Trial Outcomes & Findings for A Study of the Neurobiology of Depression (NCT NCT01051466)
NCT ID: NCT01051466
Last Updated: 2014-10-10
Results Overview
Functional MRI or fMRI is a functional neuroimaging procedure that uses MRI technology to measure brain activity by detecting associated changes in blood flow. When an area of the brain is in use, blood flow to that region increases. The activation in response to the processing of sad faces was measured by the percentage of signal change in BOLD response from before to after sad faces processing. The percentage of signal change was calculated by taking the difference between BOLD response after sad faces processing and BOLD response before sad faces processing and dividing by BOLD response before sad face processing, then multiplying by 100. BOLD signals were measured using arbitrary magnetic resonance units. Amygdala BOLD activation was calculated as an average between the left amygdala activation and right amygdala activation. Least squares (LS) mean was calculated using mixed-model repeated measures (MMRM) adjusted for group, visit, group-by-visit, and baseline value.
COMPLETED
PHASE4
60 participants
Baseline, Week 12
2014-10-10
Participant Flow
Participant milestones
| Measure |
Duloxetine
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Overall Study
STARTED
|
32
|
28
|
|
Overall Study
COMPLETED
|
24
|
23
|
|
Overall Study
NOT COMPLETED
|
8
|
5
|
Reasons for withdrawal
| Measure |
Duloxetine
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
5
|
1
|
|
Overall Study
Entry Criteria Not Met
|
0
|
3
|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
A Study of the Neurobiology of Depression
Baseline characteristics by cohort
| Measure |
Duloxetine
n=32 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=28 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.21 years
STANDARD_DEVIATION 11.23 • n=5 Participants
|
39.19 years
STANDARD_DEVIATION 9.41 • n=7 Participants
|
39.74 years
STANDARD_DEVIATION 10.35 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
18 participants
n=5 Participants
|
16 participants
n=7 Participants
|
34 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
10 participants
n=5 Participants
|
4 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
4 participants
n=5 Participants
|
8 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
32 participants
n=5 Participants
|
28 participants
n=7 Participants
|
60 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Enrolled participants who had baseline and at least 1 post-baseline activation (BOLD response) observation.
Functional MRI or fMRI is a functional neuroimaging procedure that uses MRI technology to measure brain activity by detecting associated changes in blood flow. When an area of the brain is in use, blood flow to that region increases. The activation in response to the processing of sad faces was measured by the percentage of signal change in BOLD response from before to after sad faces processing. The percentage of signal change was calculated by taking the difference between BOLD response after sad faces processing and BOLD response before sad faces processing and dividing by BOLD response before sad face processing, then multiplying by 100. BOLD signals were measured using arbitrary magnetic resonance units. Amygdala BOLD activation was calculated as an average between the left amygdala activation and right amygdala activation. Least squares (LS) mean was calculated using mixed-model repeated measures (MMRM) adjusted for group, visit, group-by-visit, and baseline value.
Outcome measures
| Measure |
Duloxetine
n=28 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=28 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Change From Baseline to 12-Week Endpoint in the Functional Magnetic Resonance Imaging (fMRI) Mean Blood Oxygenation-Level-Dependent (BOLD) Response in the Amygdalae
|
-0.01 percentage of signal change
Standard Error 0.13
|
-0.16 percentage of signal change
Standard Error 0.13
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Enrolled participants who had baseline and at least 1 post-baseline activation (BOLD response) observation, excluding 3 healthy participants who did not meet entry criteria.
Functional magnetic resonance imaging (fMRI) is a functional neuroimaging procedure that uses MRI technology to measure brain activity by detecting associated changes in blood flow. When an area of the brain is in use, blood flow to that region increases. The activation in response to the processing of sad faces in each brain region (anterior cingulate, left amygdala and right amygdala) was measured by the percentage of signal change in BOLD response. The percentage of signal change was calculated by taking the difference between BOLD response after sad faces processing and BOLD response before sad faces processing and dividing by BOLD response before sad face processing, then multiplying by 100. BOLD signals were measured using arbitrary magnetic resonance units. Least squares (LS) mean was calculated using mixed-model repeated measures (MMRM) adjusted for group, visit, group-by-visit, and baseline value.
