Clinical Trials/NCT00785577

NCT00785577

Completed

Phase 2

A Phase 2 Study of the Effects of LY545694, an iGluR5 Antagonist, in the Treatment of Subjects With Painful Diabetic Neuropathy.

Eli Lilly and Company1 site in 1 country273 target enrollmentNovember 2008

ConditionsDiabetic Neuropathy, Painful

InterventionsPlacebo Pregabalin LY545694 21 mg LY545694 49 mg LY545694 105 mg

DrugsPlacebo Pregabalin LY545694 21 mg LY545694 49 mg LY545694 105 mg

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: Diabetic Neuropathy, Painful
Sponsor: Eli Lilly and Company
Enrollment: 273
Locations: 1
Primary Endpoint: Change From Baseline in Weekly Mean 24-hour Average Pain Severity (APS) Score at 5 Weeks
Status: Completed
Last Updated: 13 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to test whether a new treatment will be safe and effective in treating pain. Patients with diabetic peripheral neuropathy will be included.

Registry

clinicaltrials.gov

Start Date

November 2008

End Date

June 2010

Last Updated

13 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Eli Lilly and Company

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Have pain due to peripheral neuropathy based on disease diagnostic criteria: must have Type 1 or Type 2 diabetes mellitus, pain must being in the feet, with relatively symmetrical onset, daily pain must be present for at least 6 months, and diagnosis must be confirmed by a score of at least 3 on Part B of the Michigan Neuropathy Screening Instrument.
•Have stable glycemic control, and glycated hemoglobin (HbA1c) less than or equal to 10%
•Mean score of at least 4 on the 24-hour average page severity assessment from (from daily diary) Visits 2 to
•Fully completed daily diaries for at least 70% of the days between Visit 2 and
•Women must test negative for a serum pregnancy test at Visit 1, and must agree to use medically acceptable and reliable means of birth control as determined by the investigator during the study and for 1 month following the last dose of study drug.
•Are competent and able to freely give own informed consent.
•Have an educational level and degree of understanding such that they can communicate intelligible with the investigator and study coordinator.
•Have been judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol.

Exclusion Criteria

•Have historical exposure to drugs known to cause neuropathy, or a history of a medical condition, including pernicious anemia and hypothyroidism, that could have been responsible for neuropathy.
•Have pain that cannot be clearly differentiated from or conditions that interfere with the assessment of diabetic neuropathy pain.
•Have had treatment with any centrally active neuroleptic drug within 30 days of visit
•Have had intolerance to pregabalin or have frequent and/or severe allergic reactions with multiple medications.
•Have current or previous (within the past 1 year) Axis 1 diagnosis of major depressive disorder, mania, bipolar disorder, psychosis, dysthymia, generalized anxiety disorder, alcohol or eating disorders according to Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria, as determined by the investigator and confirmed by the Mini-International Neuropsychiatric Interview (MINI).
•Have a serious of unstable cardiovascular, hepatic, renal, respiratory, ophthalmologic, gastrointestinal, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition that in the opinion of the investigator would compromise participation or be likely to lead to hospitalization during the course of the study.
•Have alanine aminotransaminase \> 2 times upper limit of normal at Visit 1, based on reference ranges of central lab.
•Have prior renal transplant, current renal dialysis, or serum creatinine laboratory values \> 1.5 times upper limit of normal, based on reference ranges of the central lab at Visit
•Have a diagnosis or history of glaucoma.
•Are taking excluded medication that cannot be stopped and washed out prior to Visit

Arms & Interventions

Placebo

LY545694 placebo twice daily (BID) oral (po) for 5 weeks and pregabalin placebo capsules thrice daily (TID) po for 6 weeks

Intervention: Placebo

Pregabalin

Pregabalin thrice daily (TID) oral for 6 weeks: 50 mg TID po for Week 1, 100 mg TID po for Weeks 2 - 5, and 50 mg TID po taper for Week 6 LY545694 placebo BID po for 5 weeks

Intervention: Pregabalin

LY545694 21 mg

LY545694 21 milligrams (mg) BID po for 1 week Pregabalin placebo TID po for 6 weeks

