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.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2009

Intervention(s) in this Clinical Trial

• Drug: duloxetine hydrochloride
• Drug: pregabalin
• Drug: gabapentin

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: A
  • Pregabalin (PGB) 50 mg TID(US & Germany), 75 mg BID (Canada)PO for 2 weeks, then PGB 100 mg TID (US & Germany); 150 mg BID (Canada), PO for 10 weeks.
• Experimental: B
  • Duloxetine (DLX) 30 mg QD, PO for 2 weeks, then DLX 60 mg QD, PO for 10 weeks;
• Experimental: C
  • Stable Gabapentin (GAB) + Duloxetine (DLX) 30 mg QD, PO for 2 weeks, then stable GAB + DLX 60 mg QD, PO for 10 weeks.

Primary Measures

• Mean change from baseline, weekly mean of daily 24 hour average pain score, pregabalin to duloxetine
  • Time Frame: over 12 weeks
    Safety Issue?: No

Secondary Measures

• Mean change from baseline, weekly mean of daily 24-hour average pain score, duloxetine to duloxetine plus gabapentin
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Mean change from baseline, weekly mean night pain
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Mean change from baseline, Clinical Global Impression of Severity scale (CGI Severity)
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Mean change from baseline, Patient's Global Impression of Improvement scale (PGI - Improvement)
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Mean change in baseline, Brief Pain Inventory (BPI) - severity and interference portions
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Response rate as defined by ≥ 30% reduction in the weekly mean 24 hour average pain score
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Mean change from baseline, Leeds Sleep Evaluation Questionnaire subscales of ease of going to sleep (GTS), awakening (AFS), and behaviour following wakefulness (BFW), quality of sleep (QOS)
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Mean change from baseline, Sheehan Disability Scale (SDS)- total score and items work, family, social, days lost, days underproductive
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Response rate defined by a reduction of ≥ 50% in mean 24 hour average pain score
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Response rate as defined by a ≥ 2-points reduction on the weekly average of the daily 24-hour average pain scale
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Summary of Serious Adverse Events and Treatment-emergent adverse events
  • Time Frame: over 12 weeks
    Safety Issue?: Yes
• Summary of Adverse Events and Serious Adverse Events leading to discontinuation
  • Time Frame: over 12 weeks
    Safety Issue?: Yes
• Changes in vital signs and weight including baseline to endpoint abnormal values at any time, and abnormal values at endpoint
  • Time Frame: over 12 weeks
    Safety Issue?: Yes
• Change in laboratory values, including baseline to endpoint, abnormal values at any time and abnormal values at endpoint
  • Time Frame: over 12 weeks
    Safety Issue?: Yes
• Mean change in change in Sexual Functioning Questionnaire (CSFQ)total score and subscale scores, categorical change based on total score and subscales (better, same, worse)
  • Time Frame: Over 12 weeks
    Safety Issue?: No
• Mean change in Portland Neurotoxicity Scale total score, cognitive and somatomotor subscales, categorical change from baseline in total and subscales (better, same, worse)
  • Time Frame: over 12 weeks
    Safety Issue?: Yes
• Mean change in weekly mean worst pain score
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Mean change in Beck Depression Inventory II (BDI-II) total score
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Relative contribution of mood states on weekly mean change in 24 hour average pain severity as measured by the Beck Depression Inventory II(BDI-II)total score path analysis
  • Time Frame: over 12 weeks
    Safety Issue?: Yes
• Change in percent of patients using health care as measured by the resource utilization scale, individual items 2, 4, 9-17, 19, 23 will be compared with baseline, categorical analysis for equal, lower or greater utilization
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Summary of Overall discontinuation rates
  • Time Frame: over 12 weeks
    Safety Issue?: Yes
• Time to first ≥ 30% reduction in weekly mean 24 hour average pain score
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Time to first ≥ 50 % reduction in weekly mean 24 hour average pain score
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Time to first sustained response (≥ 30% reduction) in weekly mean 24 hour average pain score
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Time to first ≥ 30% reduction in weekly mean 24 hour average pain score
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Time to first ≥ 2 points reduction in weekly mean 24 hour average pain score
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Weekly mean change in 24 hour average pain severity +/- GAD
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Per protocol analysis for weekly mean change from baseline in 24 hour average pain severity
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Weekly mean change in 24 hour average pain severity by week by gabapentin exposure subgroup (de novo vs. prior use)
  • Time Frame: over 12 weeks
    Safety Issue?: No
• Discontinuations for abnormal laboratory analytes, vital signs, overall and for each measure
  • Time Frame: over 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 mg/d, 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 Sponsor: Eli Lilly and Company

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  

Overall Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 

Information obtained from ClinicalTrials.gov on January 08, 2009

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