Trial Outcomes & Findings for A Study for Assessing Treatment of Patients Ages 10-17 With Bipolar Depression (NCT NCT00844857)
NCT ID: NCT00844857
Last Updated: 2013-02-18
Results Overview
CDRS-R Total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. Least Square (LS) mean was adjusted for baseline, country, treatment, visit, and treatment times (\*) visit interaction.
COMPLETED
PHASE4
291 participants
Baseline, Week 8
2013-02-18
Participant Flow
Participant milestones
| Measure |
Olanzapine/Fluoxetine Combination
Olanzapine/fluoxetine Combination (OFC) 3 milligrams (mg) olanzapine and 25 mg fluoxetine (OFC 3/25) administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
Placebo
Matched placebo capsule administered orally once daily for 8 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
194
|
97
|
|
Overall Study
Population Analyzed
|
170
|
85
|
|
Overall Study
COMPLETED
|
116
|
60
|
|
Overall Study
NOT COMPLETED
|
78
|
37
|
Reasons for withdrawal
| Measure |
Olanzapine/Fluoxetine Combination
Olanzapine/fluoxetine Combination (OFC) 3 milligrams (mg) olanzapine and 25 mg fluoxetine (OFC 3/25) administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
Placebo
Matched placebo capsule administered orally once daily for 8 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
24
|
5
|
|
Overall Study
Sponsor Decision
|
1
|
1
|
|
Overall Study
Physician Decision
|
2
|
0
|
|
Overall Study
Parent/Caregiver Decision
|
6
|
2
|
|
Overall Study
Withdrawal by Subject
|
8
|
7
|
|
Overall Study
Protocol Violation
|
6
|
0
|
|
Overall Study
Lack of Efficacy
|
5
|
5
|
|
Overall Study
Clinical Relapse
|
0
|
1
|
|
Overall Study
Entry Criteria Not Met
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
3
|
|
Overall Study
Did Not Take Study Drug
|
3
|
1
|
|
Overall Study
Good Clinical Practice Violations
|
21
|
11
|
Baseline Characteristics
A Study for Assessing Treatment of Patients Ages 10-17 With Bipolar Depression
Baseline characteristics by cohort
| Measure |
Olanzapine/Fluoxetine Combination
n=170 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
Placebo
n=85 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Total
n=255 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
14.59 years
STANDARD_DEVIATION 2.30 • n=99 Participants
|
15.03 years
STANDARD_DEVIATION 2.13 • n=107 Participants
|
14.74 years
STANDARD_DEVIATION 2.25 • n=206 Participants
|
|
Sex: Female, Male
Female
|
86 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
125 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
84 Participants
n=99 Participants
|
46 Participants
n=107 Participants
|
130 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
123 participants
n=99 Participants
|
65 participants
n=107 Participants
|
188 participants
n=206 Participants
|
|
Region of Enrollment
Russian Federation
|
31 participants
n=99 Participants
|
13 participants
n=107 Participants
|
44 participants
n=206 Participants
|
|
Region of Enrollment
Mexico
|
16 participants
n=99 Participants
|
7 participants
n=107 Participants
|
23 participants
n=206 Participants
|
|
Ethnicity
Hispanic or Latino
|
38 participants
n=99 Participants
|
23 participants
n=107 Participants
|
61 participants
n=206 Participants
|
|
Ethnicity
Not Hispanic or Latino
|
132 participants
n=99 Participants
|
61 participants
n=107 Participants
|
193 participants
n=206 Participants
|
|
Ethnicity
Missing, participant did not reply
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Race
American Indian or Alaska Native
|
9 participants
n=99 Participants
|
5 participants
n=107 Participants
|
14 participants
n=206 Participants
|
|
Race
Asian
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
|
Race
Black or African American
|
23 participants
n=99 Participants
|
11 participants
n=107 Participants
|
34 participants
n=206 Participants
|
|
Race
Native Hawaiian or Other Pacific Islander
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Race
