Duloxetine Versus Placebo in the Treatment of Patients With Diabetic Peripheral Neuropathic Pain in China
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00408993
Collaborator
Boehringer Ingelheim (Industry)
215
7
2
14
30.7
2.2
Study Details
Study Description
Brief Summary
To determine if duloxetine 60mg up to 120mg daily can work in treating pain from Diabetic Neuropathy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
215 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Duloxetine Versus Placebo in the Treatment of Patients With Diabetic Peripheral Neuropathic Pain in China
Study Start Date
:
Dec 1, 2006
Actual Primary Completion Date
:
Feb 1, 2008
Actual Study Completion Date
:
Feb 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Duloxetine 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) |
Drug: Duloxetine Hydrochloride
60 mg every day (QD) (morning or evening), by mouth (PO)
Other Names:
|
| Placebo Comparator: Placebo Placebo every day (QD), by mouth (PO) for 12 weeks |
Drug: Placebo
Placebo every day (QD), by mouth (PO)
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline to 12 Week Endpoint in Brief Pain Inventory 24-hour Average Pain Score [Baseline and 12 weeks]
A self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Secondary Outcome Measures
- Change From Baseline to 12 Week Endpoint in Brief Pain Inventory (BPI) Worst Pain, Least Pain, and Current Pain Severity and Average Interference Scores [Baseline and 12 weeks]
Measures severity of pain and interference of pain on function. Each severity of pain (worst, least, and current) scores range from 0 (no pain) to 10 (pain as severe as you can imagine). The 7 separate Interference item scores range from 0 (does not interfere) to 10 (completely interferes) and were averaged to provide a single score (0 to 10).
- Change From Baseline to 12 Week Endpoint in Clinical Global Impression of Severity [Baseline and 12 weeks]
Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients.
- Time Course of Change in Patient Global Impression - Improvement Scale [baseline, over 12 weeks]
A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).
- Change From Baseline to 12 Week Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) (US Based Index Score) [Baseline and 12 weeks]
The EQ-5D is an assessment of one's overall health. Consists of 5 items. Patients choose 1 of 3 options that best describe the status of each item. The EQ-5D US based index scores range from -0.11 to 1.0 where a score of 1.0 indicates perfect health. A positive change from baseline indicates health improvement.
- Number of Participants Discontinuing Due to Adverse Events [over 12 weeks]
- Number of Participants With Treatment-Emergent Adverse Events Reported in >5% of Either Treatment Group by Time of Dosing (Morning or Evening) [over 12 weeks]
Tolerability of morning versus evening dosing, as assessed by the number of participants with spontaneously reported adverse events.
- Change From Baseline to 12 Week Endpoint in Athens Insomnia Scale 8-item and 5-item [Baseline and 12 weeks]
Estimates sleep difficulty. Consists of 8 items rated on a 4-point scale of 0 (no problem at all) to 3 (very serious problem). Total score of the 8-item version (sum of items 1-8) ranges from 0-24, while total score of the 5-item (sum of items 1-5) ranges from 0-15.
- Vital Signs - Weight [Baseline and 12 weeks]
Change from baseline to endpoint in body weight.
- Vital Signs - Pulse Rate [Baseline and 12 weeks]
Change from baseline to endpoint in pulse rate.
- Vital Signs - Blood Pressure [Baseline and 12 weeks]
Change from baseline to endpoint in systolic and diastolic blood pressure.
- Statistically Significant Change From Baseline to 12 Week Endpoint in Laboratory Measures - Chloride, High Density Lipoprotein, Sodium, and Triglycerides [Baseline and 12 weeks]
Significantly different laboratory values between the two groups in baseline to endpoint changes in chloride, high density lipoprotein, sodium, and triglycerides.
- Statistically Significant Change From Baseline to 12 Week Endpoint in Laboratory Measures - Uric Acid [Baseline and 12 weeks]
Significantly different laboratory values between the two groups in baseline to endpoint changes
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have pain due to bilateral peripheral neuropathy caused by Type I or Type II diabetes with the pain beginning in the feet and present for at least 6 months.
