An Open-Label Comparison of Duloxetine to Other Alternatives for the Management of Diabetic Peripheral Neuropathic Pain - Full Text View

Sponsor:	Eli Lilly and Company
Collaborator:	Boehringer Ingelheim Pharmaceuticals
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00385671

Purpose

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.

Condition	Intervention	Phase
Diabetic Neuropathy, Painful	Drug: duloxetine hydrochloride Drug: pregabalin Drug: gabapentin	Phase IV

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

Resource links provided by NLM:

MedlinePlus related topics: Diabetic Nerve Problems

Drug Information available for: Gabapentin Duloxetine Duloxetine hydrochloride Pregabalin

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Mean change from baseline, weekly mean of daily 24 hour average pain score, pregabalin to duloxetine [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mean change from baseline, weekly mean of daily 24-hour average pain score, duloxetine to duloxetine plus gabapentin [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
Mean change from baseline, weekly mean night pain [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
Mean change from baseline, Clinical Global Impression of Severity scale (CGI Severity) [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
Mean change from baseline, Patient's Global Impression of Improvement scale (PGI - Improvement) [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
Mean change in baseline, Brief Pain Inventory (BPI) - severity and interference portions [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
Response rate as defined by ≥ 30% reduction in the weekly mean 24 hour average pain score [ Time Frame: over 12 weeks ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]
Response rate defined by a reduction of ≥ 50% in mean 24 hour average pain score [ Time Frame: over 12 weeks ] [ Designated as 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 ] [ Designated as safety issue: No ]
Summary of Serious Adverse Events and Treatment-emergent adverse events [ Time Frame: over 12 weeks ] [ Designated as safety issue: Yes ]
Summary of Adverse Events and Serious Adverse Events leading to discontinuation [ Time Frame: over 12 weeks ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: Yes ]
Mean change in weekly mean worst pain score [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
Mean change in Beck Depression Inventory II (BDI-II) total score [ Time Frame: over 12 weeks ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]
Summary of Overall discontinuation rates [ Time Frame: over 12 weeks ] [ Designated as safety issue: Yes ]
Time to first ≥ 30% reduction in weekly mean 24 hour average pain score [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
Time to first ≥ 50 % reduction in weekly mean 24 hour average pain score [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
Time to first sustained response (≥ 30% reduction) in weekly mean 24 hour average pain score [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
Time to first ≥ 2 points reduction in weekly mean 24 hour average pain score [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
Weekly mean change in 24 hour average pain severity +/- GAD [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]
Per protocol analysis for weekly mean change from baseline in 24 hour average pain severity [ Time Frame: over 12 weeks ] [ Designated as 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 ] [ Designated as safety issue: No ]
Discontinuations for abnormal laboratory analytes, vital signs, overall and for each measure [ Time Frame: over 12 weeks ] [ Designated as safety issue: Yes ]

Enrollment:	421
Study Start Date:	September 2006
Study Completion Date:	November 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator 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.	Drug: pregabalin
B: Experimental Duloxetine (DLX) 30 mg QD, PO for 2 weeks, then DLX 60 mg QD, PO for 10 weeks;	Drug: duloxetine hydrochloride
C: Experimental Stable Gabapentin (GAB) + Duloxetine (DLX) 30 mg QD, PO for 2 weeks, then stable GAB + DLX 60 mg QD, PO for 10 weeks.	Drug: duloxetine hydrochloride Drug: gabapentin

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00385671

Locations

United States, California
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.
Torrance, California, United States, 90503
United States, Connecticut
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.
Cromwell, Connecticut, United States, 06416
United States, New York
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.
Staten Island, New York, United States, 10312
United States, North Carolina
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.
Greenville, North Carolina, United States, 27834
United States, Utah
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.
Midvale, Utah, United States, 84047
Germany
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.
Bochum, Germany, D-44805
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.
Dresden, Germany, 01307
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.
Hamburg, Germany, 20354
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.
Siegen, Germany, 57072

Sponsors and Collaborators

Eli Lilly and Company

Boehringer Ingelheim Pharmaceuticals

Investigators

Study Director:

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)

Eli Lilly and Company

More Information

Additional Information:

Lilly Clinical Trial Registry This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Eli Lilly ( Chief Medical Officer )
Study ID Numbers:	10822, F1J-US-HMEZ
Study First Received:	October 6, 2006
Last Updated:	December 14, 2009
ClinicalTrials.gov Identifier:	NCT00385671 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Gabapentin
Anti-Dyskinesia Agents
Physiological Effects of Drugs
Psychotropic Drugs
Antiparkinson Agents
Calcium Channel Blockers
Excitatory Amino Acid Agents
Duloxetine
Membrane Transport Modulators

Neuromuscular Diseases
Sensory System Agents
Therapeutic Uses
Analgesics
Antidepressive Agents
Diabetes Complications
Excitatory Amino Acid Antagonists
Tranquilizing Agents
Diabetic Neuropathies
Nervous System Diseases
Diabetes Mellitus
Central Nervous System Depressants
Pregabalin
Endocrine System Diseases
Cardiovascular Agents

ClinicalTrials.gov processed this record on February 08, 2010