Outcome measures
| Measure |
Duloxetine
n=28 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=25 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Change From Baseline to 12-Week Endpoint in Activation [Blood Oxygenation-Level-Dependent (BOLD) Response to Implicit Processing of Sad Faces] for Each of the 3 Brain Regions
Anterior Cingulate
|
0.13 percentage of signal change
Standard Error 0.09
|
0.20 percentage of signal change
Standard Error 0.09
|
|
Change From Baseline to 12-Week Endpoint in Activation [Blood Oxygenation-Level-Dependent (BOLD) Response to Implicit Processing of Sad Faces] for Each of the 3 Brain Regions
Left Amygdala
|
-0.04 percentage of signal change
Standard Error 0.16
|
-0.26 percentage of signal change
Standard Error 0.16
|
|
Change From Baseline to 12-Week Endpoint in Activation [Blood Oxygenation-Level-Dependent (BOLD) Response to Implicit Processing of Sad Faces] for Each of the 3 Brain Regions
Right Amygdala
|
0.03 percentage of signal change
Standard Error 0.12
|
-0.09 percentage of signal change
Standard Error 0.12
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Enrolled participants who had baseline and at least 1 post-baseline observation for the volume of specific brain regions, excluding 3 healthy participants who did not meet entry criteria.
The volume of specific brain regions is obtained using a structural magnetic resonance imaging (sMRI) procedure in which high-resolution spoiled gradient recall images are acquired in coronal brain slices. Least squares (LS) mean was calculated using mixed-model repeated measures (MMRM) adjusted for group, visit, group-by-visit, and baseline value.
Outcome measures
| Measure |
Duloxetine
n=28 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=24 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Change From Baseline to 12-Week Endpoint in Volume of Subgenual Anterior Cingulate, Amygdalae, and Hippocampus
Subgenual Anterior Cingulate
|
-188.27 cubic millimeters (mm^3)
Standard Error 112.37
|
175.22 cubic millimeters (mm^3)
Standard Error 116.14
|
|
Change From Baseline to 12-Week Endpoint in Volume of Subgenual Anterior Cingulate, Amygdalae, and Hippocampus
Left Amygdalae
|
-23.68 cubic millimeters (mm^3)
Standard Error 15.25
|
4.20 cubic millimeters (mm^3)
Standard Error 15.59
|
|
Change From Baseline to 12-Week Endpoint in Volume of Subgenual Anterior Cingulate, Amygdalae, and Hippocampus
Right Amygdalae
|
-33.38 cubic millimeters (mm^3)
Standard Error 17.83
|
23.86 cubic millimeters (mm^3)
Standard Error 18.40
|
|
Change From Baseline to 12-Week Endpoint in Volume of Subgenual Anterior Cingulate, Amygdalae, and Hippocampus
Left Hippocampus
|
-13.56 cubic millimeters (mm^3)
Standard Error 23.53
|
18.52 cubic millimeters (mm^3)
Standard Error 24.37
|
|
Change From Baseline to 12-Week Endpoint in Volume of Subgenual Anterior Cingulate, Amygdalae, and Hippocampus
Right Hippocampus
|
-14.70 cubic millimeters (mm^3)
Standard Error 19.19
|
21.80 cubic millimeters (mm^3)
Standard Error 19.66
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1, 8, and 12Population: Enrolled participants who had a baseline and at least 1 post-baseline Gsα localization observation, excluding 3 healthy participants who did not meet entry criteria. No participants were analyzed for the translocation of Gsα from lipid rafts in the cell membranes of WBCs.
Gsα is a membrane-associated protein that couples receptors for neurotransmitters like serotonin to allow them to send messages between nerve cells - a process that may be altered during depression and antidepressant treatment. Gsα localization in the cholesterol-rich (lipid rafts) and cholesterol-poor regions of cell membranes of RBCs and platelets was measured with quantitative Western blots and reported as the ratio of Gsα (absorbance units) in Triton X-100 (TX-100) over Triton X-114 (TX-114), 2 detergents that discriminate between lipid raft and non-raft membrane domains. Translocation of Gsα was measured as the change from baseline in Gsα localization. Translocation of Gsα from lipid rafts in the cell membranes of WBCs was not analyzed due to technical laboratory issues. Least squares (LS) mean was calculated using mixed-model repeated measures (MMRM) adjusted for group, visit, group-by-visit, and baseline value.