-
May not be pregnant and agree to utilize medically acceptable and reliable means of birth control during participation in the study.
-
Score of 4 or greater on the Brief Pain Inventory on the 24-hour average pain item.
Exclusion Criteria:
-
Glycosylated hemoglobin (A1C) > 12%
-
Severe hepatic disease
-
History of substance abuse or dependence within the past year, excluding nicotine and caffeine.
-
Serious or unstable cardiovascular, hepatic (acute liver injury such as hepatitis or severe cirrhosis), kidney, respiratory, blood disorder, seizure disorder, problems with peripheral vascular disease, or other medical conditions or psychiatric conditions that would hinder your participation or likely to lead to hospitalization during the course of the study.
-
Taking monoamine oxidase inhibitor (MAOI) within 14 days of starting the study or the potential need to take during or within 5 days after discontinuation from the study.
-
Treatment of fluoxetine within 30 days of starting the study.
-
Unstable blood sugar control and uncontrolled or poorly controlled hypertension.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Beijing | China | 100101 | |
| 2 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Changsha | China | 410011 | |
| 3 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Harbin | China | 150086 | |
| 4 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Nanjing | China | 210029 | |
| 5 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Nanjin | China | 210012 | |
| 6 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Shanghai | China | 200233 | |
| 7 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Wu Han | China | 430022 |
Sponsors and Collaborators
- Eli Lilly and Company
- Boehringer Ingelheim
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri from 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00408993
Other Study ID Numbers:
- 10599
- F1J-MC-HMEQ(a)
First Posted:
Dec 8, 2006
Last Update Posted:
Jul 26, 2011
Last Verified:
Jul 1, 2011
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Period Title: Overall Study | ||
| STARTED | 106 | 109 |
| COMPLETED | 87 | 92 |
| NOT COMPLETED | 19 | 17 |
Baseline Characteristics
| Arm/Group Title | Duloxetine | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks | Total of all reporting groups |
| Overall Participants | 106 | 109 | 215 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
58.59
(10.37)
|
59.90
(9.52)
|
59.25
(9.94)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
55
51.9%
|
59
54.1%
|
114
53%
|
| Male |
51
48.1%
|
50
45.9%
|
101
47%
|
| Region of Enrollment (participants) [Number] | |||
| China |
106
100%
|
109
100%
|
215
100%
|
| Major Depressive Disorder (participants) [Number] | |||
| No |
89
84%
|
88
80.7%
|
177
82.3%
|
| Yes |
17
16%
|
21
19.3%
|
38
17.7%
|
| Race/Ethnicity (participants) [Number] | |||
| East Asian |
106
100%
|
109
100%
|
215
100%
|
| Type of Diabetes Mellitus (participants) [Number] | |||
| Type I Diabetes Mellitus |
3
2.8%
|
2
1.8%
|
5
2.3%
|
| Type II Diabetes Mellitus |
103
97.2%
|
107
98.2%
|
210
97.7%
|
| Beck Depression Inventory-II Total Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
15.97
(10.66)
|
15.27
(11.49)
|
15.61
(11.07)
|
| Brief Pain Inventory 24-Hour Average Pain Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
5.47
(1.31)
|
5.52
(1.39)
|
5.50
(1.35)
|
| Clinical Global Impressions of Severity Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
4.26
(0.76)
|
4.38
(0.91)
|
4.32
(0.84)
|
| Diabetic Neuropathy History (years) [Mean (Standard Deviation) ] | |||
| Duration of Diabetes |
9.07
(6.32)
|
10.21
(6.91)
|
9.65
(6.63)
|
| Duration of Diabetic Neuropathy |
2.13
(2.60)
|
2.50
(2.98)
|
2.32
(2.80)
|
| Duration of Diabetic Peripheral Neuropathic Pain |
3.09
(3.11)
|
3.34
(3.36)
|
