Pain in osteoarthritic knee. MedDRA version: 13.1 Level: LLT Classification code 10049475 Term: Chronic pain System Organ Class: 10018065 - General disorders and administration site conditions
Conditions
Interventions
Product Name: LY2828360
Product Code: LY2828360
Pharmaceutical Form: Capsule*
Current Sponsor code: LY2828360
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Ph
Sponsors
Chorus, Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Are male or female patients with 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 patient at increased risk by participating in the study, and will not interfere with interpretation of the data. a Male patients: agree to use a reliable method of birth control during the study and for 3 months following the last dose of the investigational product. b Female patients: 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. Postmenopausal women: Women with an intact uterus are deemed postmenopausal if they have had cessation of menses for at least 1 year with follicle-stimulating hormone (FSH) and oestradiol values compatible with postmenopausal status, age =45 years old, and not taking oral contraceptives within the last year. [2] Between 40 and 75 years of age and body weight greater >40 kg and 50, or Morning stiffness <30 minutes, or Crepitus. d. If the patient has had an X-ray of the index joint within the last year which can confirm the diagnosis it may be used, otherwise a new anterior-posterior view x-ray should be obtained and reviewed by Principal Investigator or his delegates to verify that the patient meets the disease diagnostic criteria. [11] Have a Kellgren and Lawrence grade of I, II, III or IV. [12] 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 patient e-diary from Visi
Exclusion criteria
Exclusion criteria: ? Have an abnormality in the 12-lead ECG at screening that, in the opinion of the investigator, increases the risks associated with participation in the study. In addition, patients with following findings will be excluded: - Confirmed Bazett’s corrected QT (QTcB) interval > 450 msec for men and > 470 msec for women in 2 of 3 ECGs; additional ECGs may be performed if required, - Bundle branch blocks and other conduction abnormalities other than mild first degree atrio-ventricular block, - Irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular or rare ventricular ectopic beats, - History of unexplained syncope, - Family history of unexplained sudden death or sudden death due to long QT syndrome, - T-wave configurations are not of sufficient quality for assessing QT interval determination, as assessed by the investigator. ? 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 “Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision” (DSM-IV; APA 2000) criteria, as determined by the investigator and confirmed by the Mini-International Neuropsychiatric Interview (MINI, Sheehan et al. 1998)). ? Are judged by the Principal Investigator to be clinically at suicidal risk based upon clinical interview (Columbia-Suicide Severity Rating Scale (C-SSRS)). ? Have an alanine aminotransaminase (ALT) >2.5 times Upper Limit of Normal (ULN) at Visit 1, based on reference ranges of the local laboratory. Moderate or greater hepatic impairment. ? Have prior renal transplant, current renal dialysis or severe renal insufficiency (creatinine clearance of 1.5 times ULN, based on the reference ranges of the local laboratory. ? Have a history of or symptoms suggestive of sleep apnoea. ? Use of any known strong inducers or inhibitors of Cytochrome P450 (CYP450) within 30 days prior to enrolment. ? Are at a high risk of infection (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections and patients who are permanently bed ridden or wheelchair bound). ? Have an autoimmune disorder. ? 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 Visit 1 or have surgery planned of the index knee at anytime. ? Have had significant prior injury to the index knee within 12 months prior to Visit 1. ?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. ? Has had a prior synovial fluid analysis showing a White Blood Cell (WBC) =2000 mm3 that is indicative of a diagnosis other than OA. ? Have a confounding painful condition that may interfere with assessment of the index joint, i.e., knee. (Knee pain should be the predominant pain. Mild OA of the hands is allowed, for instance). ? Have any other musculoskeletal or arthritic condition that may affect t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and efficacy of 80 mg daily administration of LY2828360 compared to placebo on the change from baseline of pain severity (average pain scores (APS)).;Secondary Objective: To evaluate the efficacy of 80 mg LY2828360 once a day (q.d.) versus placebo during the 4-week treatment phase on the change from baseline of secondary efficacy measures. To assess the safety of 80 mg LY2828360 q.d. versus placebo during the treatment phase. To assess the Pharmacokinetics (PK) of LY2828360 in OA patients. To investigate the relationship between exposure of LY2828360 and efficacy.;Primary end point(s): Safety: Discontinuation rates, Treatment Emergent Adverse Events (TEAEs), Rescue medication, Laboratory assessments, Vital Signs (VS), Electrocardiograms (ECGs), Subjective Liking Visual Analogue Scales (SL-VAS), Addiction Research Center Inventory (ARCI) and Subjective questionnaire (Columbia-Suicide Severity Rating Scale (C-SSRS). Bioanalytical: Plasma samples to determine LY2828360 concentrations. Pharmacokinetic/Pharmacodynamic: Relationship between exposure of LY2828360 and efficacy. Efficacy: Change from baseline of pain severity as measured by the weekly mean of the daily 24-hour APS, night pain and worst daily pain, Chronic Pain Sleep Inventory (CPSI), Brief Pain Inventory (BPI), Western Ontario and MacMaster (WOMAC) OA physical function, Time and Pain intensity from the 40 m self-paced walk test, Time and Pain intensity from the 11 step stair climb test, Pittsburgh Sleep Quality Index (PSQI), Investigator and Patient Global Assessment of Changes (IGAC and PGAC) and DoloTest®. Exploratory measures: Change from baseline of EPMs: quantitative sensory testing of joint, spreading sensitization and clinical pain areas, wind-up like pain and descending noxious inhibitory control. | — |
Countries
Denmark
Outcome results
None listed