Clinical trial NCT02417935: A Study of Duloxetine (LY248686) in Participants With Diabetic Peripheral Neuropathic Pain (DPNP)
Official title: A Japan Post-Marketing, Randomized, Double-Blind, Parallel-Group, Flexible Dose Comparative Study to Assess the Non-Inferiority of Duloxetine Compared With Pregabalin in Patients With Diabetic Peripheral Neuropathic Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Peripheral Neuropathic Pain
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Shionogi
First posted: 2015-04-16
Enrollment: 304
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the effectiveness and safety of the study drug known as duloxetine in participants with diabetic peripheral neuropathic pain.


Eligibility criteria: Inclusion Criteria:

* Participants present with pain due to bilateral, peripheral neuropathy
* Participants who have hemoglobin A1c (HbA1c) ≤9.4% (National Glycohemoglobin Standardization Program \[NGSP\]) at screening
* Participants who have HbA1c that has been measured 42 to 70 days prior to screening, and the range of variation in the values measured, thereafter, is within ±1.0% of the value measured at screening
* Participants who have a score of at least 4 on the mean of the 24-hour average pain score measured using 11-point NRS (Numeric Rating Scale) in the daily diary (should be calculated from records 7 days immediately prior to randomization)
* Participants who have made complete daily diary entries 80% or more of the time from screening to randomization

Exclusion Criteria:

* Participants who have undergone renal transplant, or are currently undergoing renal dialysis
* Participants who have uncontrolled narrow-angle glaucoma, history of uncontrolled seizures, or uncontrolled or poorly controlled hypertension
* Participants whose glycemic control has been poor within 70 days immediately prior to screening (for example, ketoacidosis requiring hospitalization, or hypoglycemia that may cause consciousness disorder)
* Pregnant or lactating female participants, or male participants who are planning for their partners to be or become pregnant during the timeframe of the study
* Participants who have hypersensitivity to multiple medications
* Participants who answered "yes" to either question 4 (active suicidal ideation with some intent to act, without specific plan) or question 5 (active suicidal ideation with specific plan and intent) on the "suicidal ideation" portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) or answered "yes" to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act or behavior) on the "suicidal behavior" portion of the C-SSRS; and the ideation or behavior occurred within the past month
* Participants who have past history of psychiatric diseases, such as depression, anxiety disorder, eating disorder, etc., that required drug therapy in the past 1 year, or who are currently having complications of these diseases or any history of manic psychosis or bipolar disorder
* Participants who have major depressive disorder as determined using the depression module of the Mini-International Neuropsychiatric Interview (MINI)
* Participants who have complications of diseases that are considered to affect the assessment of diabetic peripheral neuropathic pain. For example, nerve diseases with pain other than diabetic peripheral neuropathic pain (cervical spondylosis, carpal tunnel syndrome, spinal canal stenosis, and post-herpetic pain), pain diseases other than nerve diseases (collagen diseases, gout, chronic obstructive arteriosclerosis, and arthritis), and other pain at the site of evaluation (skin diseases and traumatic injury) are excluded
* Participants who have neuropathic pain suspected to be caused by alcohol
* Participants who have been treated with a monoamine oxidase (MAO) inhibitor(s) within 14 days immediately prior to randomization. Participants who visited the investigator site 14 days prior to randomization, those who have been treated with MAO inhibitors(s), thereafter, are excluded
* Participants who have alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at a level ≥100 units/liter at screening
* Participants who have total bilirubin at a level ≥1.5 milligrams/deciliter (mg/dL) at screening
* Participants who have creatinine clearance (CrCL), calculated by Cockcroft-Gault, that is \<1.0 milliliters/second (mL/s) (\<60 mL/minute) at screening
* Participants who have a white blood cell (WBC) value \<2500/cubic millimeters (mm3), neutrophils \<1500/mm3, or platelets \<100×103/mm3 on their hematology tests at screening
* Participants who are introduced to any treatments for diabetes, or a change in dosing regimen of any treatments for diabetes (exclude insulin treatment), or resumption of insulin treatment after screening
* Participants who have been treated with prohibited concomitant drug(s), or who have undergone prohibited concomitant treatment(s) after screening
* Participants who have taken restricted concomitant drugs 27 days immediately before screening, with continued use of the restricted concomitant drug prior to screening
* Participants who have taken acetaminophen for 4 days or more 7 days immediately prior to randomization

Primary outcomes:
measure: Change From Baseline to 12 Weeks in the Weekly Mean of the 24-Hour Average Pain Score on the 11-Point Numeric Rating Scale (NRS)
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Patient Global Impression of Improvement (PGI-I) at 12 Weeks
timeFrame: Week 12
measure: Change From Baseline to 12 Weeks on the Brief Pain Inventory-Severity and Interference Rating Short Form (BPI-SF)
timeFrame: Baseline, Week 12
measure: Change From Baseline to 12 Weeks on the Neuropathic Pain Symptom Inventory (NPSI)
timeFrame: Baseline, Week 12
measure: Clinical Global Impression of Improvement (CGI-I) at 12 Weeks
timeFrame: Week 12
measure: Change From Baseline to 12 Weeks on the EuroQol 5 Dimension (EQ-5D)
timeFrame: Baseline, Week 12
measure: Change From Baseline to 12 Weeks on the Beck Depression Inventory-II (BDI-II) Total Score
timeFrame: Baseline, Week 12
measure: Change From Baseline to 12 Weeks in the Weekly Mean of Night Pain Scores on the 11-Point NRS
timeFrame: Baseline, Week 12
measure: Change From Baseline to 12 Weeks in the Weekly Mean of the 24-Hour Worst Pain Scores on the 11-Point NRS
timeFrame: Baseline, Week 12
measure: Number of Participants With a 30% and 50% Reduction in the Weekly Mean of the 24-Hour Average Pain Score on the 11-Point NRS at 12 Weeks
timeFrame: Week 12
Other outcomes:
Locations:
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: Enomoto H, Yasuda H, Nishiyori A, Fujikoshi S, Furukawa M, Ishida M, Takahashi M, Tsuji T, Yoshikawa A, Alev L. Duloxetine in patients with diabetic peripheral neuropathic pain in Japan: a randomized, doubleblind, noninferiority comparative study with pregabalin. J Pain Res. 2018 Sep 13;11:1857-1868. doi: 10.2147/JPR.S170646. eCollection 2018.