3.22
(3.24)
|
| Height (centimeters) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [centimeters] |
162.64
(7.72)
|
162.12
(7.96)
|
162.37
(7.83)
|
| Michigan Neuropathy Screening Instrument (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
4.45
(1.19)
|
4.59
(1.19)
|
4.52
(1.19)
|
| Weight (kilograms) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kilograms] |
64.06
(10.62)
|
63.25
(11.52)
|
63.65
(11.07)
|
Outcome Measures
| Title | Change From Baseline to 12 Week Endpoint in Brief Pain Inventory 24-hour Average Pain Score |
|---|---|
| Description | A self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline value. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 104 | 109 |
| Least Squares Mean (Standard Error) [units on a scale] |
-2.69
(0.19)
|
-2.31
(0.18)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | With 104 patients per arm, the study has at least 85% power to detect a treatment group difference of -1.20 points in baseline to endpoint mean change on the BPI 24-hour average pain score between Duloxetine and Placebo. Sample size determined using a two-sided t-test with alpha=0.05, and assuming a common standard deviation of 2.5 and a discontinuation rate of 25%. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.617 |
| Comments | Treatment effects were evaluated based on a two-sided significance level of 0.05 and interaction effects at 0.10. No adjustments for multiple comparisons were made. | |
| Method | ANCOVA | |
| Comments | Model=Treatment, Pooled Investigator and Baseline. | |
| Title | Change From Baseline to 12 Week Endpoint in Brief Pain Inventory (BPI) Worst Pain, Least Pain, and Current Pain Severity and Average Interference Scores |
|---|---|
| Description | Measures severity of pain and interference of pain on function. Each severity of pain (worst, least, and current) scores range from 0 (no pain) to 10 (pain as severe as you can imagine). The 7 separate Interference item scores range from 0 (does not interfere) to 10 (completely interferes) and were averaged to provide a single score (0 to 10). |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline value. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 104 | 109 |
| Worst Pain Score |
-3.48
(0.27)
|
-2.93
(0.26)
|
| Least Pain Score |
-1.69
(0.20)
|
-1.37
(0.20)
|
| Pain Right Now Score |
-2.72
(0.26)
|
-1.99
(0.25)
|
| Average Interference Score |
-2.28
(0.21)
|
-1.88
(0.20)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.070 |
| Comments | P-value for Worst Pain Score | |
| Method | ANCOVA | |
| Comments | Model=Treatment, Pooled Investigator, Baseline and Major Depressive Disorder status at baseline. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.151 |
| Comments | P-value for Least Pain Score | |
| Method | ANCOVA | |
| Comments | Model=Treatment, Pooled Investigator, Baseline and Major Depressive Disorder status at baseline. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.012 |
| Comments | P-value for Pain Right Now Score | |
| Method | ANCOVA | |
| Comments | Model=Treatment, Pooled Investigator, Baseline and Major Depressive Disorder status at baseline. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.077 |
| Comments | P-value for Average Interference Score | |
| Method | ANCOVA | |
| Comments | Model=Treatment, Pooled Investigator, Baseline and Major Depressive Disorder status at baseline. | |
| Title | Change From Baseline to 12 Week Endpoint in Clinical Global Impression of Severity |
|---|---|
| Description | Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients. |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline value. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 103 | 109 |
| Least Squares Mean (Standard Error) [units on a scale] |
-1.24
(0.11)
|
-0.99