White
|
119 participants
n=99 Participants
|
61 participants
n=107 Participants
|
180 participants
n=206 Participants
|
|
Race
Multiple
|
15 participants
n=99 Participants
|
7 participants
n=107 Participants
|
22 participants
n=206 Participants
|
|
Race
Missing, participant did not reply
|
3 participants
n=99 Participants
|
1 participants
n=107 Participants
|
4 participants
n=206 Participants
|
|
Number of Previous Episodes of Mania During Participants Life
|
3.91 episodes
STANDARD_DEVIATION 10.43 • n=99 Participants
|
3.75 episodes
STANDARD_DEVIATION 5.69 • n=107 Participants
|
3.85 episodes
STANDARD_DEVIATION 9.12 • n=206 Participants
|
|
Number of Previous Episodes of Depression During Participants Life
|
4.63 episodes
STANDARD_DEVIATION 9.13 • n=99 Participants
|
4.11 episodes
STANDARD_DEVIATION 6.58 • n=107 Participants
|
4.45 episodes
STANDARD_DEVIATION 8.36 • n=206 Participants
|
|
Number of Previous Mixed Episodes During Participants Life
|
1.79 episodes
STANDARD_DEVIATION 7.69 • n=99 Participants
|
1.53 episodes
STANDARD_DEVIATION 3.96 • n=107 Participants
|
1.70 episodes
STANDARD_DEVIATION 6.68 • n=206 Participants
|
|
Number of Previous Episodes of Mania in Past 12 Months
|
1.26 episodes
STANDARD_DEVIATION 3.91 • n=99 Participants
|
1.27 episodes
STANDARD_DEVIATION 1.89 • n=107 Participants
|
1.27 episodes
STANDARD_DEVIATION 3.37 • n=206 Participants
|
|
Number of Previous Episodes of Depression in Past 12 Months
|
1.88 episodes
STANDARD_DEVIATION 4.16 • n=99 Participants
|
1.71 episodes
STANDARD_DEVIATION 2.31 • n=107 Participants
|
1.82 episodes
STANDARD_DEVIATION 3.64 • n=206 Participants
|
|
Number of Previous Mixed Episodes in Past 12 Months
|
0.68 episodes
STANDARD_DEVIATION 3.97 • n=99 Participants
|
0.39 episodes
STANDARD_DEVIATION 1.05 • n=107 Participants
|
0.58 episodes
STANDARD_DEVIATION 3.29 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the Modified Intention-to-Treat (M-ITT) Population: defined as all randomized participants who took at least 1 dose of study drug and excluding participants from 2 Good Clinical Practice (GCP) noncompliant sites and who had a baseline and at least 1 post-baseline CDRS-R measurement.
CDRS-R Total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. Least Square (LS) mean was adjusted for baseline, country, treatment, visit, and treatment times (\*) visit interaction.
Outcome measures
| Measure |
Placebo
n=84 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=170 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in the Children's Depression Rating Scale Revised (CDRS-R) Total Score at Week 8
|
-23.40 units on a scale
Standard Error 1.49
|
-28.43 units on a scale
Standard Error 1.13
|
SECONDARY outcome
Timeframe: Baseline up to Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites and who had both the CDRS-R, YMRS and CGI-BP total scores at baseline and at least 1 post-baseline measurement; Last Observation Carried Forward (LOCF)
Remission is defined as a CDRS-R total score less than or equal to (≤)28, and Young Mania Rating Scale (YMRS) total score ≤ 8 and Clinical Global Impressions-Bipolar Version (CGI-BP) total score ≤3. CDRS-R is a 17-item scale measuring presence/severity of depression in children and is scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. Scores range: 17 to 113. Scores \<20 indicate an absence of depression, scores 20 to 30 indicate borderline depression, scores 40 to 60 indicate moderate depression. The YMRS is an 11-item scale measuring severity of manic episodes; 4 items are rated on a scale from 0 (symptoms not present) to 8 (symptom extremely severe) with remaining items rated on a scale from 0 (symptoms not present) to 4 (symptom extremely severe). YMRS score ranges from 0 to 60. CGI-BP measures participant's overall severity of bipolar symptoms. Scores range: 1 (normal, not at all ill ) to 7 (among the most extremely ill participants).
