Moderate to severe chronic pain due to knee osteoarthritis with or without neuropathic component. MedDRA version: 19.0 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Name: CR4056
Product Code: CR4056
Pharmaceutical Form: Capsule
INN or Proposed INN: CR4056
CAS Number: 1004997-71-0
Current Sponsor code: CR4056
Other descriptive name: CR4056
Concentration un
Sponsors
Rottapharm Biotech S.r.l.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated informed consent obtained before undergoing any trial-specific procedure 2. Male or female aged =40 years and =75. 3. Diagnosis of primary OA of the knee of =6 months before the Screening Visit. The diagnosis must be confirmed at Screening Visit based on American College of Radiology (ACR) clinical and radiological criteria (X-ray must be performed during Screening Visit if not already available in the 24 months preceding the study): -Knee pain -X-ray osteophytes and at least one of the following: age >50 years morning stiffness =65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: 1. Rheumatological diseases other than OA (e.g., rheumatoid arthritis, other inflammatory arthritis, acute joint trauma, gout, pseudo gout, Paget’s disease). 2. Clinical diagnosis of fibromyalgia. 3. Severe pain (regardless of the location of pain) caused by other diseases, trauma, or surgery. 4. In case of multiple painful OA joints, primary location of pain other than the knee. 5. Joint replacement at any knee. 6. Significant surgical procedures (other than joint replacement) at any knee =12 months before the Screening Visit. 7. Planned surgical procedure at any knee during the study. 8. Thrombocytopenia or any coagulation or hematopoietic disease. 9. Seizure (excluding pediatric febrile seizures), schizophrenia, bipolar disorder, uncontrolled major depression, generalized anxiety disorder (=6 months before the Screening Visit). Patients who are on stable therapy for depression or anxiety (except on the medications reported in Appendix IV) are eligible for the study. 10. Cardiac arrhythmia, congestive heart failure, coronary heart disease, class III/IV angina, acute myocardial infarction (=6 months before the Screening Visit). 11. Acute hepatitis (=3 months before the Screening Visit), chronic hepatitis and HIV infection. 12. Malignancy (other than basal cell carcinoma of the skin) active =12 months before the Screening Visit. 13. Patients with a personal or a family history of gallstone disease. 14. Stroke, intracranial hematoma, moderate or severe traumatic brain injury (Glasgow coma scale <13 or loss of consciousness for more than 30 minutes) or an intracranial operation =12 months before the Screening Visit. 15. History of alcohol or drug abuse =12 months before the Screening Visit. 16. Known allergy or hypersensitivity to paracetamol. 17. Significant respiratory disease (if treatment with prohibited medication, e.g. systemic steroids, is required) 18. Gastrointestinal diseases that are known to interfere with the absorption or excretion of medications. 19. Any clinically relevant disease that in the Investigator’s opinion may affect efficacy or safety assessments or may compromise the subject’s safety during trial participation, (gastrointestinal, blood, endocrine, metabolic, neurological, or psychiatric disorders). 20. Platelet count <200.000/µL. 21. Serum alkaline-phosphatase, or gamma-glutamyl-transferase, or lipase greater than 3-fold the upper limit of normal (ULN); alanine aminotransferase, or aspartate aminotransferase, or total bilirubin greater than 2-fold ULN. 22. Estimated creatinine clearance less than 60 mL/min/1.73 m2 (MDRD). 23. 12-lead electrocardiogram (ECG) with clinically relevant findings. 24. Treatment with strong opioids (=30 days before the Screening Visit). Patients who are taking weak and atypical opioids can be enrolled in the study. 25. Intra-articular visco-supplementation at any knee (=6 months before the Screening Visit). 26. Intra-articular or topical steroids, topical NSAIDs at any knee (=3 months and = 1 week before the Screening Visit, respectively). 27. Oral or parenteral steroids (=3 months before the Screening Visit). Inhaled and topical steroids are allowed. 28. SYSADOA (e.g. glucosamine, chondroitin sulfate, or others), unless administration of the same product (brand and dosage) is stable for at least 3 months prior to Screening Visit. 29. Other prohibited medications (unless the patient can suspend therapy for the duration of the study) 30. For women of chil
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of CR4056 on pain (with or without a neuropathic component) in patients with osteoarthritis (OA) of the knee.;Secondary Objective: To evaluate the safety and tolerability of CR4056 in patients with OA of the knee.;Primary end point(s): Mean change from baseline (randomization) in the WOMAC Pain Subscale score (normalized to 0-100 scores) at the end of the double blind treatment period.;Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated after 2 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated after 1 and 2 weeks of treatment.;Secondary end point(s): - Mean change from baseline in the WOMAC Pain Subscale score (normalized to 0-100 scores) at week 1. - Mean change from baseline in the first question of the WOMAC Pain Subscale score (normalized to 0-100 scores) at week 1 and 2. - Mean change from baseline in the WOMAC Stiffness Subscale score (normalized to 0-100 scores) at week 1 and 2. - Mean change from baseline in the WOMAC Physical Function Subscale score (normalized to 0-100 scores) at week 1 and 2. - Mean change from baseline in the WOMAC Total Index score (normalized to 0-100 scores) at week 1 and 2. - Mean change from baseline in the severity of daily knee pain (separately for right and left knee), as measured by the 11-point NRS, at weeks 1 and 2. - Number of patients reporting from baseline a knee pain reduction of at least 30%, i.e. a 30% decrease in the daily knee pain (separately for right and left knee) as measured by the 11-point NRS, at week 1 and 2. - Mean change from baseline in the Patient’s Global Assessment of his/her arthritis at weeks 1 and 2. - Mean change from baseline in the time needed to perform the 40 meters walking test at week 1 and 2. - Mean change from baseline in the severity of knee pain (separately for right and left knee), as measured by 11-point NRS, after the completion of the 40 meters walking test at week 1 and 2. - Number of responder patients according to the OARSI-OMERACT Response Criteria (Pham et al, 2004) at week 1 and 2. This set of response criteria will be applied in the present study considering the WOMAC Pain Subscale, the Patient’s Global Assessment of Arthritis and the WOMAC Physical Function subscale at week 1 and 2. - Number of patients using rescue medication at week 1 and 2. | — |
Countries
Poland
Contacts
Public ContactClinical Research Manager
Rottapharm Biotech S.r.l.
Outcome results
None listed