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

Osteoarthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01113333
• Other study ID #: TDU10820
• Secondary ID: 2009-017502-36U1
• Status: Completed
• Phase: Phase 1
• First received: April 23, 2010
• Last updated: March 22, 2011
• Start date: April 2010
• Est. completion date: February 2011

Study information

• Verified date: March 2011
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• placebo
Pharmaceutical form:injection Route of administration: intra-articular
• SAR113945
Pharmaceutical form:injection Route of administration: intra-articular

Locations

Country	Name	City	State
Germany	Sanofi-Aventis Investigational Site Number 276001	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Secondary	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	No
Secondary	Pharmacodynamic parameters (WOMAC Index, biomarkers relating to inflammation and cartilage/bone turnover)		4 weeks	No