Outcome measures
| Measure |
Placebo
n=76 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=156 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Percentage of Participants With Remission Up to Week 8
|
43.4 percentage of participants
|
59.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites and who had all of CDRS-R and YMRS total scores at baseline and at least 1 post-baseline measurement; LOCF
Response is defined as a CDRS-R total score greater than or equal to (≥)50% reduction from baseline and YMRS elevated mood score ≤2. CDRS-R Total score measure the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. Scores range: 17 to 113. In general, \<20 indicate an absence of depression, scores 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptoms not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptoms not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60.
Outcome measures
| Measure |
Placebo
n=76 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=156 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Percentage of Participants With Response Up to Week 8
|
59.2 percentage of participants
|
78.2 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites and who had both CDRS-R and YMRS total scores with a baseline and at least 1 post-baseline measurement; LOCF.
CDRS-R scores: No/low improvement is \< 25 percent (%) of maximum reduction from baseline. Mild improvement: maximum reduction from baseline on CDRS-R score ≥ 25% up to \<50% and YMRS elevated mood score ≤ 2. Moderate improvement: maximum reduction from baseline on CDRS-R score ≥50% and \<75% and YMRS elevated mood score ≤ 2. Major improvement: maximum reduction from baseline on CDRS-R score ≥75% and YMRS elevated mood score ≤ 2. CDRS-R measures presence/severity of depression in children. Scale is 17 items scored 1-to-5- or 1-to-7. Rating of 1 indicates normal function. Scores range: 17 to 113. Scores \< 20 absence of depression, scores 20 to 30 borderline depression, scores 40 to 60 indicate moderate depression. YMRS is an 11-item scale that measures severity of manic episodes. Four items rated 0 (symptoms not present) to 8 (symptom extremely severe). Remaining items rated 0 (symptoms not present) to 4 (symptom extremely severe). Score range: 0 to 60.
Outcome measures
| Measure |
Placebo
n=76 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=156 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Percentage of Participants in Each Improvement Category Up to Week 8
No or Low Improvement
|
22.4 percentage of participants
|
12.8 percentage of participants
|
|
Percentage of Participants in Each Improvement Category Up to Week 8
Mild Improvement
|
18.4 percentage of participants
|
9.0 percentage of participants
|
|
Percentage of Participants in Each Improvement Category Up to Week 8
Moderate Improvement
|
18.4 percentage of participants
|
21.8 percentage of participants
|
|
Percentage of Participants in Each Improvement Category Up to Week 8
Major Improvement
|
40.8 percentage of participants
|
56.4 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites who had YMRS total scores with a baseline and at least 1 post-baseline measurement.
The YMRS is an 11-item scale measuring the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total scores ranges: 0 to 60. LS mean was adjusted for baseline, country, treatment, visit, and treatment \* visit interaction.
Outcome measures
| Measure |
Placebo
n=60 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=118 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in the YMRS Total Score at Week 8
|
-1.57 units on a scale
Standard Error 0.63
|
-2.02 units on a scale
Standard Error 0.47
|
SECONDARY outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites and who had CGI-BP total scores at baseline and at least 1 post-baseline measurement.
CGI-BP measures severity of illness for bipolar illness. Scores range: 1 (normal, not ill at all) to 7 (among the most extremely ill patients). LS mean was adjusted for baseline, country, treatment, visit, and treatment \* visit interaction.
Outcome measures
| Measure |
Placebo
n=60 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=118 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in the Clinical Global Impression Scale - Bipolar Version (CGI-BP) Score at Week 8
|
-1.83 units on a scale
Standard Error 0.15
|
-2.21 units on a scale
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites who had CDRS-R total scores at baseline and at least 1 post-baseline measurement; LOCF.
CDRS-R Total score measure the presence and severity of depression in children and consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. Total scores range from 17 to 113. In general, scores \< 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. LS mean was adjusted for baseline, country, and treatment.