Outcome measures
| Measure |
Duloxetine
n=23 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=22 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Translocation of Gs Alpha (Gsα) From Lipid Rafts in the Cell Membranes of Red Blood Cells (RBCs), White Blood Cells (WBCs) and Platelets Compared With Baseline
RBCs, Week 1 (n=23, 22)
|
0.51 Ratio
Standard Error 0.21
|
0.09 Ratio
Standard Error 0.22
|
|
Translocation of Gs Alpha (Gsα) From Lipid Rafts in the Cell Membranes of Red Blood Cells (RBCs), White Blood Cells (WBCs) and Platelets Compared With Baseline
RBCs, Week 8 (n=23, 22)
|
-0.01 Ratio
Standard Error 0.14
|
-0.15 Ratio
Standard Error 0.14
|
|
Translocation of Gs Alpha (Gsα) From Lipid Rafts in the Cell Membranes of Red Blood Cells (RBCs), White Blood Cells (WBCs) and Platelets Compared With Baseline
RBCs, Week 12 (n=23, 22)
|
0.36 Ratio
Standard Error 0.26
|
0.10 Ratio
Standard Error 0.26
|
|
Translocation of Gs Alpha (Gsα) From Lipid Rafts in the Cell Membranes of Red Blood Cells (RBCs), White Blood Cells (WBCs) and Platelets Compared With Baseline
Platelets, Week 1 (n=23, 20)
|
-0.63 Ratio
Standard Error 0.46
|
-0.69 Ratio
Standard Error 0.49
|
|
Translocation of Gs Alpha (Gsα) From Lipid Rafts in the Cell Membranes of Red Blood Cells (RBCs), White Blood Cells (WBCs) and Platelets Compared With Baseline
Platelets, Week 8 (n=23, 20)
|
-1.16 Ratio
Standard Error 0.42
|
-0.92 Ratio
Standard Error 0.44
|
|
Translocation of Gs Alpha (Gsα) From Lipid Rafts in the Cell Membranes of Red Blood Cells (RBCs), White Blood Cells (WBCs) and Platelets Compared With Baseline
Platelets, Week 12 (n=23, 20)
|
-0.52 Ratio
Standard Error 5.40
|
7.93 Ratio
Standard Error 5.40
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 8, and 12Population: No participants were analyzed.
Gsα is a membrane-associated protein that couples receptors for neurotransmitters like serotonin to allow them to send messages between nerve cells - a process that may be altered during depression and antidepressant treatment. Adenylyl cyclase is activated by Gsα, and when Gsα is translocated from lipid rafts it more effectively activates adenylyl cyclase. Gsα-activated adenylyl cyclase was not analyzed due to technical laboratory issues.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Enrolled participants who had baseline and at least 1 post-baseline BDNF or proBDNF observation, excluding 3 healthy participants who did not meet entry criteria.
There is evidence that stress may decrease BDNF expression, while antidepressant treatment reverses or blocks these effects. BDNF is a protein that occurs naturally and supports the survival and growth of some nerve cells in the brain. proBDNF is a precursor of BDNF. Least squares (LS) mean was calculated using mixed-model repeated measures (MMRM) adjusted for group, visit, group-by-visit, and baseline value.
Outcome measures
| Measure |
Duloxetine
n=23 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=21 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Change From Baseline to 12-Week Endpoint in Brain-Derived Neurotrophic Factor (BDNF) and the Precursor of BDNF (proBDNF)
BDNF (n=23, 21)
|
6.61 nanograms per milliliter (ng/mL)
Standard Error 23.38
|
10.57 nanograms per milliliter (ng/mL)
Standard Error 22.80
|
|
Change From Baseline to 12-Week Endpoint in Brain-Derived Neurotrophic Factor (BDNF) and the Precursor of BDNF (proBDNF)
proBDNF (n=13, 17)
|
-5.67 nanograms per milliliter (ng/mL)
Standard Error 12.77
|
-9.37 nanograms per milliliter (ng/mL)
Standard Error 9.36
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Enrolled participants who had baseline and at least 1 post-baseline trkB observation, excluding 3 healthy participants who did not meet entry criteria. No participant was analyzed for the change from baseline in p75NTR receptors.
There is evidence that stress may decrease BDNF expression, while antidepressant treatment reverses or blocks these effects. BDNF is a protein that occurs naturally and supports the survival and growth of some nerve cells in the brain. proBDNF is a precursor of BDNF. Tropomyosin receptor kinase B (trkB) is a receptor for BDNF, and pan-neurotrophin receptor p75 (p75NTR) is a receptor for proBDNF. p75NTR was not analyzed due to technical laboratory issues. Least squares (LS) mean was calculated using mixed-model repeated measures (MMRM) adjusted for group, visit, group-by-visit, and baseline value.
