A Study of Duloxetine (LY248686) in Participants With Diabetic Peripheral Neuropathic Pain (DPNP)

NCT02417935 | Completed Phase 4 Results

• 2 other identifiers: 14378F1J-JE-HMHA
• Study Type: interventional
• Target: 304
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Diabetic Peripheral Neuropathic Pain

Outcome Measures

Primary Outcomes (1)

• 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)

  11-point NRS measures the severity of pain over the previous 24 hours. Participants were asked to provide 24-hour average pain scores in the daily Participant diary and among these, the weekly mean of the 24-hour average pain score was calculated. Scores range from 0 (no pain) to 10 (pain as bad as you can imagine). Mixed Model Repeated Measures (MMRM) model with baseline value, Duration of diabetic peripheral neuropathic pain (DPNP), treatment, week, treatment-by-week interaction as fixed effects was used to produce Least Square Mean (LS Mean).

  Baseline, Week 12

Secondary Outcomes (9)

• Patient Global Impression of Improvement (PGI-I) at 12 Weeks

  Week 12

• Change From Baseline to 12 Weeks on the Brief Pain Inventory-Severity and Interference Rating Short Form (BPI-SF)

  Baseline, Week 12

• Change From Baseline to 12 Weeks on the Neuropathic Pain Symptom Inventory (NPSI)

  Baseline, Week 12

• Clinical Global Impression of Improvement (CGI-I) at 12 Weeks

  Week 12

• Change From Baseline to 12 Weeks on the EuroQol 5 Dimension (EQ-5D)

  Baseline, Week 12

Study Arms (2)

Duloxetine

EXPERIMENTAL

20 milligrams (mg) duloxetine orally once a day (QD) for one week and then 40 mg duloxetine orally QD for 3 weeks. Duloxetine dosage may be increased up to 60 mg QD at week 4 or week 8. Placebo will be given with duloxetine for blinding. Dosage will be tapered down during the final week of the study.

Drug: Duloxetine; Drug: Placebo

Pregabalin

ACTIVE COMPARATOR

150 mg pregabalin orally twice a day (BID) for 1 week and then 300 mg pregabalin orally BID for 3 weeks. Pregabalin dosage may be increased up to 450 mg BID at week 4 or 8, and increased up to 600 mg BID at week 8. Placebo will be given with pregabalin for blinding. Dosage will be tapered down during the final week of the study.

Drug: Pregabalin; Drug: Placebo

Interventions

Duloxetine DRUG

Administered orally

Also known as: LY248686

Duloxetine

Pregabalin DRUG

Administered orally

Pregabalin

Placebo DRUG

Administered orally

Duloxetine; Pregabalin

Eligibility Criteria

• Age: 20 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Shionogi: collaborator

Related Publications (1)

• 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.

  PMID: 30271191 DERIVED

MeSH Terms

Interventions

Duloxetine Hydrochloride; Pregabalin

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2015
• First Posted: April 16, 2015
• Study Start: April 1, 2015
• Primary Completion: May 13, 2017
• Study Completion: May 13, 2017
• Last Updated: September 18, 2019
• Results First Posted: July 10, 2018

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.