Ostoarthritis of the knee MedDRA version: 14.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Name: Fasitibant chloride bis-hydrochloride
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Fasitibant chloride (as bis-hydrochloride)
CAS Number: 883969-00-4
Current Sponsor
Sponsors
Menarini Ricerche S.p.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Written informed consent. 2.Male or female patients = 30 years old and a BMI 5 points assigned to the index knee at WOMAC NR 3.1-A1. 6. Pain score >12 points assigned to the index knee at WOMAC NR 3.1 A subscore. 7. Pain in the index knee on at least 50% of the days in the month preceding the screening. 8. Minimum flexion of 90 degrees in both knees. 9. Ability to perform the 15 m walk test without the support of crutches or other assistive devices. 10. Willingness to discontinue all pain or OA medication. 11. Willingness to refrain from paracetamol use 48 hours prior to each study visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. Inability to personally provide written informed consent. 2. Inability to understand or collaborate throughout the study. 3. Patients who participated in another clinical trial within 30 days prior randomisation. 4. Patients with severe OA of the knee. 5. Knee condition representing an indication for surgery . 6. Inflammatory or crystal arthropathies. 7. Patients with acute fractures, severe loss of bone density, bone necrosis. 8. Patients with isolated patella-femoral syndrome or chondromalacia. 9. Patients with OA predominant in the lateral compartment. 10. Patients with any other clinically significant and unstable disease or condition interfering with the evaluation of the safety of study treatment. 11. Major injury or surgery to the index knee within the previous 12 months prior to screening. 12. Severe hip OA ipsilateral to index knee. 13. Any pain >3 points in the numerical rating (NR) scale (0-10) that could interfere with the assessment of the index knee pain. 14. Any pharmacological or non-pharmacological treatment started or changed during 4 weeks prior to randomisation. 15. Use of systemic or topical corticosteroids >10 mg prednisolone equivalent. 16. Use of any pain or OA medication. 17. Any acute or newly diagnosed disease/condition requiring treatment. 18. Any unstable chronic disease/condition requiring treatment modification. 19. History of hypersensitivity to drugs including paracetamol. 20. Patient with known hypersensitivity to hyaluronate preparations. 21. Patients with any of the following a) clinically relevant cardiovascular, pulmonary, gastrointestinal, haematological, neurologic-psychiatric or infectious diseases. b) clinically relevant abnormal safety laboratory test result and/or clinically relevant abnormalities in vital signs and/or ECG parameters at screening (Visit 1) and/or prior to dose administration (Visit 2). 22. Patients with liver disease 23. Patients with moderate or severe renal insufficiency (Creatinie Clearence [CrCl according to Cockgroft-Gault formula] < 60 mL/min). 24. Any sign of significant inflammation or infection. 25. Any skin disorder or infection overlying the index knee. 26. Previous infection of the index knee. 27. Any IA or local peri-articular punction, injection, or surgery to the index knee during the 3 months prior to screening. 28. Patients with bleeding diathesis or on therapy with anticoagulants. 29. Significant peri-articular calcification. 30. Previous ligament reconstruction at the index knee.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of fasitibant up to 5 mg formulated as 1 mL solution to be given as single intra-articular (IA) administration to patients with knee osteoarthritis.;Secondary Objective: 1) To assess main plasma pharmacokinetic parameters, including dose-proportionality of fasitibant monocomponent (up to 5 mg), of its main metabolite MEN 19148, and of fasitibant 5 mg in extemporaneous combination with sodium hyaluronate in patients with knee osteoarthritis (OA). 2) To evaluate changes in plasma or serum levels, as appropriate,of OA biomarkers and preliminary efficacy data in knee OA patients following IA single up to 5 mg doses of fasitibant alone and in combination with Sodium Hyaluronate.;Primary end point(s): Safety and tolerability of study treatments: -Changes in vital signs (blood pressure, pulse rate, respiratory rate, body temperature; 12-lead electrocardiogram (ECG) parameters; laboratory safety battery tests, and physical examination at End of Study versus baseline. -Incidence and severity of adverse events occurring between randomisation and End of Study. ;Timepoint(s) of evaluation of this end point: Between randomisation (T0) and two weeks after administration of study treatments (T14 +/- 2 Days). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetics of the study treatments in terms of absorption, distribution, metabolism and elimination of the study treatments, including analysis of dose proportionality. This includes also the pharmacokinetic analysis of the main metabolite of fasitibant (MEN 19148), the mono-hydroxylated derivative formed by oxidative metabolism by the cytochrome P450 enzyme. Pharmacodynamics of the study treatments: Analysis of Biomarkers of osteoarthritis, inflammation and cartilage degeneration. Clinical Efficacy of study treatments: Assessment of OA symtoms (pain, walking pain, stiffness) using validated standard questionnaires (WOMAC 3.1 NR). Assessment of pain at rest and after 15 metres walk Patients' and Physicians' global assessment of efficacy. ;Timepoint(s) of evaluation of this end point: Pharmacokinetics: Between time of dosing (T0) and defined time points until 1 week (T7 +/-2 days) after treatment adminsitration. Pharmacodynamics: OA Biomarkers: Between time of dosing (T0) and 1 week (T7 +/-2 days) after treatment adminsitration. Clinical Efficacy: Between time of dosing (T0), 1 week (T7 +/-2 days) and 2 weeks (T14 +/-2 days) after treatment adminsitration. | — |
Countries
Germany
Contacts
Public ContactClinical Research Director
Menarini Ricerche S.p.A
Outcome results
None listed