Outcome measures
| Measure |
Duloxetine
n=24 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=21 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Change From Baseline to 12-Week Endpoint in Brain-Derived Neurotrophic Factor (BDNF) and the Precursor of BDNF (proBDNF) Receptors
|
52.1 picograms per milligram (pg/mg)
Standard Error 41.08
|
-8.9 picograms per milligram (pg/mg)
Standard Error 36.25
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Enrolled participants who had baseline and at least 1 post-baseline cytokine observation (TNFα, IL-1, or IL-6), excluding 3 healthy participants who did not meet entry criteria.
Cytokines are naturally produced and regulate responses to inflammation. Proinflammatory cytokines like TNFα, IL-1, and IL-6 increase inflammation in the body. Least squares (LS) mean was calculated using mixed-model repeated measures (MMRM) adjusted for group, visit, group-by-visit, and baseline value.
Outcome measures
| Measure |
Duloxetine
n=28 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=22 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Change From Baseline to 12-Week Endpoint in Proinflammatory Cytokines [Tumor Necrosis Factor Alpha (TNFα), Interleukin 1 (IL-1), and Interleukin 6 (IL-6)]
Cytokine TNFα
|
-0.04 picograms per milliliter (pg/mL)
Standard Error 0.78
|
0.25 picograms per milliliter (pg/mL)
Standard Error 0.81
|
|
Change From Baseline to 12-Week Endpoint in Proinflammatory Cytokines [Tumor Necrosis Factor Alpha (TNFα), Interleukin 1 (IL-1), and Interleukin 6 (IL-6)]
Cytokine IL-1
|
-0.08 picograms per milliliter (pg/mL)
Standard Error 2.53
|
4.01 picograms per milliliter (pg/mL)
Standard Error 2.64
|
|
Change From Baseline to 12-Week Endpoint in Proinflammatory Cytokines [Tumor Necrosis Factor Alpha (TNFα), Interleukin 1 (IL-1), and Interleukin 6 (IL-6)]
Cytokine IL-6
|
-0.61 picograms per milliliter (pg/mL)
Standard Error 0.69
|
-0.52 picograms per milliliter (pg/mL)
Standard Error 0.71
|
SECONDARY outcome
Timeframe: Baseline and up to Week 12Population: Enrolled participants who had a baseline and at least 1 post-baseline HAMD17 observation. Last observation carried forward (LOCF) was utilized when calculating the Week 12 endpoint outcome.
The HAMD17 is a standardized instrument consisting of 17 items used to measure the severity of major depressive disorder (MDD) and improvements in depression symptoms. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Higher scores indicated greater symptom severity. The total score was the sum of the scores from HAMD17 Items 1 through 17 and could have ranged from 0 (not at all depressed) to 52 (severely depressed).
Outcome measures
| Measure |
Duloxetine
n=29 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=14 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
17-Item Hamilton Depression Rating Scale (HAMD17)
Baseline
|
22.4 units on a scale
Standard Deviation 2.66
|
0.5 units on a scale
Standard Deviation 1.34
|
|
17-Item Hamilton Depression Rating Scale (HAMD17)
Week 12
|
8.5 units on a scale
Standard Deviation 6.60
|
0.5 units on a scale
Standard Deviation 1.40
|
SECONDARY outcome
Timeframe: Baseline, up to Week 12Population: Enrolled MDD participants who had a baseline and at least 1 post-baseline HAMD17 observation. Last observation carried forward (LOCF) was utilized when calculating the Week 12 endpoint outcome.
HAMD17 response is defined as a \>50% reduction in HAMD17 total score from baseline. The HAMD17 is a standardized instrument consisting of 17 items used to measure the severity of major depressive disorder (MDD) and improvements in depression symptoms. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Higher scores indicated greater symptom severity. The total score was the sum of the scores from HAMD17 Items 1 through 17 and could have ranged from 0 (not at all depressed) to 52 (severely depressed). The percentage of participants with a HAMD17 response was calculated as the number of participants with a \>50% reduction in HAMD17 total score from baseline divided by the number of participants who had a HAMD17 observation at Week 12 then multiplied by 100.
