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

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

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

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: SAR113945; Drug: placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka-Shi, Japan, 532-0003
    • Investigational Site Number 392001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; Pharmaceutical form:injection Route of administration: intra-articular
Experimental: Dose 1; SAR113945 low dose	Drug: SAR113945; Pharmaceutical form:injection Route of administration: intra-articular
Experimental: Dose 2; SAR113945 medium dose	Drug: SAR113945; Pharmaceutical form:injection Route of administration: intra-articular
Experimental: Dose 3; SAR113945 high dose	Drug: SAR113945; Pharmaceutical form:injection Route of administration: intra-articular

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: January 6, 2012
• First Submitted That Met QC Criteria: January 12, 2012
• First Posted (Estimate): January 18, 2012

Study Record Updates

• Last Update Posted (Estimate): October 1, 2012
• Last Update Submitted That Met QC Criteria: September 28, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: TDU11333; U1111-1121-4499 (Other Identifier: UTN)