(0.11)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.036 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Model=Treatment, Pooled Investigator, Baseline and Major Depressive Disorder status at baseline. | |
| Title | Time Course of Change in Patient Global Impression - Improvement Scale |
|---|---|
| Description | A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). |
| Time Frame | baseline, over 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat analysis. Number of randomized patients with at least one non-missing post-baseline data. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 98 | 107 |
| Week 1 (N=5, N=2) |
3.45
(0.56)
|
3.51
(0.88)
|
| Week 2 (N=98, N=107) |
2.91
(0.09)
|
3.23
(0.09)
|
| Week 4 (N=94, N=101) |
2.57
(0.10)
|
2.83
(0.10)
|
| Week 8 (N=91, N=95) |
2.29
(0.11)
|
2.76
(0.11)
|
| Week 12 (N=87, N=92) |
2.27
(0.11)
|
2.58
(0.11)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.955 |
| Comments | P-value for Visit 3 | |
| Method | Mixed Models Analysis | |
| Comments | Repeated Measures: Model=Treatment, Pooled Investigator, Visit, Baseline, baseline MDD status, Treatment*Visit and Baseline*Visit. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | P-value for Visit 4 | |
| Method | Mixed Models Analysis | |
| Comments | Repeated Measures: Model=Treatment, Pooled Investigator, Visit, Baseline, baseline MDD status, Treatment*Visit and Baseline*Visit. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.037 |
| Comments | P-value for Visit 5 | |
| Method | Mixed Models Analysis | |
| Comments | Repeated Measures: Model=Treatment, Pooled Investigator, Visit, Baseline, baseline MDD status, Treatment*Visit and Baseline*Visit. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | P-value for Visit 6 | |
| Method | Mixed Models Analysis | |
| Comments | Repeated Measures: Model=Treatment, Pooled Investigator, Visit, Baseline, baseline MDD status, Treatment*Visit and Baseline*Visit. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.028 |
| Comments | P-value for Visit 7 | |
| Method | Mixed Models Analysis | |
| Comments | Repeated Measures: Model=Treatment, Pooled Investigator, Visit, Baseline, baseline MDD status, Treatment*Visit and Baseline*Visit. | |
| Title | Change From Baseline to 12 Week Endpoint in EuroQoL Questionnaire - 5 Dimensions (EQ-5D) (US Based Index Score) |
|---|---|
| Description | The EQ-5D is an assessment of one's overall health. Consists of 5 items. Patients choose 1 of 3 options that best describe the status of each item. The EQ-5D US based index scores range from -0.11 to 1.0 where a score of 1.0 indicates perfect health. A positive change from baseline indicates health improvement. |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline value. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 101 | 101 |
| Least Squares Mean (Standard Error) [units on a scale] |
0.12
(0.02)
|
0.10
(0.02)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.207 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Model=Treatment, Pooled Investigator, Baseline and Major Depressive Disorder status at baseline. | |
| Title | Number of Participants Discontinuing Due to Adverse Events |
|---|---|
| Description | |
| Time Frame | over 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat Analysis. All randomized patients. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 106 | 109 |
| Number [participants] |
15
14.2%
|
4
3.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Number of Participants With Treatment-Emergent Adverse Events Reported in >5% of Either Treatment Group by Time of Dosing (Morning or Evening) |
|---|---|
| Description | Tolerability of morning versus evening dosing, as assessed by the number of participants with spontaneously reported adverse events. |