Outcome measures
| Measure |
Placebo
n=84 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=170 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in the CDRS-R Total Score Up to Week 8
|
-23.38 units on a scale
Standard Error 1.75
|
-28.57 units on a scale
Standard Error 1.41
|
SECONDARY outcome
Timeframe: Baseline up to Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug excluding participants from 2 GCP noncompliant sites; LOCF.
Akathisia was measured using the Barnes Akathisia Rating Scale where the global scores range from 0 (absent) to 5 (severe) and a score ≥ 2 is considered abnormal.
Outcome measures
| Measure |
Placebo
n=79 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=159 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Percentage of Participants With at Least One Treatment-Emergent Incident of Akathisia Up to Week 8
|
0.0 percentage of participants
|
1.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites; LOCF.
Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Percentage of participants with suicidal ideation, behavior, and acts are provided. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal act: a "yes" answer to actual attempt or completed suicide.
Outcome measures
| Measure |
Placebo
n=84 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=170 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Percentage of Participants With Treatment Emergent Suicidal Ideation or Behavior Up to Week 8
Total Suicidal Ideation (1 - 5)
|
15.5 percentage of participants
|
10.6 percentage of participants
|
|
Percentage of Participants With Treatment Emergent Suicidal Ideation or Behavior Up to Week 8
Total Suicidal Behavior (6 - 10)
|
2.4 percentage of participants
|
1.8 percentage of participants
|
|
Percentage of Participants With Treatment Emergent Suicidal Ideation or Behavior Up to Week 8
Total Suicidal Ideation or Behavior (1 - 10)
|
15.5 percentage of participants
|
10.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites with YMRS and CGI total scores at baseline and at least 1 post-baseline measurement; LOCF.
Worsening of mania was defined as YMRS score of ≥20 and a CGI severity of mania score of ≥ 5 at the same visit. The YMRS is an 11-item scale measuring severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe) with remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. CGI measures severity of the participant's overall severity of bipolar symptoms and scores range from 1 (normal) to 7 (among the most extremely ill participants).
Outcome measures
| Measure |
Placebo
n=84 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=170 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Percentage of Participants With at Least One Incident of Worsening of Mania Up to Week 8
|
0.0 percentage of participants
|
1.2 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites and ADHDRS-IV-PI results at baseline and at least 1 post-baseline measurement; LOCF.
Attention Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version (ADHDRS-IV-PI): Investigator Administered and Scored measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Scores range: 0 to 54. The LS mean was adjusted for baseline and treatment.
Outcome measures
| Measure |
Placebo
n=74 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=152 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in Symptoms of Attention-Deficit/Hyperactivity Disorder Up to Week 8
|
-3.57 units on a scale
Standard Error 1.00
|
-4.31 units on a scale
Standard Error 0.70
|
SECONDARY outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites and KINDL Parent Scale at baseline and at least 1 post-baseline measurement; LOCF.
The KINDL consists of 24 Likert-scale items. Total scores were standardized to a 0 (lowest quality of life) to 100 (highest quality of life). LS mean was adjusted for baseline, country, and treatment.
Outcome measures
| Measure |
Placebo
n=39 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=83 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in the Quality of Life Questionnaire for Children and Adolescents (KINDL) Parent Scale Up to Week 8
|
10.88 units on a scale
Standard Error 2.56
|
15.98 units on a scale
Standard Error 1.94
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites; LOCF.
Parkinsonism was measured using the Simpson-Angus Scale with a total scores range from 0 to 40. A score \> 3 was considered abnormal. Simpson-Angus Scale consists of 10 items, each rated on a 5-point scale, 0 (complete absence of the condition) to 4 (presence of the condition in extreme form).
Outcome measures
| Measure |
Placebo
n=80 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=158 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Percentage of Participants With at Least One Treatment-Emergent Incident of Parkinsonism Up to Week 8
|
1.3 percentage of participants
|
0.6 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites; LOCF.
Dyskinesia was measured using the Abnormal Involuntary Movement Scale (AIMS) a 12-item scale designed to record the occurrence of dyskinetic movements. Items 1 through 10 are rated on a 5-point scale: 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 11 and 12 are yes/no questions regarding the dental condition of a patient. Total score (0-40) is obtained by adding the scores of the first 10 items. An abnormal result is defined as having a score ≥3 for at least 1 of the first 7 items or a score ≥2 for at least two of the first 7 items.