Outcome measures
| Measure |
Duloxetine
n=29 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Percentage of Participants With 17-Item Hamilton Depression Rating Scale (HAMD17) Response
|
72.4 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, up to Week 12Population: Enrolled MDD participants who had a baseline and at least 1 post-baseline HAMD17 observation. Last observation carried forward (LOCF) was utilized when calculating the Week 12 endpoint outcome.
HAMD17 remission is defined as a HAMD17 total score of ≤7 at Week 12 (endpoint). The HAMD17 is a standardized instrument consisting of 17 items used to measure the severity of major depressive disorder (MDD) and improvements in depression symptoms. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Higher scores indicated greater symptom severity. The total score was the sum of the scores from HAMD17 Items 1 through 17 and could have ranged from 0 (not at all depressed) to 52 (severely depressed). The percentage of participants with remission was calculated as the number of participants with a HAMD17 total score of ≤7 divided by the number of participants who had a HAMD17 observation at Week 12 then multiplied by 100.
Outcome measures
| Measure |
Duloxetine
n=29 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Percentage of Participants With 17-Item Hamilton Depression Rating Scale (HAMD17) Remission
|
62.1 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline and up to Week 12Population: Enrolled participants who had baseline and at least 1 post-baseline SDS observation. Last observation carried forward (LOCF) was utilized when calculating the Week 12 endpoint outcome.
The SDS is a participant-rated questionnaire used to assess the effect of the participant's symptoms on work/school (Item 1), social life/leisure activities (Item 2), and family/home management (Item 3). Each item was rated on a visual analog scale (VAS) from 0 (not at all) to 10 (very severely). The SDS Global Functional Impairment Score (SDS Global Score) was the sum of the 3 items and could have ranged from 0 (unimpaired) to 30 (highly impaired). Higher values indicated higher functional impairment in the participant's work/social/family life.
Outcome measures
| Measure |
Duloxetine
n=27 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=25 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Sheehan Disability Scale (SDS)
Baseline
|
19.3 units on a scale
Standard Deviation 5.41
|
0.2 units on a scale
Standard Deviation 0.80
|
|
Sheehan Disability Scale (SDS)
Week 12
|
9.4 units on a scale
Standard Deviation 7.72
|
0.0 units on a scale
Standard Deviation 0.00
|
SECONDARY outcome
Timeframe: Baseline and up to Week 12Population: Enrolled participants who had baseline and at least 1 post-baseline CGI-S observation. Last observation carried forward (LOCF) was utilized when calculating the Week 12 endpoint outcome.
The CGI-S measures severity of illness at the time of assessment. Scores can range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Outcome measures
| Measure |
Duloxetine
n=29 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=25 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Clinical Global Impressions of Severity Scale (CGI-S)
Baseline
|
4.4 units on a scale
Standard Deviation 0.56
|
1.0 units on a scale
Standard Deviation 0.00
|
|
Clinical Global Impressions of Severity Scale (CGI-S)
Week 12
|
2.2 units on a scale
Standard Deviation 1.08
|
1.0 units on a scale
Standard Deviation 0.00
|
SECONDARY outcome
Timeframe: Baseline, up to Week 12Population: Enrolled MDD participants who had at least 1 post-baseline PGI-I observation. Last observation carried forward (LOCF) was utilized when calculating the Week 12 endpoint outcome. PGI-I observations were not completed for healthy participants.
The PGI-I scale measures the participant's perception of improvement at the time of assessment compared with the start of treatment. Scores can range from 1 (very much better) to 7 (very much worse).
Outcome measures
| Measure |
Duloxetine
n=29 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Patient's Global Impressions of Improvement (PGI-I) Scale
|
2.6 units on a scale
Standard Deviation 1.24
|
—
|
SECONDARY outcome
Timeframe: Baseline and up to Week 12Population: Enrolled participants who had a baseline and at least 1 post-baseline HAMA observation. Last observation carried forward (LOCF) was utilized when calculating the Week 12 endpoint outcome.
The 14-item HAMA is used to assess the severity of anxiety. The investigator talked to the participant about their symptoms over the previous week. Each item was scored using a 5-point scale (0 = not present to 4 = very severe). Total HAMA scores could have ranged from 0 (normal) to 56 (severe).
