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

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT01113333
First received: April 23, 2010
Last updated: March 22, 2011
Last verified: March 2011
  Purpose

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.

Condition Intervention Phase
Osteoarthritis
Drug: placebo
Drug: SAR113945
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Standard safety investigations (Physical examinations, 12 lead ECGs, vital signs (Blood pressure, heart rate, body temperature) and laboratory tests (hematology/coagulation, biochemistry, quantitative urinalysis)) [ Time Frame: 4 weeks up to a maximum of 12 weeks ] [ Designated as safety issue: Yes ]
  • Examination of skin/soft tissue of injected knee [ Time Frame: 4 weeks up to a maximum of 12 weeks ] [ Designated as safety issue: Yes ]
    Any reaction is classified as erythema, oedema, pain, papulae, haematoma and graded none, mild, moderate or severe.

  • Examination of knee joint of injected knee [ Time Frame: 4 weeks up to a maximum of 12 weeks ] [ Designated as safety issue: Yes ]
    Any reaction is classified as effusion/worsening of effusion, warm and pain.


Secondary Outcome Measures:
  • Pharmacokinetic parameters for SAR113945 and potential metabolites(s) from plasma concentration (i.e. AUC, Cmax, tmax, t1/2) [ Time Frame: 4 weeks up to a maximum of 16 weeks ] [ Designated as safety issue: No ]
  • Pharmacodynamic parameters (WOMAC Index, biomarkers relating to inflammation and cartilage/bone turnover) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: April 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR113945
SAR113945, single dose according to dose escalation design
Drug: SAR113945

Pharmaceutical form:injection

Route of administration: intra-articular

Placebo Comparator: Placebo
0.9% saline solution, single dose
Drug: placebo

Pharmaceutical form:injection

Route of administration: intra-articular


Detailed 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.
  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01113333

Locations
Germany
Sanofi-Aventis Investigational Site Number 276001
Berlin, Germany, 14050
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Trial Transparency Team, sanofi-aventis
ClinicalTrials.gov Identifier: NCT01113333     History of Changes
Other Study ID Numbers: TDU10820, 2009-017502-36, U1111-1116-5630
Study First Received: April 23, 2010
Last Updated: March 22, 2011
Health Authority: Germany: Ethics Commission

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on April 17, 2014