| Time Frame | over 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of randomized patients in each treatment arm for each dosing group |
| Arm/Group Title | Duloxetine - Morning Dosing | Duloxetine - Evening Dosing | Placebo - Morning Dosing | Placebo - Evening Dosing |
|---|---|---|---|---|
| Arm/Group Description | 60 mg QD (morning or evening), PO for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | 60 mg QD (morning or evening), PO for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo QD, PO for 12 weeks | Placebo QD, PO for 12 weeks |
| Measure Participants | 53 | 53 | 56 | 53 |
| Abdominal discomfort |
3
2.8%
|
1
0.9%
|
2
0.9%
|
4
NaN
|
| Abdominal distension |
7
6.6%
|
2
1.8%
|
4
1.9%
|
3
NaN
|
| Abdominal pain upper |
0
0%
|
4
3.7%
|
2
0.9%
|
0
NaN
|
| Anorexia |
4
3.8%
|
7
6.4%
|
1
0.5%
|
1
NaN
|
| Arthralgia |
1
0.9%
|
0
0%
|
3
1.4%
|
2
NaN
|
| Asthenia |
2
1.9%
|
4
3.7%
|
0
0%
|
1
NaN
|
| Chest discomfort |
2
1.9%
|
3
2.8%
|
1
0.5%
|
0
NaN
|
| Constipation |
4
3.8%
|
7
6.4%
|
5
2.3%
|
4
NaN
|
| Cough |
2
1.9%
|
0
0%
|
4
1.9%
|
1
NaN
|
| Decreased appetite |
0
0%
|
3
2.8%
|
0
0%
|
1
NaN
|
| Diarrhoea |
4
3.8%
|
6
5.5%
|
5
2.3%
|
1
NaN
|
| Dizziness |
5
4.7%
|
11
10.1%
|
9
4.2%
|
3
NaN
|
| Dry mouth |
2
1.9%
|
4
3.7%
|
1
0.5%
|
2
NaN
|
| Dyslipidaemia |
1
0.9%
|
3
2.8%
|
1
0.5%
|
1
NaN
|
| Dysuria |
5
4.7%
|
4
3.7%
|
0
0%
|
1
NaN
|
| Fatigue |
3
2.8%
|
5
4.6%
|
2
0.9%
|
6
NaN
|
| Headache |
4
3.8%
|
2
1.8%
|
4
1.9%
|
2
NaN
|
| Hyperhidrosis |
4
3.8%
|
5
4.6%
|
1
0.5%
|
2
NaN
|
| Hypersomnia |
0
0%
|
2
1.8%
|
2
0.9%
|
3
NaN
|
| Hypoglycaemia |
5
4.7%
|
5
4.6%
|
3
1.4%
|
2
NaN
|
| Insomnia |
3
2.8%
|
2
1.8%
|
3
1.4%
|
2
NaN
|
| Lethargy |
6
5.7%
|
5
4.6%
|
2
0.9%
|
2
NaN
|
| Nausea |
14
13.2%
|
18
16.5%
|
8
3.7%
|
5
NaN
|
| Pain |
1
0.9%
|
1
0.9%
|
3
1.4%
|
0
NaN
|
| Palpitations |
7
6.6%
|
3
2.8%
|
2
0.9%
|
3
NaN
|
| Pruritus |
2
1.9%
|
1
0.9%
|
4
1.9%
|
4
NaN
|
| Somnolence |
9
8.5%
|
8
7.3%
|
2
0.9%
|
4
NaN
|
| Stomach discomfort |
4
3.8%
|
3
2.8%
|
5
2.3%
|
0
NaN
|
| Therapeutic response unexpected |
6
5.7%
|
3
2.8%
|
6
2.8%
|
6
NaN
|
| Thirst |
4
3.8%
|
1
0.9%
|
0
0%
|
1
NaN
|
| Vomiting |
3
2.8%
|
3
2.8%
|
2
0.9%
|
3
NaN
|
| Title | Change From Baseline to 12 Week Endpoint in Athens Insomnia Scale 8-item and 5-item |
|---|---|
| Description | Estimates sleep difficulty. Consists of 8 items rated on a 4-point scale of 0 (no problem at all) to 3 (very serious problem). Total score of the 8-item version (sum of items 1-8) ranges from 0-24, while total score of the 5-item (sum of items 1-5) ranges from 0-15. |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to Treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline value. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 103 | 109 |
| 5-Item Score |
-2.27
(0.31)
|
-1.97
(0.29)
|
| 8-Item Score |
-3.58
(0.47)
|
-3.31
(0.45)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.364 |
| Comments | P-value for 5-Item Score | |
| Method | ANCOVA | |
| Comments | Model=Treatment, Pooled Investigator, Baseline and Major Depressive Disorder status at baseline. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.590 |
| Comments | P-value for 8-Item Score | |
| Method | ANCOVA | |
| Comments | Model=Treatment, Pooled Investigator, Baseline and Major Depressive Disorder status at baseline. | |
| Title | Vital Signs - Weight |
|---|---|
| Description | Change from baseline to endpoint in body weight. |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of randomized patients with a baseline and at least one non-missing post-baseline value. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 104 | 109 |
| Least Squares Mean (Standard Error) [kilograms] |
-0.17
(0.21)
|
-0.03
(0.21)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.620 |
| Comments | ||
| Method | ANOVA | |
