A Study in the Treatment of Osteoarthritis Knee Pain

Lilly

Status and phase: Completed; Phase 2

Conditions: Osteoarthritis Knee Pain

Treatments: Drug: Placebo; Drug: LY545694 49 mg; Drug: LY545694 105 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00790790

11978

H8C-MC-LQBG(a) (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 147 patients

Sex: All

Ages: 40 to 70 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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147 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants randomized to LY545694 placebo were given LY545694 placebo twice daily (BID) oral (po) for 5 weeks.

Treatment:

Drug: Placebo

LY545694 49 mg

Experimental group

Description:

Participants randomized to LY545694 49 milligrams (mg) BID po were first administered LY545694 21 mg BID po at Visit 3. After 1 week of dosing, participants were escalated to LY545694 49 mg BID po at Visit 4. Participants who were intolerant of this dose were titrated back down to 21 mg BID po for the remainder of study treatment.

Treatment:

Drug: LY545694 49 mg

LY545694 105 mg

Experimental group

Description:

Participants randomized to LY545694 105 mg BID po were first administered LY545694 21 mg BID po at Visit 3. After 1 week of dosing, participants were escalated to LY545694 49 mg BID po at Visit 4. At Visit 5, participants were titrated to the final dose of LY545694 105 mg BID po. Participants who were intolerant of this dose were titrated back down to LY545694 49 mg BID po for the remainder of study treatment.

Treatment:

Drug: LY545694 105 mg