
|
34.07 years
STANDARD_DEVIATION 12.69 • n=7 Participants
|
30.00 years
STANDARD_DEVIATION 12.79 • n=5 Participants
|
|
Years Since the First MDD Episode
|
8.71 years
STANDARD_DEVIATION 6.21 • n=5 Participants
|
7.38 years
STANDARD_DEVIATION 7.86 • n=7 Participants
|
8.05 years
STANDARD_DEVIATION 7.10 • n=5 Participants
|
|
Years Since the Most Recent MDD Episode
|
3.66 years
STANDARD_DEVIATION 5.12 • n=5 Participants
|
3.23 years
STANDARD_DEVIATION 4.15 • n=7 Participants
|
3.45 years
STANDARD_DEVIATION 4.65 • n=5 Participants
|
|
Number of Previous Lifetime MDD Episodes
|
1.4 Number of MDD Episodes
STANDARD_DEVIATION 1.4 • n=5 Participants
|
1.3 Number of MDD Episodes
STANDARD_DEVIATION 2.1 • n=7 Participants
|
1.3 Number of MDD Episodes
STANDARD_DEVIATION 1.8 • n=5 Participants
|
|
Number of Previous MDD Episodes Within the Last 36 Months
|
0.5 Number of MDD Episodes
STANDARD_DEVIATION 0.8 • n=5 Participants
|
0.5 Number of MDD Episodes
STANDARD_DEVIATION 1.1 • n=7 Participants
|
0.5 Number of MDD Episodes
STANDARD_DEVIATION 0.9 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 8 WeeksPopulation: Participants in the full analysis set (FAS) population: all randomized participants who had a baseline and at least one post-baseline MADRS total score measurement.
The MADRS total score is the sum of the 10 items; therefore the possible MADRS total score ranges from 0 to 60. A higher MADRS total score indicates a greater severity of depressive symptoms. Least square means (LSM) change from baseline, standard error was derived using mixed model repeated measures (MMRM) methodology with factors for treatment, Pooled Investigator, Visit, (Baseline + Treatment)\*Visit.
Outcome measures
| Measure |
Olanzapine + Fluoxetine
n=87 Participants
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=86 Participants
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Mean Change From Baseline to 8 Week Endpoint in Montgomery-Äsberg Depression Rating Scale (MADRS)
|
-15.92 Units on a scale
Standard Error 1.20
|
-14.30 Units on a scale
Standard Error 1.28
|
SECONDARY outcome
Timeframe: Baseline, 8 WeeksPopulation: Participants in the FAS population: all randomized participants who had a baseline and at least one post-baseline MADRS total score measurement.
CGI-S scale measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The LS mean (LSM) change from baseline, standard error was derived using MMRM methodology with factors for treatment , Pooled Investigator , Visit , (Baseline + Treatment)\*Visit.
Outcome measures
| Measure |
Olanzapine + Fluoxetine
n=87 Participants
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=86 Participants
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Mean Change From Baseline to 8 Week Endpoint in Clinical Global Impressions-Severity of Depression (CGI-S) Scale
|
-1.43 Units on a scale
Standard Error 0.15
|
-1.63 Units on a scale
Standard Error 0.16
|
SECONDARY outcome
Timeframe: Baseline, 8 WeeksPopulation: All randomized participants who received at least one dose of study drug.
SAS scale consists of 10 items including 7 items that address bradykinesia-rigidity and additional single items for tremor, glabellar tap,and salivation. Each item represents a specific physical condition and is rated on a 5-point category rating scale ranging from 0 (complete absence of the condition) to 4 (the condition is present to an extreme degree).The total score is obtained by adding the scores for the 10 individual items making the maximum possible score is 40. Higher scores are indicative of more severe Parkinsonian-type symptoms.
Outcome measures
| Measure |
Olanzapine + Fluoxetine
n=88 Participants
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=87 Participants
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Mean Change From Baseline to 8 Week Endpoint in the Simpson-Angus Scale (SAS)
|
0.03 units on a scale
Standard Deviation 1.71
|
-0.14 units on a scale
Standard Deviation 1.72
|
SECONDARY outcome
Timeframe: Baseline, 8 WeeksPopulation: All randomized participants.
SF-36, version 2 is a generic participant-rated questionnaire and consists of 36 questions covering the following 8 health domains (subscales): general health, role limitations because of physical problems, role limitations due to emotional problems, physical functioning, bodily pain, mental health, social functioning, and vitality. Each subscale is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. Two summary scores, the physical component summary (PCS) and the mental component summary (MCS) were constructed based on the eight SF-36 subscales. Both PCS and MCS range from 0-100 with higher scores indicating better health or functioning.
Outcome measures
| Measure |
Olanzapine + Fluoxetine
n=88 Participants
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=88 Participants
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)
Physical Functioning
|
2.20 units on a scale
Standard Deviation 7.51
|
0.70 units on a scale
Standard Deviation 7.47
|
|
Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)
Role-Physical
|
3.99 units on a scale
Standard Deviation 11.79
|
3.93 units on a scale
Standard Deviation 11.23
|
|
Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)
Bodily Pain
|
6.81 units on a scale
Standard Deviation 12.05
|
0.02 units on a scale
Standard Deviation 11.30
|
|
Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)
General Health
|
5.82 units on a scale
Standard Deviation 11.49
|
2.84 units on a scale
Standard Deviation 9.44
|
|
Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)
Vitality
|
7.43 units on a scale
Standard Deviation 13.54
|
5.04 units on a scale
Standard Deviation 9.83
|
|
Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)
Social Functioning
|
6.13 units on a scale
Standard Deviation 13.55
|
4.56 units on a scale
Standard Deviation 11.78
|
|
Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)
Role-Emotional
|
6.61 units on a scale
Standard Deviation 12.39
|
6.71 units on a scale
Standard Deviation 12.12
|
|
Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)
Mental Health
|
8.98 units on a scale
Standard Deviation 13.46
|
8.43 units on a scale
Standard Deviation 11.99
|
|
Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)
Mental Component Score
|
8.87 units on a scale
Standard Deviation 14.29
|
8.73 units on a scale
Standard Deviation 12.54
|
|
Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)
Physical Component Score
|
2.87 units on a scale
Standard Deviation 7.59
|
-0.65 units on a scale
Standard Deviation 7.22
|
SECONDARY outcome
Timeframe: Baseline, 8 WeeksPopulation: All randomized participants.
SDS consists of 3 items (work/school, social life/leisure activities, and family life/home responsibilities). Total scores range from 0 to 30 with higher values indicating greater disruption. Individual Item scores range from 0 to 10 with higher values indicating greater disruption.
Outcome measures
| Measure |
Olanzapine + Fluoxetine
n=88 Participants
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=88 Participants
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Mean Change From Baseline to 8 Week Endpoint in the Sheehan Disability Scale (SDS)
SDS Total Score (68,64)
|
-4.57 Units on a scale
Standard Error 7.75
|
-4.41 Units on a scale
Standard Error 7.89
|
|
Mean Change From Baseline to 8 Week Endpoint in the Sheehan Disability Scale (SDS)
Work/School (n=68,65)
|
-1.34 Units on a scale
Standard Error 2.71
|
-1.55 Units on a scale
Standard Error 2.89
|
|
Mean Change From Baseline to 8 Week Endpoint in the Sheehan Disability Scale (SDS)
Social Life (n=79,79)
|
-1.70 Units on a scale
Standard Error 2.66
|
-1.49 Units on a scale
Standard Error 2.85
|
|
Mean Change From Baseline to 8 Week Endpoint in the Sheehan Disability Scale (SDS)
Family Life (n=79,78)
|
-1.63 Units on a scale
Standard Error 3.00
|
-1.53 Units on a scale
Standard Error 2.66
|
SECONDARY outcome
Timeframe: Baseline,8 WeeksPopulation: All randomized participants who had a baseline and at least one post-baseline MADRS total score measurement.
The MADRS total score is the sum of the 10 items; therefore the possible MADRS total score ranges from 0 to 60. A higher MADRS total score indicates a greater severity of depressive symptoms.
Outcome measures
| Measure |
Olanzapine + Fluoxetine
n=87 Participants
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=86 Participants
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Percentage of Participants Who Achieve a Response Based on a ≥50% Reduction From Baseline in MADRS Total Score
|
65.5 Percent of participants
|
61.2 Percent of participants
|
SECONDARY outcome
Timeframe: Baseline, 8 WeeksPopulation: All randomized participants who had a baseline and at least one post-baseline MADRS total score measurement.
The MADRS consists of 10 items with each item rated on a scale ranging from 0 to 6. Fixed descriptors appear along the scale for each item at points 0, 2, 4, and 6, to standardize the gradation of response along the scale. The MADRS total score is the sum of the 10 items; therefore the possible MADRS total score ranges from 0 to 60. A higher MADRS total score indicates a greater severity of depressive symptoms.
Outcome measures
| Measure |
Olanzapine + Fluoxetine
n=87 Participants
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=86 Participants
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Percentage of Participants Who Achieve Remission Based on MADRS Total Score ≤10 at 8 Weeks
|
37.9 Percent of participants
|
38.8 Percent of participants
|
SECONDARY outcome
Timeframe: Baseline, 8 WeeksPopulation: All randomized participants who received at least one dose of study drug.
