Clinical trial NCT00790790: A Study in the Treatment of Osteoarthritis Knee Pain
Official title: A Phase 2 Study of the Effects of LY545694, an iGluR5 Antagonist, in the Treatment of Subjects With Osteoarthritis Knee Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis Knee Pain
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-11-14
Enrollment: 147
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To gather data on whether a new drug for osteoarthritis knee pain will be safe and have an effect on pain levels.


Eligibility criteria: Inclusion Criteria:

* Present with Osteoarthritis (OA) of the knee based on: 1) Knee pain for at least 14 days per month for the last 3 months, 2) Osteophytes (bone spurs), 3) And at least 1 of the following: Over the age of 50, OR morning stiffness in knee for less than 30 minutes, OR crunching sensation as the knee bends back and forth (crepitus).
* Mean score of 4 or greater on the 24-hour average pain score from Visit 2 to Visit 3.
* Completion of electronic daily diaries with at least 70% complete between Visit 2 and Visit 3.
* Taken non-steroidal anti-inflammatory drugs (NSAIDs) less than 15 days over the past month AND not taken NSAIDs at least 1 week prior to Visit 3.
* Agree to maintain the same activity level throughout the study.
* Women who can become pregnant must test negative for pregnancy and agree to utilize medically acceptable/reliable birth control during the study and 1 month following the last dose of the study.
* Competent and freely able to give an informed consent.
* Ability to understanding and intelligibly communicate with the investigator.
* Judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol.

Exclusion Criteria:

* Knee arthroscopy within past 3 months or any knee joint replacement.
* Surgery planned during the trial for the knee to be studied.
* Prior synovial fluid analysis showing a white blood cell of 2000 cubic millimeters (mm\^3) that is indicative of a diagnosis other than OA
* Are non-ambulatory or require the use of crutches or a walker. Use of a cane in the hand opposite the index knee is acceptable.
* Body Mass Index over 40.
* Confounding painful condition that may interfere with assessment of the index knee. (Knee pain should be the predominant pain. Mild OA of the hands is allowed, for instance.)
* Diagnosis of inflammatory arthritis (rheumatoid arthritis) or an autoimmune disorder (except inactive Hashimoto's thyroiditis).
* Received intra-articular hyaluronate or steroids, joint lavage, or other invasive therapies to the knee in the past 3 months.
* Frequent falls that could result in hospitalization or could compromise response to treatment.
* Current or previous (within the past 1 year) Axis 1 diagnosis of major depressive disorder, mania, bipolar disorder, psychosis, dysthymia, anxiety disorder, alcohol or eating disorders.
* Serious or unstable cardiovascular, hepatic, renal, respiratory, ophthalmologic, gastrointestinal, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition that in the opinion of investigator would compromise participation or be likely to lead to hospitalization during the course of the study.
* Alanine transaminase (ALT) \> 2.0 times upper limit of normal at Visit 1, based on reference ranges of the central lab.
* Prior renal transplant, current renal dialysis, or serum creatinine laboratory value \>1.5 times upper limit of normal based on the reference ranges of the central lab.
* Diagnosis or past history of glaucoma. Subjects with intraocular pressure \>24 millimeters of mercury (mm Hg).
* Are taking any excluded medications that cannot be discontinued at Visit 1.
* History of substance abuse or dependence within the past year, excluding nicotine and caffeine. Have a positive urine drug screen for any substance of abuse or excluded medication.
* History of recurrent seizures other than febrile seizures.
* Are judged by the investigator to be at suicidal risk.
* History of frequent and/or severe allergic reactions with multiple medications.
* Pregnant or breast-feeding.
* Are unwilling/unable to comply with the use of a data collection devices.
* 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.
* Investigator site personnel directly affiliated with this study, and/or their immediate families, or Lilly employees.
* History of severe delay in stomach emptying (gastroparesis).

Primary outcomes:
measure: Change From Baseline in Weekly Mean 24-hour Average Pain Severity (APS) Score From Electronic Diary at 5 Weeks
timeFrame: Baseline, 5 weeks
Secondary outcomes:
measure: Change From Baseline in Weekly Mean Night Pain Severity Score From Electronic Diary at 5 Weeks
timeFrame: Baseline, 5 weeks
measure: Change From Baseline in Weekly Mean Worst Daily Pain Severity Score From Electronic Diary 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 Clinical Global Impression of Severity (CGI-S) Score at 5 Weeks
timeFrame: Baseline, 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: Patient Global Impression of Improvement (PGI-I) Score at 5 Weeks
timeFrame: Week 5
measure: Change From Baseline in Assessment of Sleep Questionnaire (ASQ) Total Score at 5 Weeks
timeFrame: Baseline, 5 weeks
measure: Change From Baseline in Total Western Ontario and MacMaster (WOMAC) Osteoarthritis Physical Function, Pain, and Stiffness Subscales 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 in 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 Treatment Emergent Adverse Events (TEAEs) During the Therapy Phase and 1-Week Washout 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 (ECG) Change in Heart Rate Using Bazett's (QTcB) and Fridericia's (QTcF) Formulas
timeFrame: Baseline through 5 weeks
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: Number of Participants With Neurological Treatment Emergent Adverse Events (AEs)
timeFrame: Baseline through 5 weeks
measure: Time to Response
timeFrame: Baseline through 5 weeks
Other outcomes:
Locations:
city: Spring Valley
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: South Miami
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: Edison
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: New Jersey
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: Brasov
country: Romania
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: Bucharest
country: Romania
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: Iasi
country: Romania
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: Targu-Mures
country: Romania
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: