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

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

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.

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.

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.