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”

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.

Intervention(s) in this Clinical Trial

• Drug: duloxetine hydrochloride
  • Duloxetine (DLX) once daily (QD), orally (PO)
• Drug: pregabalin
  • Pregabalin (PGB) orally (PO)
• Drug: gabapentin
  • Stable Gabapentin (GAB) (participants will remain on the same dose of gabapentin at which they entered the study)

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Pregabalin
  • Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US & Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US & Germany) or 150 mg BID (Canada), PO for 10 weeks.
• Experimental: Duloxetine
  • Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.
• Experimental: Gabapentin + Duloxetine
  • Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.

Primary Measures

• Mean Change From Baseline to 12 Weeks in Weekly Mean of Daily 24 Hour Average Pain Score, Pregabalin Compared With Duloxetine
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No

Secondary Measures

• Mean Change From Baseline to 12 Weeks in Weekly Mean of Daily 24 Hour Average Pain Score, Duloxetine Compared With Duloxetine+Gabapentin
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Weekly Mean of Nighttime Pain Severity
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Weekly Mean of the Daily Worst Pain Severity Score
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Clinical Global Impression of Severity Scale (CGI Severity)
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Patient's Global Impression of Improvement Scale (PGI - Improvement) at 12 Weeks
  • Time Frame: 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: 24-hour Average Pain
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Worst Pain
  • Time Frame: baseline, 12 Weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Least Pain
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Pain Right Now
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference: With General Activity
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Mood
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Walking Ability
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Normal Work
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Relations With Other People
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Sleep
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Enjoyment of Life
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Mean Interference Score
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Number of Participants With ≥ 30% Reduction in the Weekly Mean 24 Hour Average Pain Score at 12 Weeks
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Number of Patients With a Reduction of ≥ 50% in Weekly Mean of 24 Hour Average Pain Score
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Number of Participants With a ≥ 2-points Reduction on the Weekly Average of the Daily 24-hour Average Pain Scale at 12 Weeks
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• 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)
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Sheehan Disability Scale (SDS) - Total Score and Scores for Items 1 to 3
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation
  • Time Frame: baseline through 12 weeks
    Safety Issue?: Yes
• Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores
  • Time Frame: baseline, 12 weeks
    Safety Issue?: Yes
• Categorial Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores
  • Time Frame: baseline, 12 weeks
    Safety Issue?: Yes
• Path Analysis of Improvement in Pain Through Improvement in Depressive Symptoms
  • Time Frame: baseline through 12 weeks
    Safety Issue?: No
• Mean Change From Baseline to 12 Weeks in Beck Depression Inventory II (BDI-II) Total Score
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Summary of Number of Participants Who Discontinued
  • Time Frame: baseline through 12 weeks
    Safety Issue?: Yes
• Time to First ≥ 30% Reduction in Weekly Mean 24 Hour Average Pain Score
  • Time Frame: baseline through 12 weeks
    Safety Issue?: No
• Time to First ≥ 50 % Reduction in Weekly Mean 24 Hour Average Pain Score
  • Time Frame: baseline through 12 weeks
    Safety Issue?: No
• Time to First Sustained Response in Weekly Mean 24 Hour Average Pain Score
  • Time Frame: baseline through 12 weeks
    Safety Issue?: No
• Time to First ≥ 2 Points Reduction in Weekly Mean 24 Hour Average Pain Score
  • Time Frame: baseline through 12 weeks
    Safety Issue?: No
• Weekly Mean Change in 24 Hour Average Pain Severity +/- Generalized Anxiety Disorder (GAD)
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• 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)
  • Time Frame: baseline, 12 weeks
    Safety Issue?: No
• Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use)
  • Time Frame: 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
    Safety Issue?: No
• Discontinuations for Abnormal Laboratory Analytes, Vital Signs, Overall and for Each Measure
  • Time Frame: baseline through 12 weeks
    Safety Issue?: Yes
• Mean Change From Baseline to 12 Weeks in Blood Pressure
  • Time Frame: baseline through 12 weeks
    Safety Issue?: Yes
• Mean Change From Baseline to 12 Weeks in Heart Rate
  • Time Frame: baseline through 12 weeks
    Safety Issue?: Yes
• Mean Change From Baseline to 12 Weeks in Body Weight
  • Time Frame: baseline through 12 weeks
    Safety Issue?: Yes
• Number of Participants With Treatment-emergent Elevated Blood Pressure
  • Time Frame: baseline through 12 weeks
    Safety Issue?: Yes
• Number of Participants With Treatment-Emergent Elevated Heart Rate
  • Time Frame: baseline through 12 weeks
    Safety Issue?: Yes
• Number of Participants With Treatment-Emergent Changes in Body Weight
  • Time Frame: baseline through 12 weeks
    Safety Issue?: Yes
• Mean Change From Baseline to 12 Weeks in Hepatic Enzyme Serum Levels
  • Time Frame: baseline, 12 weeks
    Safety Issue?: Yes
• Mean Change From Baseline to 12 Weeks in Total Bilirubin
  • Time Frame: baseline, 12 weeks
    Safety Issue?: Yes
• Mean Change From Baseline to 12 Weeks in Fasting Plasma Glucose
  • Time Frame: baseline, 12 weeks
    Safety Issue?: Yes
• Mean Change From Baseline to 12 Weeks in Hemoglobin A1C
  • Time Frame: baseline, 12 weeks
    Safety Issue?: Yes
• Number of Patients With Treatment-Emergent Elevated Laboratory Analytes
  • Time Frame: baseline through 12 weeks
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Eli Lilly and Company Industry

Overall Clinical Trial Officials and Contacts

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) Study Director Eli Lilly and Company  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00385671

Study ID Number: 10822

ClinicalTrials.gov Identifier: NCT00385671

Health Authority: United States: Food and Drug Administration

Lilly Clinical Trial Registry