| Comments | Model=Treatment and Pooled Investigator | |
| Title | Vital Signs - Pulse Rate |
|---|---|
| Description | Change from baseline to endpoint in pulse rate. |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of randomized patients with a baseline and at least one non-missing post-baseline value. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 104 | 109 |
| Least Squares Mean (Standard Error) [beats per minute] |
1.71
(1.06)
|
0.32
(1.03)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.324 |
| Comments | ||
| Method | ANOVA | |
| Comments | Model=Treatment and Pooled Investigator | |
| Title | Vital Signs - Blood Pressure |
|---|---|
| Description | Change from baseline to endpoint in systolic and diastolic blood pressure. |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of randomized patients with a baseline and at least one non-missing post-baseline value. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 104 | 109 |
| Systolic Blood Pressure |
-0.48
(1.61)
|
-1.47
(1.56)
|
| Diastolic Blood Pressure |
0.45
(0.95)
|
-0.21
(0.92)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.642 |
| Comments | P-value for Systolic Blood Pressure | |
| Method | ANOVA | |
| Comments | Model=Treatment and Pooled Investigator | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.601 |
| Comments | P-value for Diastolic Blood Pressure | |
| Method | ANOVA | |
| Comments | Model=Treatment and Pooled Investigator | |
| Title | Statistically Significant Change From Baseline to 12 Week Endpoint in Laboratory Measures - Chloride, High Density Lipoprotein, Sodium, and Triglycerides |
|---|---|
| Description | Significantly different laboratory values between the two groups in baseline to endpoint changes in chloride, high density lipoprotein, sodium, and triglycerides. |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of randomized patients with a baseline and at least one non-missing post-baseline value, based on first values at scheduled visits. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 99 | 104 |
| Chloride Baseline |
102.94
(3.07)
|
102.87
(2.99)
|
| Chloride Change to Endpoint |
-1.15
(3.60)
|
-0.20
(2.81)
|
| High Density Lipoprotein Cholesterol Baseline |
1.30
(0.37)
|
1.33
(0.33)
|
| High Density Lipoprotein Change to Endpoint |
0.03
(0.22)
|
-0.04
(0.19)
|
| Sodium Baseline |
143.03
(2.83)
|
142.76
(3.00)
|
| Sodium Change to Endpoint |
-1.25
(3.64)
|
-0.19
(2.72)
|
| Triglycerides Baseline |
1.76
(1.48)
|
1.40
(0.76)
|
| Triglycerides Change to Endpoint |
-0.05
(1.07)
|
0.26
(1.00)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.014 |
| Comments | P-value for Chloride | |
| Method | ANOVA | |
| Comments | Sums of squares from ANOVA on the ranks: Model=Treatment and Pooled Investigator for treatment effects p-value. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | P-value for High Density Lipoprotein Cholesterol | |
| Method | ANOVA | |
| Comments | Sums of squares from ANOVA on the ranks: Model=Treatment and Pooled Investigator for treatment effects p-value. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.011 |
| Comments | P-value for Sodium | |
| Method | ANOVA | |
| Comments | Sums of squares from ANOVA on the ranks: Model=Treatment and Pooled Investigator for treatment effects p-value. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.044 |
| Comments | P-value for triglycerides | |
| Method | ANOVA | |
| Comments | Sums of squares from ANOVA on the ranks: Model=Treatment and Pooled Investigator for treatment effects p-value. | |
| Title | Statistically Significant Change From Baseline to 12 Week Endpoint in Laboratory Measures - Uric Acid |
|---|---|
