Clinical trial NCT00385671: An Open-Label Comparison of Duloxetine to Other Alternatives for the Management of Diabetic Peripheral Neuropathic Pain
Official title: An Open-Label, Randomized Comparison of Duloxetine, Pregabalin, and the Combination of Duloxetine and Gabapentin Among Patients With Inadequate Response to Gabapentin for the Management of Diabetic Peripheral Neuropathic Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Neuropathy, Painful
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Boehringer Ingelheim
First posted: 2006-10-11
Enrollment: 407
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To test the non-inferiority of duloxetine monotherapy as a treatment for the management of diabetic peripheral neuropathic pain as compared to pregabalin treatment among patients who have not had an adequate response to gabapentin.


Eligibility criteria: Inclusion Criteria:

* You must have been diagnosed with Diabetic Neuropathic Pain
* Patient has an average daily pain score greater than or equal to 4 on an 11-point Likert scale, and patient or provider feel that a change from the current gabapentin therapy for pain management is warranted
* Patient is currently treated with gabapentin greater than or equal to 900 milligram/day, has been prescribed the current dose for at least 4 weeks, and has been at least 80% compliant with dosing, according to patient report
* Patient must agree not to change dose of gabapentin between Visits 1 and 2
* You must have stable glycemic control

Exclusion Criteria:

* Are judged prior to randomization to be at suicidal risk as defined by a score of 2 or greater on question 9 of the Beck Depression Inventory-II (BDI-II)
* Current diagnosis or history of hemangiosarcoma
* Patients with New York Heart Association Class III or IV symptoms of congestive heart failure
* Patients with uncontrolled narrow-angle glaucoma
* Presence of a current seizure disorder

Primary outcomes:
measure: Mean Change From Baseline to 12 Weeks in Weekly Mean of Daily 24 Hour Average Pain Score, Pregabalin Compared With Duloxetine
timeFrame: baseline, 12 weeks
Secondary outcomes:
measure: Mean Change From Baseline to 12 Weeks in Weekly Mean of Daily 24 Hour Average Pain Score, Duloxetine Compared With Duloxetine+Gabapentin
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Weekly Mean of Nighttime Pain Severity
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Weekly Mean of the Daily Worst Pain Severity Score
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Clinical Global Impression of Severity Scale (CGI Severity)
timeFrame: baseline, 12 weeks
measure: Patient's Global Impression of Improvement Scale (PGI - Improvement) at 12 Weeks
timeFrame: 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: 24-hour Average Pain
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Worst Pain
timeFrame: baseline, 12 Weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Least Pain
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Pain Right Now
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference: With General Activity
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Mood
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Walking Ability
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Normal Work
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Relations With Other People
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Sleep
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Enjoyment of Life
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Mean Interference Score
timeFrame: baseline, 12 weeks
measure: Number of Participants With ≥ 30% Reduction in the Weekly Mean 24 Hour Average Pain Score at 12 Weeks
timeFrame: baseline, 12 weeks
measure: Number of Patients With a Reduction of ≥ 50% in Weekly Mean of 24 Hour Average Pain Score
timeFrame: baseline, 12 weeks
measure: Number of Participants With a ≥ 2-points Reduction on the Weekly Average of the Daily 24-hour Average Pain Scale at 12 Weeks
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Leeds Sleep Evaluation Questionnaire (LSEQ) Subscales of Ease of Going to Sleep (GTS), Awakening (AFS), and Behavior Following Wakefulness (BFW), Quality of Sleep (QOS)
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Sheehan Disability Scale (SDS) - Total Score and Scores for Items 1 to 3
timeFrame: baseline, 12 weeks
measure: Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation
timeFrame: baseline through 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores
timeFrame: baseline, 12 weeks
measure: Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores
timeFrame: baseline, 12 weeks
measure: Categorial Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores
timeFrame: baseline, 12 weeks
measure: Path Analysis of Improvement in Pain Through Improvement in Depressive Symptoms
timeFrame: baseline through 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Beck Depression Inventory II (BDI-II) Total Score
timeFrame: baseline, 12 weeks
measure: Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale
timeFrame: baseline, 12 weeks
measure: Summary of Number of Participants Who Discontinued
timeFrame: baseline through 12 weeks
measure: Time to First ≥ 30% Reduction in Weekly Mean 24 Hour Average Pain Score
timeFrame: baseline through 12 weeks
measure: Time to First ≥ 50 % Reduction in Weekly Mean 24 Hour Average Pain Score
timeFrame: baseline through 12 weeks
measure: Time to First Sustained Response in Weekly Mean 24 Hour Average Pain Score
timeFrame: baseline through 12 weeks
measure: Time to First ≥ 2 Points Reduction in Weekly Mean 24 Hour Average Pain Score
timeFrame: baseline through 12 weeks
measure: Weekly Mean Change in 24 Hour Average Pain Severity +/- Generalized Anxiety Disorder (GAD)
timeFrame: baseline, 12 weeks
measure: Weekly Mean Change From Baseline to 12 Weeks in 24 Hour Average Pain Severity - Only Participants Who Adhered to Key Protocol Requirements (Per-Protocol Population)
timeFrame: baseline, 12 weeks
measure: Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use)
timeFrame: baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks
measure: Discontinuations for Abnormal Laboratory Analytes, Vital Signs, Overall and for Each Measure
timeFrame: baseline through 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Blood Pressure
timeFrame: baseline through 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Heart Rate
timeFrame: baseline through 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Body Weight
timeFrame: baseline through 12 weeks
measure: Number of Participants With Treatment-emergent Elevated Blood Pressure
timeFrame: baseline through 12 weeks
measure: Number of Participants With Treatment-Emergent Elevated Heart Rate
timeFrame: baseline through 12 weeks
measure: Number of Participants With Treatment-Emergent Changes in Body Weight
timeFrame: baseline through 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Hepatic Enzyme Serum Levels
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Total Bilirubin
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Fasting Plasma Glucose
timeFrame: baseline, 12 weeks
measure: Mean Change From Baseline to 12 Weeks in Hemoglobin A1C
timeFrame: baseline, 12 weeks
measure: Number of Patients With Treatment-Emergent Elevated Laboratory Analytes
timeFrame: baseline through 12 weeks
Other outcomes:
Locations:
city: Torrance
country: United States
facility: 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.
state: California
city: Cromwell
country: United States
facility: 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.
state: Connecticut
city: Staten Island
country: United States
facility: 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.
state: New York
city: Greenville
country: United States
facility: 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.
state: North Carolina
city: Midvale
country: United States
facility: 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.
state: Utah
city: Bochum
country: Germany
facility: 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.
city: Dresden
country: Germany
facility: 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.
city: Hamburg
country: Germany
facility: 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.
city: Siegen
country: Germany
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Tanenberg RJ, Irving GA, Risser RC, Ahl J, Robinson MJ, Skljarevski V, Malcolm SK. Duloxetine, pregabalin, and duloxetine plus gabapentin for diabetic peripheral neuropathic pain management in patients with inadequate pain response to gabapentin: an open-label, randomized, noninferiority comparison. Mayo Clin Proc. 2011 Jul;86(7):615-26. doi: 10.4065/mcp.2010.0681.
citation: Irving G, Tanenberg RJ, Raskin J, Risser RC, Malcolm S. Comparative safety and tolerability of duloxetine vs. pregabalin vs. duloxetine plus gabapentin in patients with diabetic peripheral neuropathic pain. Int J Clin Pract. 2014 Sep;68(9):1130-40. doi: 10.1111/ijcp.12452. Epub 2014 May 18.