Clinical trial NCT00785577: A Study for Treatment of Pain in Patients With Diabetic Neuropathy.
Official title: A Phase 2 Study of the Effects of LY545694, an iGluR5 Antagonist, in the Treatment of Subjects With Painful Diabetic Neuropathy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Neuropathy, Painful
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-11-05
Enrollment: 273
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 3.
* Fully completed daily diaries for at least 70% of the days between Visit 2 and 3.
* 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 3.
* 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 1.
* Have a diagnosis or history of glaucoma.
* Are taking excluded medication that cannot be stopped and washed out prior to Visit 2.
* Have history of substance abuse or dependence within the past year, excluding nicotine and caffeine.
* Are judged clinically by the investigator to be at suicidal risk in the opinion of the investigator based upon clinical interview and the Columbia Suicide-Severity Rating Scale.
* Have a positive urine drug screen for any substance of abuse or excluded medication.
* Are unwilling or unable to comply with the use of a data collection device to directly record data from the subject (daily diary).
* Are pregnant or breast-feeding.
* Are investigator site personnel directly affiliated with this study and/or their immediate families.
* Are Lilly employees.
* Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
* Have a history of recurrent seizures other than febrile seizures.
* Have a history of severe gastroparesis.

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