Osteoarthritic Knee Pain. MedDRA version: 18.0 Level: LLT Classification code 10029877 Term: OA knee System Organ Class: 100000004859
Conditions
Interventions
Trade Name: Palexia Depot
Pharmaceutical Form: Tablet
INN or Proposed INN: Tapentadol
CAS Number: 175591-23-8
Current Sponsor code: Palexia SR
Other descriptive name: TAPENTADOL
Concentration unit: mg
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 80 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 12
Exclusion criteria
Exclusion criteria: 1. A history of recurrent seizures other than febrile seizures. 2. A history of frequent and/or severe allergic reaction with multiple medication. 3. A current or recent history, as determined by the investigator or his delegates, of severe, progressive, and/or uncontrolled renal, including severe renal impairment, hepatic, including severe impaired liver function, hematological, gastrointestinal, endocrine, pulmonary, including respiratory depression, COPD or acute severe asthma, cardiac, including cor pulmonale, neurological, psychiatric or cerebral disease which could interfere with the subject's participation in the study. 4. At screening, have an abnormality in the 12-lead ECG that, in the opinion of the investigator, 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: i) mild first degree atrio-ventricular block, ii) left anterior hemi block due to left axis deviation, iii) 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, e. 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, as assessed by the investigator. 5. An alanine aminotransaminase. Moderate or greater hepatic impairment. 6. Prior renal transplant, current renal dialysis or severe renal insufficiency or serum creatinine. 7. Pregnant female, breast feeding or planning a pregnancy during the study period. Females of child-bearing potential, not using a reliable means of contraception (refer to section 8.5.3 – reliable contraception). 8. 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). 9. Any excluded medications (analgesic medications) that cannot be discontinued during the screening period (3 days prior to visit 2). 10. Treatment within the last 30 days with a drug that has not received regulatory approval. 11. Substance abuse or dependence, not nicotine/caffeine. 12. A high risk of infection. 13. A history of, or suspected, demyelinating disease of the central nervous system. 14. An autoimmune disorder. 15. Not fully understand the EPM procedures. 16. Investigator site personnel directly affiliated with this study and/or their immediate family. 17. Diagnosed with any condition suggestive of a secondary cause of knee OA. 18. History of surgery in the index knee within 3 months or planned surgery. 19. Complicated prior injury to the index knee within 12 months. 20. Diagnosed with Kellgren and Lawrence grade 0 or IV. 21. Use of lower extremity assistive devices. 22. Prior synovial fluid analysis showing a WBC=2000mm. 23. A confounding painful condition that may interfere with assessment. 24. 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. 25. Have used corticosteroids prior to baseline: a. Intra-articular injection of steroids into the index knee or in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess which pain mechanisms (with specific focus on the descending inhibition) are modulated by daily administration of 2 x 100-250 mg tapentadol PR compared to 2 x 20-50 mg oxycodone CR in subjects with osteoarthritic (OA) knee pain during a treatment period of 4-weeks (preceded to a titration period of up to 15 days). ;Secondary Objective: To evaluate if changes in any of the mechanism based experimental pain assessment parameters can explain changes in clinical outcome parameters (reduction in clinical pain intensity). To profile drug responders- versus non-responders based on pain mechanisms involved. ;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) ;Timepoint(s) of evaluation of this end point: Subjects will be randomized to one of two treatment arms: Arm 1 (titrated from 50 mg up to max. 250 mg x 2/day tapentadol PR). or Arm 2 (titrated from 10 mg up to max. 50 mg x 2/day oxycodone CR). The treatment period is 4 weeks preceded by an up to 15 day's titration. Experimental mechanism based Pain Measures (EPMs) to be performed at visit: 3 and 6. A demonstration of the tests at visit 2. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change of pain severity from baseline to end of the 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.;Timepoint(s) of evaluation of this end point: Timepoints for questionaires: PQAS, IGIC and PGAC; visit 3 and 6. BPI, WOMAC, self-paced walk test, stair climb test, DoloTest and PD-Q; visit 1, 3, 5 and 6. | — |
Countries
Denmark
Contacts
Public ContactBettina Storgaard Nedergaard
CCBR A/S
Outcome results
None listed