BAS is used to rate observable, restless movements of drug induced akathisia and the subjective awareness of restlessness and any distress associated with the akathisia. The BAS consists of the following 3 items: an objective assessment of akathisia symptoms; a subjective assessment of the patient's awareness of inner restlessness; and a global clinical assessment of akathisia. The first two items are rated on a 4-point scale ranging from 0 (no abnormal movements or the absence of inner restlessness) to 3 (severe akathisia or the awareness of intense compulsion to move most of the time). The last item, the global clinical assessment of akathisia, is rated on a 5-point scale, ranging from 0 (no evidence of akathisia) to 5 (severe akathisia). Total BAS score ranges from 0 to 14 with a higher score representing worse results.
Outcome measures
| Measure |
Olanzapine + Fluoxetine
n=88 Participants
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=87 Participants
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Mean Change From Baseline to 8 Week Endpoint in the Barnes Akathisia Scale (BAS)
|
-0.01 units on a scale
Standard Deviation 2.24
|
-0.04 units on a scale
Standard Deviation 2.13
|
SECONDARY outcome
Timeframe: Baseline, 8 WeeksPopulation: All randomized participants who received at least one dose of study drug.
AIMS is a 12-item scale. Items 1 to 8 are rated on a 5-point scale ranging from 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Item 9 assesses the participant's incapacitation due to abnormal movements, and item 10 assesses the participant's awareness of the abnormal movements and associated distress. Items 9 and 10 are rated on 5-point scales ranging from 0 (none or no awareness) to 4 (severe or aware, severe distress). Items 11 and 12 are yes/no questions regarding the dental status of the participant. The total score is the sum of the scores for the 12 items and the possible total score ranges from 0 to 42. A higher total score is indicative of more severe dyskinetic movements.
Outcome measures
| Measure |
Olanzapine + Fluoxetine
n=88 Participants
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=87 Participants
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Mean Change From Baseline to 8 Week Endpoint in the Abnormal Involuntary Movement Scale (AIMS)
|
-0.16 units on a scale
Standard Deviation 1.47
|
-0.31 units on a scale
Standard Deviation 3.28
|
Adverse Events
Olanzapine + Fluoxetine
Serious events: 1 serious events
Other events: 55 other events
Deaths: 0 deaths
Placebo + Fluoxetine
Serious events: 1 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Olanzapine + Fluoxetine
n=88 participants at risk
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=87 participants at risk
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Psychiatric disorders
Restlessness
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
Other adverse events
| Measure |
Olanzapine + Fluoxetine
n=88 participants at risk
Olanzapine starting dose is 5 milligram (mg). May titrate up to 10 mg, or 15 mg administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
Placebo + Fluoxetine
n=87 participants at risk
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
|
|---|---|---|
|
Cardiac disorders
Angina pectoris
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Cardiac disorders
Cardiovascular insufficiency
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Cardiac disorders
Palpitations
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
2.3%
2/87 • Number of events 2
All participants in the safety analysis set.
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Cardiac disorders
Supraventricular extrasystoles
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Cardiac disorders
Tachycardia
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Ear and labyrinth disorders
Tinnitus
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Eye disorders
Vision blurred
|
2.3%
2/88 • Number of events 2
All participants in the safety analysis set.
|
2.3%
2/87 • Number of events 2
All participants in the safety analysis set.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/88
All participants in the safety analysis set.
|
2.3%
2/87 • Number of events 2
All participants in the safety analysis set.
|
|
Gastrointestinal disorders
Dry mouth
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Gastrointestinal disorders
Haematochezia
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/88
All participants in the safety analysis set.
|
4.6%
4/87 • Number of events 4
All participants in the safety analysis set.
|
|
Gastrointestinal disorders
Retching
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Gastrointestinal disorders
Tongue disorder
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
General disorders
Asthenia
|
2.3%
2/88 • Number of events 2
All participants in the safety analysis set.
|
3.4%
3/87 • Number of events 3
All participants in the safety analysis set.
|
|
General disorders
Chest discomfort
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
2.3%
2/87 • Number of events 2
All participants in the safety analysis set.
|
|
General disorders
Chest pain
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
General disorders
Discomfort
|
0.00%
0/88
All participants in the safety analysis set.
|
2.3%
2/87 • Number of events 2
All participants in the safety analysis set.
|
|
General disorders
Fatigue
|
3.4%
3/88 • Number of events 3
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
General disorders
Gait disturbance
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
General disorders
Hunger
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
General disorders
Oedema
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
General disorders
Sensation of foreign body
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
General disorders
Thirst
|
2.3%
2/88 • Number of events 2
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
6.8%
6/88 • Number of events 6
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Hepatobiliary disorders
Liver disorder
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Hepatobiliary disorders
Liver injury
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Infections and infestations
Nasopharyngitis
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Infections and infestations
Upper respiratory tract infection
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Injury, poisoning and procedural complications
Skin injury
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Investigations
Alanine aminotransferase increased
|
8.0%
7/88 • Number of events 7
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Investigations
Aspartate aminotransferase increased
|
5.7%
5/88 • Number of events 5
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Investigations
Blood bilirubin increased
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
2.3%
2/87 • Number of events 2
All participants in the safety analysis set.