Outcome measures
| Measure |
Duloxetine
n=29 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
n=25 Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Hamilton Anxiety Rating Scale (HAMA)
Baseline
|
21.1 units on a scale
Standard Deviation 5.78
|
0.4 units on a scale
Standard Deviation 0.87
|
|
Hamilton Anxiety Rating Scale (HAMA)
Week 12
|
9.6 units on a scale
Standard Deviation 7.25
|
0.4 units on a scale
Standard Deviation 0.96
|
SECONDARY outcome
Timeframe: Baseline through Week 12Population: Participants with MDD who had a baseline and at least 1 post-baseline C-SSRS assessment. Healthy participants did not have a C-SSRS assessment post baseline.
The C-SSRS captures the occurrence, severity, and frequency of treatment-emergent suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a "yes" answer to any 1 of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Treatment-emergent outcomes were the worsening or new occurrence of suicidal behaviors or ideation during treatment compared with baseline.
Outcome measures
| Measure |
Duloxetine
n=29 Participants
Duloxetine: Participants with major depressive disorder (MDD), who successfully completed screening, received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose. At study completion, participants could optionally complete a 2-week dose down-titration taper.
|
Healthy Participants
Healthy participants: Participants who successfully completed screening, were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Incidence of Suicidal Behavior and Suicidal Ideation as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
Treatment-emergent suicidal ideation
|
5 participants
|
—
|
|
Incidence of Suicidal Behavior and Suicidal Ideation as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
Treatment-emergent suicidal behavior
|
0 participants
|
—
|
Adverse Events
Duloxetine
Healthy Participants
Serious adverse events
| Measure |
Duloxetine
n=32 participants at risk
Duloxetine: Participants with major depressive disorder (MDD) received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose.
|
Healthy Participants
n=28 participants at risk
Healthy participants: Participants were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Eye disorders
Retinal pigment epitheliopathy
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
Other adverse events
| Measure |
Duloxetine
n=32 participants at risk
Duloxetine: Participants with major depressive disorder (MDD) received 60 milligrams (mg) up to 120 mg orally, once daily (QD) for 12 weeks. The initial starting dose was 60 mg duloxetine QD for the first 8 weeks. Then, remitters \[defined as participants with a 17-item Hamilton Depression Rating Scale (HAMD17) total score ≤7\] continued on 60 mg duloxetine QD, while non-remitters (HAMD17 total score \>7) could have their duloxetine dose flexed between 60 mg QD up to 120 mg QD, based on the clinical judgment of the Principal Investigator and tolerability of the participant to the dose.
|
Healthy Participants
n=28 participants at risk
Healthy participants: Participants were matched by age, gender, and intelligence quotient (IQ) to participants with MDD. IQ was measured by the Wechsler Adult Intelligence Scale - Third United Kingdom Edition (WAIS-III UK). Healthy participants did not receive study drug.
|
|---|---|---|
|
Blood and lymphatic system disorders
Microcytic anaemia
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Cardiac disorders
Palpitations
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Ear and labyrinth disorders
Motion sickness
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Ear and labyrinth disorders
Tinnitus
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Endocrine disorders
Hypothyroidism
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Eye disorders
Eye pain
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Eye disorders
Eye pruritus
|
0.00%
0/32
|
3.6%
1/28 • Number of events 1
|
|
Eye disorders
Lacrimation increased
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Eye disorders
Vision blurred
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Gastrointestinal disorders
Abdominal discomfort
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Gastrointestinal disorders
Abdominal distension
|
3.1%
1/32 • Number of events 1
|
3.6%
1/28 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
21.9%
7/32 • Number of events 7
|
0.00%
0/28
|
|
Gastrointestinal disorders
Diarrhoea
|
21.9%
7/32 • Number of events 7
|
0.00%
0/28
|
|
Gastrointestinal disorders
Dry mouth
|
25.0%
8/32 • Number of events 8
|
0.00%
0/28
|
|
Gastrointestinal disorders
Dyspepsia
|
6.2%
2/32 • Number of events 2
|
3.6%
1/28 • Number of events 1
|
|
Gastrointestinal disorders
Epigastric discomfort
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
0.00%
0/32
|
3.6%
1/28 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
62.5%
20/32 • Number of events 23
|
0.00%
0/28
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Gastrointestinal disorders
Vomiting
|
21.9%
7/32 • Number of events 9
|
0.00%
0/28
|
|
General disorders
Asthenia
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
General disorders
Chest pain
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
General disorders
Fatigue
|
18.8%
6/32 • Number of events 6
|
0.00%
0/28
|
|
General disorders
Feeling hot
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
General disorders
Influenza like illness
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
General disorders
Irritability
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
General disorders
Pyrexia
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
General disorders