Outcome measures
| Measure |
Placebo
n=80 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=160 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Percentage of Participants With at Least One Treatment-Emergent Incident of Dyskinesia Up to Week 8
|
0.0 percentage of participants
|
0.6 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug excluding participants from 2 GCP noncompliant sites and had KINDL Kid and Kiddo results at baseline and at least 1 post-baseline measurement. Due to small number of 10- and 11-year olds results from the 2 versions were pooled; LOCF.
The KINDL consists of 24 Likert-scale items. Kid-KINDL was administered to ages 8-11 and Kiddo-KINDL to ages 12-16. Total scores were standardized to a 0 (lowest quality of life) to 100 (highest quality of life). LS mean was adjusted for baseline, country, and treatment.
Outcome measures
| Measure |
Placebo
n=40 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=107 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in the Quality of Life Questionnaire for Children and Adolescents (KINDL) Kid and Kiddo Combined Scale Up to Week 8
|
7.91 units on a scale
Standard Error 2.40
|
12.83 units on a scale
Standard Error 1.65
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites and weight at baseline and at least 1 post-baseline measurement; LOCF.
Weight LS mean was adjusted for baseline and treatment.
Outcome measures
| Measure |
Placebo
n=84 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=170 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in Weight Up to Week 8
|
0.50 kilogram (kg)
Standard Error 0.33
|
4.37 kilogram (kg)
Standard Error 0.23
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug excluding participants from 2 GCP noncompliant sites and fasting glucose, cholesterol and triglycerides at baseline and at least 1 post-baseline measurement; LOCF.
Fasting glucose, fasting cholesterol and fasting triglycerides. LS means were adjusted for baseline and treatment.
Outcome measures
| Measure |
Placebo
n=81 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=158 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in Fasting Metabolic Parameters Up to Week 8
Fasting Glucose (157, 79)
|
0.03 millimoles/liter (mmol/L)
Standard Error 0.06
|
0.03 millimoles/liter (mmol/L)
Standard Error 0.04
|
|
Change From Baseline in Fasting Metabolic Parameters Up to Week 8
Fasting Cholesterol (158, 81)
|
-0.11 millimoles/liter (mmol/L)
Standard Error 0.07
|
0.42 millimoles/liter (mmol/L)
Standard Error 0.05
|
|
Change From Baseline in Fasting Metabolic Parameters Up to Week 8
Fasting Triglycerides (158, 81)
|
-0.04 millimoles/liter (mmol/L)
Standard Error 0.08
|
0.40 millimoles/liter (mmol/L)
Standard Error 0.06
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites and ALT/SGPT at baseline and at least 1 post-baseline measurement; LOCF.
ALT/SGPT LS mean was adjusted for baseline and treatment.
Outcome measures
| Measure |
Placebo
n=84 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=170 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in Alanine Aminotransferase/Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) Up to Week 8
|
0.46 units/Liter (U/L)
Standard Deviation 2.08
|
7.63 units/Liter (U/L)
Standard Deviation 1.46
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: Population analyzed was the M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites and prolactin at baseline and at least 1 post-baseline measurement; LOCF.
Prolactin LS mean was adjusted for baseline and treatment.
Outcome measures
| Measure |
Placebo
n=84 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=170 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in Prolactin Up to Week 8
|
0.70 microgram/Liter (μg/L)
Standard Error 1.10
|
8.66 microgram/Liter (μg/L)
Standard Error 0.77
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: Population analyzed M-ITT Population: all randomized participants who took at least 1 dose of study drug and excluding participants from 2 GCP noncompliant sites and QTcF at baseline and at least 1 post-baseline measurement; LOCF.
QTcF is defined as ECG QT interval corrected for heart rate using the Fridericia correction factor.
