A Study of LY2828360 in Patients With Osteoarthritic Knee Pain

Lilly

Status and phase

Completed

Phase 2

Conditions

Osteoarthritis, Knee

Treatments

Drug: LY2828360

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT01319929

I4F-EW-CCAC (Other Identifier)

14165

Details and patient eligibility

About

To investigate the safety, efficacy and pharmacokinetics of single daily oral dose of LY2828360 in male and female subjects with osteoarthritic knee pain

Enrollment

39 patients

Sex

All

Ages

40 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Are male or female participants with osteoarthritis (OA), as determined by medical history and physical examination. Males and females with stable medical problems that, in the investigator's opinion, will not significantly alter the disposition of the drug, will not place the participant at increased risk by participating in the study, and will not interfere with interpretation of the data.
1. Male participants: agree to use a reliable method of birth control during the study and for 3 months following the last dose of the investigational product
2. Female participants: women not of child-bearing potential due to surgical sterilization (at least 6 weeks post surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history, or menopause
Body weight greater than 40 kilograms (kg) and less than 120 kilograms (kg) with a body mass index (BMI) between 19-35 kilograms per square meter (kg/m^2) inclusive
Participant with osteoarthritic knee based on disease diagnostic criteria as presented in the Inclusion Disease Criteria, below
Blood pressure and pulse rate in supine and standing positions, within normal reference ranges for the population and investigator clinical research unit (CRU), or results with acceptable deviations that are judged to be not clinically significant by the investigator
Have clinical laboratory test results within normal reference range for the population or investigator clinical research unit (CRU), or results with acceptable deviations that are judged to be not clinically significant by the investigator
Have venous access sufficient to allow for blood sampling
Have agreed to maintain the same activity level throughout the course of the study

Inclusion Disease Criteria:

Have a unilateral or bilateral osteoarthritis (OA) of the knee diagnosed according to the American College of Rheumatology (ACR) criteria. The clinical diagnosis of osteoarthritis (OA) will be confirmed by the American College of Rheumatology (ACR) clinical and radiographic criteria for classification of idiopathic osteoarthritis (OA) of the knee based upon the following criteria:
1. Knee pain for at least 14 days per month for the 3 months before screening
2. Osteophytes (with radiographic evidence)
3. At least 1 of the following 3 conditions: Age greater than 50, or Morning stiffness less than 30 minutes, or Crepitus
Have a Kellgren and Lawrence grade of I, II, III or IV
Have a mean score of at least 4 (moderate) and less than or equal to 8 (moderate-severe) on the 24-hour average pain score (0-10) (question 1) in the participant e-diary from screening to randomization for the knee joint during walking
Discontinued use of all analgesic medications (including over-the-counter [OTC] analgesics/Non-Steroidal Anti-Inflammatory Drug [NSAID]) at least 2 weeks prior to randomization (participants are allowed limited use of analgesic medications)

Exclusion criteria

Are currently enrolled in, have completed or discontinued within the last 3 months from, a clinical trial involving an off-label investigational drug or device or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Have known allergies to LY2828360, related compounds or any components of the formulation
Have an abnormality in the 12-lead electrocardiogram (ECG) at screening that, in the opinion of the investigator, increases the risks associated with participation in the study
Have a recent or current history of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
Have current or previous (within the past year) Axis 1 diagnosis of major depressive disorder, mania, bipolar disorder, psychosis, dysthymia, generalized anxiety disorder, alcohol or eating disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision, criteria, as determined by the investigator and confirmed by the Mini-International Neuropsychiatric Interview
Are judged by the Principal Investigator to be clinically at suicidal risk based upon clinical interview
Have intercurrent illness or clinically significant adverse events
Have increased risk of seizures as evidenced by a history of seizures, stroke, surgery to the cerebral cortex, or head trauma with loss of consciousness
Have an alanine aminotransaminase (ALT) greater than 2.5 times Upper Limit of Normal (ULN) at Screening, based on reference ranges of the local laboratory. Moderate or greater hepatic impairment
Have prior renal transplant, current renal dialysis or severe renal insufficiency, or serum creatinine laboratory value greater than 1.5 times Upper Limit of Normal, based on the reference ranges of the local laboratory
Have clinically significant abnormal neurological examination, especially any evidence of tremor or nystagmus
Have a history of or symptoms suggestive of sleep apnoea
Use of any known strong inducers or inhibitors of Cytochrome P450 within 30 days prior to enrolment.
Regularly use known drugs of abuse and/or show positive findings on urinary drug screening
Have a positive alcohol breath test at Screening
Show evidence of human immunodeficiency virus infection and/or positive human HIV antibodies
Have an active malignancy of any type or a history of malignancy (except basal cell carcinoma of the skin that has been excised prior to study start)
Are at a high risk of infection
Have an autoimmune disorder
Show evidence of hepatitis C and/or positive hepatitis C antibody
Show evidence of hepatitis B and/or positive hepatitis B surface antigen
Are women with a positive pregnancy test or women who are lactating or child bearing
Use prescription and herbal medications that cannot safely be discontinued by end of screening
Have donated blood of more than 500 milliliters (mL) within the last 3 months
Have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females), or are unwilling to refrain alcohol consumption for the duration of the study
Are persons who have previously received the investigational product in study, have completed or withdrawn from this study or any other study investigation LY2828360
Are taking any excluded medications (analgesic medications) and over-the- counter medications that cannot be discontinued at screening
Show evidence or have any prior history of significant active neurological or psychiatric disease including depression

Exclusion Disease Criteria:

Have secondary causes of arthritis of the knee including septic arthritis, inflammatory joint disease, articular fracture, major dysplasias or congenital abnormality, ochronosis, acromegaly, hemochromatosis, Wilson's disease, and primary osteochondromatosis
Have had lower extremity surgery (including arthroscopy of the index knee) within 6 months prior to Screening or have surgery planned of the index knee at anytime
Have had significant prior injury to the index knee within 12 months prior to Screening
Use of lower extremity assistive devices other than a cane or knee brace (use of a 'shoe lift' is permitted). 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
Have a confounding painful condition that may interfere with assessment of the index joint, that is, knee
Have any other musculoskeletal or arthritic condition that may affect the interpretation of clinical efficacy and/or safety data or otherwise contraindicates participation in this clinical study
Have used corticosteroid prior to baseline
Have received hyaluronan injections into index knee within the previous 6 months prior to Treatment Phase day 3
Have initiated or have changed to an established physiotherapy program within 2 weeks prior to Treatment Phase day 3 or during the study period An established physiotherapy program may be continued throughout the study period if unchanged in frequency and intensity
Has had a prior synovial fluid analysis showing a White Blood Cell (WBC) greater than or equal to 2000 cubic millimeters (mm^3) that is indicative of a diagnosis other than OA
Have started recently or changed dose regimen of any OA specific therapies (that is, nutraceutical products)

Trial design

Primary purpose

Other

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Double Blind

39 participants in 2 patient groups

LY2828360 then Placebo

Experimental group

Description:

80 milligrams (mg) of LY2828360 daily by mouth for 4 weeks: placebo daily by mouth for 4 weeks. There is a washout period of 3 weeks between treatments.

Treatment:

Drug: Placebo

Drug: LY2828360

Placebo then LY2828360

Experimental group

Description:

Placebo daily by mouth for 4 weeks: LY2828360 daily by mouth for 4 weeks. There is a washout period of 3 weeks between treatments.

Treatment:

Drug: Placebo

Drug: LY2828360