Sluggishness
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
General disorders
Thirst
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Immune system disorders
Allergy to animal
|
0.00%
0/32
|
3.6%
1/28 • Number of events 1
|
|
Immune system disorders
Seasonal allergy
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Infections and infestations
Ear infection
|
3.1%
1/32 • Number of events 1
|
3.6%
1/28 • Number of events 2
|
|
Infections and infestations
Gastroenteritis
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Infections and infestations
Nasopharyngitis
|
15.6%
5/32 • Number of events 7
|
10.7%
3/28 • Number of events 3
|
|
Infections and infestations
Viral upper respiratory tract infection
|
3.1%
1/32 • Number of events 2
|
0.00%
0/28
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Injury, poisoning and procedural complications
Procedural dizziness
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Injury, poisoning and procedural complications
Procedural pain
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Injury, poisoning and procedural complications
Tendon injury
|
0.00%
0/32
|
3.6%
1/28 • Number of events 1
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Investigations
Alanine aminotransferase increased
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Investigations
Aspartate aminotransferase increased
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Investigations
Blood alkaline phosphatase increased
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Investigations
Blood creatine phosphokinase increased
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Investigations
Gamma-glutamyltransferase increased
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Investigations
Gastric ph decreased
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Metabolism and nutrition disorders
Decreased appetite
|
28.1%
9/32 • Number of events 9
|
0.00%
0/28
|
|
Metabolism and nutrition disorders
Food craving
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Metabolism and nutrition disorders
Increased appetite
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.4%
3/32 • Number of events 4
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.2%
2/32 • Number of events 2
|
3.6%
1/28 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.1%
1/32 • Number of events 2
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Nervous system disorders
Balance disorder
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Nervous system disorders
Disturbance in attention
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Nervous system disorders
Dizziness
|
28.1%
9/32 • Number of events 11
|
0.00%
0/28
|
|
Nervous system disorders
Dysgeusia
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Nervous system disorders
Headache
|
34.4%
11/32 • Number of events 18
|
14.3%
4/28 • Number of events 8
|
|
Nervous system disorders
Hypersomnia
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Nervous system disorders
Myoclonus
|
3.1%
1/32 • Number of events 2
|
0.00%
0/28
|
|
Nervous system disorders
Nervous system disorder
|
0.00%
0/32
|
3.6%
1/28 • Number of events 1
|
|
Nervous system disorders
Paraesthesia
|
6.2%
2/32 • Number of events 3
|
0.00%
0/28
|
|
Nervous system disorders
Somnolence
|
12.5%
4/32 • Number of events 5
|
0.00%
0/28
|
|
Nervous system disorders
Syncope
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Nervous system disorders
White matter lesion
|
0.00%
0/32
|
3.6%
1/28 • Number of events 1
|
|
Psychiatric disorders
Abnormal dreams
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Psychiatric disorders
Anorgasmia
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Psychiatric disorders
Anxiety
|
9.4%
3/32 • Number of events 3
|
0.00%
0/28
|
|
Psychiatric disorders
Bruxism
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Psychiatric disorders
Insomnia
|
28.1%
9/32 • Number of events 9
|
0.00%
0/28
|
|
Psychiatric disorders
Libido decreased
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Psychiatric disorders
Obsessive-compulsive disorder
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Psychiatric disorders
Sleep disorder
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Psychiatric disorders
Suicidal ideation
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Renal and urinary disorders
Chromaturia
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Renal and urinary disorders
Dysuria
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Renal and urinary disorders
Micturition disorder
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Renal and urinary disorders
Pollakiuria
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Renal and urinary disorders
Urinary hesitation
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Reproductive system and breast disorders
Ejaculation delayed
|
5.3%
1/19 • Number of events 1
|
0.00%
0/14
|
|
Reproductive system and breast disorders
Ejaculation disorder
|
5.3%
1/19 • Number of events 1
|
0.00%
0/14
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
5.3%
1/19 • Number of events 1
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
0.00%
0/32
|
3.6%
1/28 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.00%
0/32
|
3.6%
1/28 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Yawning
|
21.9%
7/32 • Number of events 7
|
0.00%
0/28
|
|
Skin and subcutaneous tissue disorders
Eczema
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.2%
2/32 • Number of events 2
|
0.00%
0/28
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
3.1%
1/32 • Number of events 1
|
0.00%
0/28
|
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