Intervention: LY545694 21 mg

LY545694 49 mg

LY545694 escalated to 49 mg BID po during Week 2; possible titration down to 21 mg BID po within 1 week of escalation for remainder of study treatment. Pregabalin placebo TID po for 6 weeks

Intervention: LY545694 49 mg

LY545694 105 mg

LY545694 escalated to 105 mg BID po during Week 3 through Week 5; possible titration down to 49 mg BID po within 1 week of escalation for the remainder of study treatment. Pregabalin placebo TID po for 6 weeks

Intervention: LY545694 105 mg

Outcomes

Primary Outcomes

Change From Baseline in Weekly Mean 24-hour Average Pain Severity (APS) Score at 5 Weeks

Time Frame: Baseline, 5 weeks

This scale measured 24-hour APS scores. Data were recorded daily (preferably at bedtime) on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). Least Squares (LS) Means were adjusted for baseline, investigator, treatment, visit, a treatment-by-visit interaction, and a baseline-by-visit interaction.

Secondary Outcomes

Change From Baseline in Short Form-36 (SF-36) Health Survey Bodily Pain Score at 5 Weeks(Baseline, 5 weeks)
Change From Baseline in Brief Pain Inventory - Severity (BPI-S) Subscale Score at 5 Weeks(Baseline, 5 weeks)
Change From Baseline of European Quality of Life Scale - 5 Dimensions (EQ-5D) at 5 Weeks: United States Population Based Index Score(Baseline, 5 weeks)
Number of Participants Who Discontinued Due to Adverse Events (AEs) During the Therapy (Double-blind) Phase and 1-Week Washout (Follow-up) Phase(Baseline through 6 weeks)
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at 5 Weeks(Baseline, 5 weeks)
Change From Baseline in Weekly Mean Worst Daily Pain Severity Score at 5 Weeks(Baseline, 5 weeks)
Number of Participants With 30% Reduction in Weekly Mean 24-hour Average Pain Severity (APS) Score(Baseline through 5 weeks)
Patient Global Impression of Improvement (PGI-I) Score at 5 Weeks(Week 5)
Change From Baseline in Short-form McGill Pain Questionnaire (SF-MPQ) Sensory Subscale Score at 5 Weeks(Baseline, 5 weeks)
Change From Baseline in Neuropathy-Specific Quality of Life (NeuroQoL) Questionnaire Score at 5 Weeks(Baseline, 5 weeks)
Change From Baseline in Sheehan Disability Scale (SDS) Global Impairment Score at 5 Weeks(Baseline, 5 weeks)
Number of Participants With Serious Treatment Emergent Abnormal High or Low Laboratory Values(Baseline through 5 weeks)
Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure at 5 Weeks(Baseline, 5 weeks)
Change From Baseline in Weekly Mean Night Pain Severity Score at 5 Weeks(Baseline, 5 weeks)
Change From Baseline in Average Brief Pain Inventory - Interference (BPI-I) Subscale Score at 5 Weeks(Baseline, 5 weeks)
Change From Baseline in Assessment of Sleep Questionnaire (ASQ) Total Score at 5 Weeks(Baseline, 5 weeks)
Time to Response(Baseline through 5 weeks)
Change From Baseline in Overall Total Quick Inventory of Depressive Symptomatology (QIDS) Score(Baseline, 5 weeks)
Number of Participants Reporting Blurry or Hazy Vision Using the Subjective Vision Inventory (SVI) Question 1 (Q1) at 5 Weeks(Week 5)
Change From Baseline in Vital Signs: Pulse Rate at 5 Weeks(Baseline, 5 weeks)
Number of Participants With Electrocardiogram Change in Heart Rate Using Bazett's (QTcB) and Fridericia's (QTcF) Formulas(Baseline through 5 weeks)
Percentage of Participants With Reported Hypoglycemic Events(Baseline through 5 weeks)
Pharmacokinetic (PK) Parameter: Clearance of LY545694 (CLp) and Compound 645838 (CLm)(Baseline through 5 weeks)
Number of Participants With Suicidal Behaviors and Ideations(Baseline through week 5)
Number of Participants With Neurological Treatment Emergent Adverse Events (TEAEs)(Baseline through 5 weeks)