| Description | Significantly different laboratory values between the two groups in baseline to endpoint changes |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of randomized patients with a baseline and at least one non-missing post-baseline value, based on first values at scheduled visits. |
| Arm/Group Title | Duloxetine | Placebo |
|---|---|---|
| Arm/Group Description | 60 mg every day (QD) (morning or evening), by mouth (PO) for 12 weeks (at week 2, dose can be increased to 120 mg at investigator discretion based on response) | Placebo every day (QD), by mouth (PO) for 12 weeks |
| Measure Participants | 99 | 104 |
| Uric Acid Baseline |
293.24
(72.51)
|
283.98
(75.88)
|
| Uric Acid Change to Endpoint |
-7.46
(62.19)
|
2.49
(53.29)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Duloxetine, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.017 |
| Comments | ||
| Method | ANOVA | |
| Comments | Sums of squares from ANOVA on the ranks: Model=Treatment and Pooled Investigator for treatment effects p-values. | |
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Placebo | Duloxetine 60/120 mg QD | ||
| Arm/Group Description | Placebo | Duloxetine 60/120 mg QD | ||
All Cause Mortality |
||||
| Placebo | Duloxetine 60/120 mg QD | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo | Duloxetine 60/120 mg QD | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/ (NaN) | 2/ (NaN) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 0/109 (0%) | 0 | 1/106 (0.9%) | 1 |
| Cardiac failure acute | 1/109 (0.9%) | 1 | 0/106 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Nausea | 1/109 (0.9%) | 1 | 1/106 (0.9%) | 1 |
| Vomiting | 1/109 (0.9%) | 1 | 1/106 (0.9%) | 1 |
| General disorders | ||||
| Death | 0/109 (0%) | 0 | 1/106 (0.9%) | 1 |
| Infections and infestations | ||||
| Nasopharyngitis | 1/109 (0.9%) | 1 | 0/106 (0%) | 0 |
| Nervous system disorders | ||||
| Cerebral infarction | 0/109 (0%) | 0 | 1/106 (0.9%) | 1 |
| Renal and urinary disorders | ||||
| Renal impairment | 0/109 (0%) | 0 | 1/106 (0.9%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Respiratory failure | 0/109 (0%) | 0 | 1/106 (0.9%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Duloxetine 60/120 mg QD | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 77/ (NaN) | 85/ (NaN) | ||
| Cardiac disorders | ||||
| Palpitations | 5/109 (4.6%) | 6 | 10/106 (9.4%) | 11 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 6/109 (5.5%) | 6 | 4/106 (3.8%) | 4 |
| Abdominal distension | 7/109 (6.4%) | 7 | 9/106 (8.5%) | 9 |
| Constipation | 9/109 (8.3%) | 10 | 12/106 (11.3%) | 14 |
| Diarrhoea | 6/109 (5.5%) | 6 | 11/106 (10.4%) | 11 |
| Dry mouth | 3/109 (2.8%) | 3 | 6/106 (5.7%) | 7 |
| Nausea | 12/109 (11%) | 15 | 31/106 (29.2%) | 33 |
| Stomach discomfort | 5/109 (4.6%) | 6 | 7/106 (6.6%) | 7 |
| General disorders | ||||
| Asthenia | 1/109 (0.9%) | 1 | 6/106 (5.7%) | 6 |
| Fatigue | 8/109 (7.3%) | 8 | 8/106 (7.5%) | 8 |
| Therapeutic response unexpected | 12/109 (11%) | 18 | 9/106 (8.5%) | 15 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 2/109 (1.8%) | 2 | 11/106 (10.4%) | 11 |
| Hypoglycaemia | 6/109 (5.5%) | 7 | 10/106 (9.4%) | 10 |
| Nervous system disorders | ||||
| Dizziness | 12/109 (11%) | 12 | 16/106 (15.1%) | 19 |
| Headache | 6/109 (5.5%) | 8 | 6/106 (5.7%) | 6 |
| Lethargy | 4/109 (3.7%) | 4 | 11/106 (10.4%) | 12 |
| Somnolence | 6/109 (5.5%) | 6 | 17/106 (16%) | 18 |
| Renal and urinary disorders | ||||
| Dysuria | 1/109 (0.9%) | 1 | 9/106 (8.5%) | 9 |
| Skin and subcutaneous tissue disorders | ||||
| Hyperhidrosis | 3/109 (2.8%) | 3 | 9/106 (8.5%) | 11 |
| Pruritus | 8/109 (7.3%) | 8 | 3/106 (2.8%) | 3 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 1-800-545-5979 |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00408993
Other Study ID Numbers:
- 10599
- F1J-MC-HMEQ(a)
First Posted:
Dec 8, 2006
Last Update Posted:
Jul 26, 2011
Last Verified:
Jul 1, 2011