Outcome measures
| Measure |
Placebo
n=78 Participants
Matched placebo capsule administered orally once daily for 8 weeks.
|
Olanzapine/Fluoxetine Combination
n=158 Participants
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
|---|---|---|
|
Change From Baseline in Electrocardiogram (ECG) QTcF Interval Up to Week 8
|
-1.07 millisecond (msec)
Standard Error 1.44
|
8.19 millisecond (msec)
Standard Error 1.01
|
Adverse Events
Olanzapine/Fluoxetine Combination
Placebo
Serious adverse events
| Measure |
Olanzapine/Fluoxetine Combination
n=170 participants at risk
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
Placebo
n=85 participants at risk
Matched placebo capsule administered orally once daily for 8 weeks.
|
|---|---|---|
|
Immune system disorders
Anaphylaxis
|
0.00%
0/170
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
1.2%
1/85 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Infections and infestations
Pyoderma
|
0.00%
0/170
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
1.2%
1/85 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Psychiatric disorders
Aggression aggravated
|
1.2%
2/170 • Number of events 3
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
1.2%
1/85 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Psychiatric disorders
Agitation
|
0.59%
1/170 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
0.00%
0/85
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Psychiatric disorders
Bipolar affective disorder aggravated
|
0.59%
1/170 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
0.00%
0/85
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Psychiatric disorders
Depression worsened
|
0.00%
0/170
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
1.2%
1/85 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Psychiatric disorders
Homicidal ideation
|
0.59%
1/170 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
0.00%
0/85
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Psychiatric disorders
Psychosis aggravated
|
0.00%
0/170
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
1.2%
1/85 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Psychiatric disorders
Self injurious behavior
|
0.59%
1/170 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
0.00%
0/85
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Psychiatric disorders
Suicidal ideation
|
1.2%
2/170 • Number of events 2
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
1.2%
1/85 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Psychiatric disorders
Suicide attempt
|
0.59%
1/170 • Number of events 2
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
0.00%
0/85
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Reproductive system and breast disorders
Ovulation disorder
|
1.2%
1/86 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
0.00%
0/39
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
Other adverse events
| Measure |
Olanzapine/Fluoxetine Combination
n=170 participants at risk
OFC 3/25 mg administered orally as an initial dose beginning at randomization, 6/25 mg at Visit 3 (Day 3), 6/50 mg at Visit 4 (Week 1), and 12/50 mg at Visit 5 (Week 2). If no tolerability or safety issues occurred after Visit 5 the participant continued on the maximum tolerated dose, not to exceed 12/50 mg and not less than 6/25 mg, for a total of 8 weeks.
|
Placebo
n=85 participants at risk
Matched placebo capsule administered orally once daily for 8 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
4.7%
8/170 • Number of events 8
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
12.9%
11/85 • Number of events 13
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Gastrointestinal disorders
Vomiting
|
4.7%
8/170 • Number of events 8
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
5.9%
5/85 • Number of events 5
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Investigations
Triglyceride increased
|
5.3%
9/170 • Number of events 10
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
1.2%
1/85 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Investigations
Weight gain
|
18.8%
32/170 • Number of events 32
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
1.2%
1/85 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/170
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
5.9%
5/85 • Number of events 6
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Metabolism and nutrition disorders
Increased appetite
|
16.5%
28/170 • Number of events 28
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
1.2%
1/85 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Nervous system disorders
Drowsiness
|
5.3%
9/170 • Number of events 9
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
0.00%
0/85
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Nervous system disorders
Headache
|
14.1%
24/170 • Number of events 33
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
14.1%
12/85 • Number of events 16
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Nervous system disorders
Sedation
|
6.5%
11/170 • Number of events 12
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
0.00%
0/85
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Psychiatric disorders
Insomnia
|
2.4%
4/170 • Number of events 4
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
5.9%
5/85 • Number of events 5
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
1.2%
2/170 • Number of events 3
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
5.9%
5/85 • Number of events 5
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.59%
1/170 • Number of events 1
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
5.9%
5/85 • Number of events 5
Adverse events were reported for all randomized participants who took at least 1 dose of study drug, excluding 2 GCP noncompliant sites.
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60