Osteoarthritic Knee Pain. MedDRA version: 14.1 Level: LLT Classification code 10029877 Term: OA knee System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Arcoxia
Pharmaceutical Form: Coated tablet
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use
Sponsors
C4Pain ApS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Written informed consent (IRB/IEC specific) has been obtained prior to initiation of any protocol required procedures. 2.Male or female between 40 and 75 years of age. Females of childbearing potential must have a negative urine pregnancy test at screening. 3.Body weight >40 kg and 50, or morning stiffness =65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: Have a history of recurrent seizures other than febrile seizures, or a history of frequent and/or severe allergic reactions with multiple medications. Have a current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, psychiatric or cerebral disease which could interfere with the subject's participation in the study. At screening, have an abnormality in the 12-lead ECG that increases the risks associated with participation in the study. In addition, subjects with following findings will be excluded: a. Confirmed Bazett’s corrected QT (QTcB) interval > 450 msec for men and > 470 msec for women at screening. b. Bundle branch blocks and other conduction abnormalities other than mild first degree atrio-ventricular block, left anterior hemi block due to left axis deviation and right bundle branch block of benign origin i.e. not caused by other cardiac disease, c. Irregular rhythms other than sinus arrhythmia or occasional supraventricular or ventricular ectopic beats, d. History of unexplained syncope. Family history of unexplained sudden death or sudden death due to long QT syndrome, f. T-wave configurations are not of sufficient quality for assessing QT interval determination. Have an ALAT >2.5 timer ULN at screening. Have prior renal transplant, current renal dialysis or severe renal insufficiency ( determined by GFR), or serum creatinine laboratory value >1.5 times ULN. Have active peptic ulcer or gastrointestinal (GI) bleeding. Have known inflammatory intestinal disease. Subject with ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease or with congestive heart failure (NYHA II-IV). Subject with uncontrolled arterial hypertension (>160/90) diabetes mellitus and atherosclerosis. History of bronchospasms, acute rhinitis, nasal polyps, angioneurotic edema, urticaria or other type of allergic reaction after having used acetylic acid or NSAID, inclusive COX-2 inhibitors. Allergic to the active ingredient of etoricoxib or one or more of the excipients. Pregnant female or breast feeding. Subject with an active malignancy of any type or a history of malignancy within the last 5 years (except basal cell carcinoma of the skin that has been excised prior to study start). Are taking any excluded medications (analgesic medications) that cannot be discontinued during the screening period (3 days prior to visit 2). Subject in treatment with anticoagulants (with the exception of acetylsalicylic acid), methotrexate or rifampicin or antihypertensiva (with the exception of Ca+-antagonists). Have received treatment within the last 30 days with an investigational study drug Have a history of substance abuse or dependence within the past year, excluding nicotine and caffeine. Subject at a high risk of infection (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections and subjects who are permanently bed ridden or wheelchair bound). Subject with a history of, or suspected, demyelinating disease of the central nervous system (e.g. multiple sclerosis or optic neuritis). Have an autoimmune disorder (not including psoriasis). Subject that do not fully understand the EPM procedures according to investigator experience. Investigator site personnel directly affiliated with this study and/or their immediate family cannot participate. Subject dia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess which pain mechanisms are modulated by 60 mg daily administration of etoricoxib compared to placebo in subjects with osteoarthritic (OA) knee pain during two treatment periods of 4-weeks each. ;Secondary Objective: To evaluate if changes in any of the mechanism based experimental pain assessment parameters can explain changes in clinical outcome parameters. To profile drug responders- versus non-responders based on pain mechanisms involved. To investigate if change in inflammatory, bone and cartilage related bio-chemical biomarkers can explain changes in either experimental or clinical pain parameters. ;Primary end point(s): As the primary objective of this study is assessment of which pain mechanisms are modulated by study drug administration, the primary endpoints will include Experimental mechanism based Pain Measures (EPMs) as listed below: • Quantitative Sensory Testing (QST) of joint pain (pressure pain thresholds from 3 knee joint locations of most painful side) • Spreading sensitization (pressure pain threshold from tibialis anterior of the most painful knee and from the extensor carpi radialis longus muscle on the ipsilateral site) • Pain areas (area of pain drawings) • Wind-up like pain (repeated mechanical pressure stimulation to the most painful knee site and tibialis anterior muscle) • Descending noxious inhibitory control (combining pressure pain at the knee, leg and arm and pressure pain to cuff inflation) • Cuff evoked pain (cuff algometry) • Infrared thermography of both knees (medial, frontal and lateral views) ;Timepoint(s) of evaluation of this end point: Subjects will be randomized to one of the 2 sequences of treatment: Sequence 1 (60 mg/day etoricoxib followed by placebo) or Sequence 2 (placebo followed by 60 mg/day etoricoxib). The two treatment periods of 4 weeks each are separated by a washout period of at least 6 days. Pain Models (EPMs) to be performed at: visit 3, 5, 6 and 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change of pain severity from baseline to end of study, as measured by the weekly mean of the daily 24-hour average pain score (APS), night pain and worst daily pain, Pain Quality Assessment Scale (PQAS), Brief Pain Inventory (BPI), Investigator and Patient Global Assessment of Changes (IGIC and PGAC), Western Ontario and McMaster (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, DoloTest® and PainDetect. Fasting plasma, serum and urine samples will be collected and stored for potential further analysis of e.g. IL-6, IL-8, CTX1, CTX2, TNFa, CCL2, CO1, CO2, sCRP, CRP25, C1M, C2M, C3M, OC, MMP. ;Timepoint(s) of evaluation of this end point: Timepoints for questionnaires: PQAS, IGIC and PGAC; visit 3, 4, 5, 6, 7, and 8 BPI, WOMAC, self-paced walk test, stair climb test, DoloTest and PD-Q; visit 1, 3, 5, 6 and 8 Inflammatory, bone and cartilage related bio-chemical biomarkers; visit 3, 5, 6 and 8 | — |
Countries
Denmark
Contacts
Public ContactBettina Storgaard Nedergaard
CCBR A/S
Outcome results
None listed