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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 September 18, 2014