Clinical trial NCT01113333: Safety, Tolerability and Pharmacokinetics of SAR113945 Following Intra-articular Administration in Patients With Knee Osteoarthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteoarthritis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-04-29
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Standard safety investigations (Physical examinations, 12 lead ECGs, vital signs (Blood pressure, heart rate, body temperature) and laboratory tests (hematology/coagulation, biochemistry, quantitative urinalysis))
timeFrame: 4 weeks up to a maximum of 12 weeks
measure: Examination of skin/soft tissue of injected knee
timeFrame: 4 weeks up to a maximum of 12 weeks
measure: Examination of knee joint of injected knee
timeFrame: 4 weeks up to a maximum of 12 weeks
Secondary outcomes:
measure: Pharmacokinetic parameters for SAR113945 and potential metabolites(s) from plasma concentration (i.e. AUC, Cmax, tmax, t1/2)
timeFrame: 4 weeks up to a maximum of 16 weeks
measure: Pharmacodynamic parameters (WOMAC Index, biomarkers relating to inflammation and cartilage/bone turnover)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Sanofi-Aventis Investigational Site Number 276001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: