Safety, Tolerability and Pharmacokinetics of SAR113945 in Japanese Patients With Knee Osteoarthritis

Study Overview
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Brief Summary
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Primary Objective: To assess the safety and tolerability of SAR113945 in Japanese patients with knee osteoarthritis after ascending single intra-articular doses Secondary Objective: To assess the pharmacokinetics of SAR113945 in Japanese patients with knee osteoarthritis after ascending single intra-articular doses

Detailed Description
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Following the single dose of study medication, the study period for each patient will be 168 days.

Official Title
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A Randomized, Double-blind, Placebo-controlled Ascending Single Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SAR113945 (IKK Inhibitor) Following Intra-articular Administration in Japanese Patients With Knee Osteoarthritis

Conditions
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Knee 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: Japanese male or female patients, aged 40 years or older, with knee osteoarthritis Diagnosis of primary knee osteoarthritis, based upon the following: X-ray or magnetic response imaging (MRI) evidence within the last 6 months for joint space narrowing and osteophyte formation Patients will be Kellegen and Lawrence classification II or III, and total Western Ontario McMaster (WOMAC) score below or equal to 72 Patients fulfilling the American College of Rheumatology Clinical and Radiographic criteria for Osteoarthritis Exclusion criteria: Women of child bearing potential Secondary osteoarthritis: e.g., autoimmune disease, joint dysplasia, aseptic osteonecrosis, acromegaly, Paget's disease, Ehlers-Danlos syndrome, Gaucher's disease, Stickler's syndrome, joint infection, hemophilia, hemochromatosis, calcium pyrophosphate disposition disease, or neuropathic arthropathy Presence of local skin abnormality at the affected knee joint Any patient who received intra-articular injection within 3 months prior to administration 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: Dose 1<br>SAR113945 low dose | Drug: SAR113945<br>* Pharmaceutical form:injection Route of administration: intra-articular<br>|
| Experimental: Dose 2<br>SAR113945 medium dose | Drug: SAR113945<br>* Pharmaceutical form:injection Route of administration: intra-articular<br>|
| Experimental: Dose 3<br>SAR113945 high dose | Drug: SAR113945<br>* Pharmaceutical form:injection Route of administration: intra-articular<br>|
| Placebo Comparator: Placebo<br>Placebo | 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 |
| --- | --- | --- |
| Number of patients with safety assessments (adverse events, vital signs, 12 lead ECGs and laboratory tests) |  | up to 24 weeks | 
| Examination of skin/soft tissue of injected knee, and knee joint | Examination of skin/soft tissue of injected knee: Any reaction is classified as erythema, edema, pain, hematoma and graded none, mild, moderate or severe. Examination of knee joint of injected knee: Any reaction is classified as effusion/worsening of effusion, warmth and pain. | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameter (AUC) |  | 21 time points up to 24 weeks | 
| Pharmacokinetic parameter (Cmax) |  | 21 time points up to 24 weeks | 
| Pharmacokinetic parameter (tmax) |  | 21 time points up to 24 weeks | 
| Pharmacokinetic parameter (t1/2) |  | 21 time points up to 24 weeks | 
| Pharmacodynamic parameter (WOMAC index) |  | up to 24 weeks | 
| Pharmacodynamic parameter (biomarkers relating to osteoarthritis) |  | up to 24 weeks |