Safety, Tolerability and Pharmacokinetics of SAR113945 Following Intra-articular Administration in Patients With Knee Osteoarthritis

Study Overview
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Brief Summary
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Primary Objective: Assess the safety and tolerability of single intra-articular doses of SAR113945 in patients with knee osteoarthritis. Secondary Objective: Assess systemic exposure of SAR113945 following intra-articular delivery.

Detailed Description
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The total study duration per subject ranges from 4 to 20 weeks broken down as follows: screening within 4 weeks before dosing, follow-up of 4 weeks (28 days) after the single dose of study medication, prolonged by a maximum of 12 weeks if plasma PK level > Limit Of Quantification (LOQ) at Day 28.

Official Title
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A Double Blind, Placebo Controlled Ascending Single Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of the IKK Inhibitor, SAR113945, Following Intra-articular Administration in Patients With Knee Osteoarthritis

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: placebo
* Drug: SAR113945


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male patients or female patients of non child-bearing potential, aged at least 40 years with primary knee osteoarthritis having: X-ray or Magnetic Resonance Imaging (MRI) evidence for Kellgren Lawrence Grades II./III joint space narrowing and osteophyte formation, Western Ontario MacMaster (WOMAC) score ≦ 72, American College of Rheumatology (ACR) Clinical and Radiographic criteria for osteoarthritis. Exclusion criteria: Any uncontrolled, chronic condition or laboratory finding which, in the opinion of the Principal Investigator, could potentially put the patient at increased risk. Secondary osteoarthritis. Moderate/severe renal impairment. Underlying hepatobiliary disease and/or elevated Alanine Aminotransferase (ALT) > 3 Upper Limit of Normal range. Intra-articular injection within 3 months. Presence of local skin abnormality at the affected knee joint. Unable to be maintained for at least 2 weeks prior to entry into study on paracetamol or metamizole as analgesic. Any Investigational Product within 3 months. Any patient unlikely to comply with the requirements of the study. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR113945<br>SAR113945, single dose according to dose escalation design | Drug: SAR113945<br>* Pharmaceutical form:injection Route of administration: intra-articular<br>|
| Placebo Comparator: Placebo<br>0.9% saline solution, single dose | Drug: placebo<br>* Pharmaceutical form:injection Route of administration: intra-articular<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standard safety investigations (Physical examinations, 12 lead ECGs, vital signs (Blood pressure, heart rate, body temperature) and laboratory tests (hematology/coagulation, biochemistry, quantitative urinalysis)) |  | 4 weeks up to a maximum of 12 weeks | 
| Examination of skin/soft tissue of injected knee | Any reaction is classified as erythema, oedema, pain, papulae, haematoma and graded none, mild, moderate or severe. | 4 weeks up to a maximum of 12 weeks | 
| Examination of knee joint of injected knee | Any reaction is classified as effusion/worsening of effusion, warm and pain. | 4 weeks up to a maximum of 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters for SAR113945 and potential metabolites(s) from plasma concentration (i.e. AUC, Cmax, tmax, t1/2) |  | 4 weeks up to a maximum of 16 weeks | 
| Pharmacodynamic parameters (WOMAC Index, biomarkers relating to inflammation and cartilage/bone turnover) |  | 4 weeks |