|
|
Investigations
Blood cholesterol increased
|
5.7%
5/88 • Number of events 5
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Investigations
Blood creatine phosphokinase increased
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Investigations
Blood glucose increased
|
2.3%
2/88 • Number of events 2
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Investigations
Blood pressure increased
|
2.3%
2/88 • Number of events 2
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Investigations
Blood prolactin increased
|
10.2%
9/88 • Number of events 9
All participants in the safety analysis set.
|
2.3%
2/87 • Number of events 2
All participants in the safety analysis set.
|
|
Investigations
Blood triglycerides increased
|
8.0%
7/88 • Number of events 7
All participants in the safety analysis set.
|
3.4%
3/87 • Number of events 3
All participants in the safety analysis set.
|
|
Investigations
Electrocardiogram abnormal
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Investigations
Electrocardiogram t wave abnormal
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Investigations
Gamma-glutamyltransferase increased
|
3.4%
3/88 • Number of events 3
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Investigations
High density lipoprotein decreased
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Investigations
Lipids increased
|
3.4%
3/88 • Number of events 3
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Investigations
Low density lipoprotein increased
|
3.4%
3/88 • Number of events 3
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Investigations
Transaminases increased
|
3.4%
3/88 • Number of events 3
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Investigations
Weight decreased
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
4.6%
4/87 • Number of events 4
All participants in the safety analysis set.
|
|
Investigations
Weight increased
|
9.1%
8/88 • Number of events 8
All participants in the safety analysis set.
|
2.3%
2/87 • Number of events 2
All participants in the safety analysis set.
|
|
Investigations
White blood cell count decreased
|
0.00%
0/88
All participants in the safety analysis set.
|
2.3%
2/87 • Number of events 2
All participants in the safety analysis set.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
2.3%
2/88 • Number of events 2
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
4.5%
4/88 • Number of events 4
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Metabolism and nutrition disorders
Increased appetite
|
6.8%
6/88 • Number of events 6
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/41
All participants in the safety analysis set.
|
2.9%
1/35 • Number of events 1
All participants in the safety analysis set.
|
|
Nervous system disorders
Akathisia
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Nervous system disorders
Dizziness
|
3.4%
3/88 • Number of events 3
All participants in the safety analysis set.
|
5.7%
5/87 • Number of events 5
All participants in the safety analysis set.
|
|
Nervous system disorders
Extrapyramidal disorder
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Nervous system disorders
Headache
|
2.3%
2/88 • Number of events 2
All participants in the safety analysis set.
|
3.4%
3/87 • Number of events 3
All participants in the safety analysis set.
|
|
Nervous system disorders
Hypokinesia
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Nervous system disorders
Somnolence
|
17.0%
15/88 • Number of events 17
All participants in the safety analysis set.
|
3.4%
3/87 • Number of events 4
All participants in the safety analysis set.
|
|
Nervous system disorders
Syncope
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Nervous system disorders
Tremor
|
1.1%
1/88 • Number of events 2
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Psychiatric disorders
Dysphoria
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Psychiatric disorders
Fear
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Psychiatric disorders
Initial insomnia
|
0.00%
0/88
All participants in the safety analysis set.
|
2.3%
2/87 • Number of events 2
All participants in the safety analysis set.
|
|
Psychiatric disorders
Insomnia
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Psychiatric disorders
Mental disorder
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Psychiatric disorders
Nervousness
|
2.3%
2/88 • Number of events 2
All participants in the safety analysis set.
|
2.3%
2/87 • Number of events 3
All participants in the safety analysis set.
|
|
Psychiatric disorders
Restlessness
|
2.3%
2/88 • Number of events 2
All participants in the safety analysis set.
|
3.4%
3/87 • Number of events 3
All participants in the safety analysis set.
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Psychiatric disorders
Somatic delusion
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Psychiatric disorders
Suicidal ideation
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Renal and urinary disorders
Urine odour abnormal
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
0.00%
0/87
All participants in the safety analysis set.
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
0.00%
0/88
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
2.3%
2/88 • Number of events 2
All participants in the safety analysis set.
|
3.4%
3/87 • Number of events 3
All participants in the safety analysis set.
|
|
Vascular disorders
Hypertension
|
1.1%
1/88 • Number of events 1
All participants in the safety analysis set.
|
1.1%
1/87 • Number of events 1
All participants in the safety analysis set.
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60