Clinical trial NCT01319929: A Study of LY2828360 in Patients With Osteoarthritic Knee Pain
Official title: A Proof of Concept Study of the Effects of LY2828360 in the Treatment of Patients With Osteoarthritic Knee Pain.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Keywords: Osteoarthritis, knee pain, osteoarthritic knee pain
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-03-22
Enrollment: 39
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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


Eligibility criteria: 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)

Primary outcomes:
measure: Change From Baseline to 4 Week Endpoint in Weekly Mean of Daily 24-Hour Average Pain Scores (APS)
timeFrame: Baseline, 4 weeks
Secondary outcomes:
measure: Pharmacokinetics (PK) of LY2828360: Maximal Concentration (Cmax)
timeFrame: Pre-last dose to 8 hours post-last dose (at end of each 4-week treatment period)
measure: Pharmacokinetics (PK) of LY2828360: Area Under the Concentration-Time Curve (AUC)
timeFrame: Pre-last dose to 8 hours post-last dose (at end of each 4-week treatment period)
measure: Change From Baseline to 4 Week Endpoint in Weekly Mean of Night Pain and Worst Daily Pain Scores
timeFrame: Baseline, 4 weeks
measure: Change From Baseline to 4 Week Endpoint in Chronic Pain Sleep Inventory (CPSI)
timeFrame: Baseline, 4 weeks
measure: Change From Baseline to 4 Week Endpoint in Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Baseline, 4 weeks
measure: Change From Baseline to 4 Week Endpoint in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I)
timeFrame: Baseline, 4 weeks
measure: Change From Baseline to 4 Week Endpoint in Investigator Global Assessment of Changes (IGAC)
timeFrame: Baseline, 4 weeks
measure: Change From Baseline to 4 Week Endpoint in Patient Global Assessment of Changes (PGAC)
timeFrame: Baseline, 4 weeks
measure: Change From Baseline to 4 Week Endpoint in Western Ontario and MacMaster (WOMAC)
timeFrame: Baseline, 4 weeks
measure: Change From Baseline to 4 Week Endpoint in Pain From 40 Meter Self-Paced Walk Test
timeFrame: Baseline, 4 weeks
measure: Change From Baseline to 4 Week Endpoint in the 11 Step Stair Climb Test
timeFrame: Baseline, 4 weeks
measure: Change From Baseline to 4 Week Endpoint in DoloTest Sum Score
timeFrame: Baseline, 4 weeks
measure: Number of Participants With Treatment-Emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to 15 weeks
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri 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: