Osteoarthritis of the Knee
Conditions
Keywords
osteoarthritis, knee, corticosteroids, triamcinolone acetonide, synovial fluid
Brief summary
The purpose of this study was to characterize the local duration of exposure of TCA for 2 doses of FX006 relative to 40 mg of TCA IR in patients with OA of the knee.
Detailed description
This study was an open-label, single administration design, conducted in male and female patients ≥40 years of age with OA of the knee. Patients were enrolled sequentially with 8 patients per cohort, as follows: Cohort A: FX006 40 mg, Final Visit at Week 20 Cohort B: FX006 40 mg, Final Visit at Week 16 Cohort C: FX006 10 mg, Final Visit at Week 12 Cohort D: FX006 40 mg, Final Visit at Week 12 Cohort E: Triamcinolone acetonide immediate-release (TCA IR) 40 mg, Final Visit Week 12 Each patient was evaluated for up to 12, 16, or 20 weeks following a single IA injection depending on the assigned cohort. Following the screening visit, safety was evaluated at 3 out-patient visits and synovial fluid was collected at Day 1 for baseline measurements and the Final Visit for drug concentration measurements.
Interventions
DRUGFX006 10 mg
Extended-release formulation
DRUGFX006 40 mg
Extended-release formulation
DRUGTCA IR 40 mg
Immediate-release formulation
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Written consent to participate in the study * Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions * Has documented diagnosis of OA of the index knee made at least 6 months prior to Screening * Currently meets American Collage of Rheumatology Criteria (clinical and radiological) for OA * Index knee pain for \>15 days over the last month * Body mass index (BMI) ≤ 40 kg/m2 * Ambulatory and in good general health Key
Exclusion criteria
* History of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis or amyloidosis * History of arthritides due to crystals (e.g., gout, pseudogout) * History of infection in the index joint * Clinical signs and symptoms of active knee infection or crystal disease of the index knee * Presence of surgical hardware or other foreign body in the index knee * Unstable joint (such as a torn anterior cruciate ligament) within 12 months of Screening * IA corticosteroid (investigational or marketed) in any joint within 6 months of Screening * IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening * Oral corticosteroids (investigational or marketed) within 1 month of Screening * Inhaled, intranasal and topical corticosteroids (investigational or marketed) within 2 weeks of Screening * Any other IA investigational drug/biologic within 6 months of Screening * Prior use of FX006 * Prior arthroscopic or open surgery of the index knee within 12 months of Screening * Planned/anticipated surgery of the index knee during the study period * Active or history of malignancy within the last 5 years, with the exception of resected basal cell carcinoma, squamous cell carcinoma of the skin, or resected cervical atypia or carcinoma in situ
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Triamcinolone Acetonide in Synovial Fluid | 12 to 20 weeks | Analyses of synovial fluid drug concentrations were performed using the Synovial Fluid Drug Concentration Population. Values recorded as lower limit of quantification (LLOQ) (\< 50 pg/mL) were counted as half the value below limit of quantification (BLQ). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Drug Concentrations by Time | Weeks 6, 12, 16 and 20 | Plasma Drug Concentration Population. Analyses of plasma drug concentrations were performed using the Plasma Drug Concentration Population. Values recorded as lower limit of quantification (LLOQ) (\< 10 pg/mL) were counted as half the value below limit of quantification (BLQ). |
Countries
United States
Participant flow
Recruitment details
This study took place at 3 centers across the United States. Enrollment took approximately 2 months.
Pre-assignment details
Subjects were screened for eligibility within 14 days of being enrolled
Participants by arm
| Arm | Count |
|---|---|
| FX006 10 mg Single 3 mL IA injection | 10 |
| FX006 40 mg Single 3 mL IA injection | 30 |
| TCA IR 40 mg Single 1 mL IA injection | 10 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | FX006 10 mg | FX006 40 mg | TCA IR 40 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 61.5 years | 62.8 years | 61.6 years | 62.15 years |
| Sex: Female, Male Female | 7 Participants | 20 Participants | 7 Participants | 34 Participants |
| Sex: Female, Male Male | 3 Participants | 10 Participants | 3 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 30 | 0 / 10 |
| other Total, other adverse events | 5 / 10 | 5 / 30 | 4 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 30 | 2 / 10 |
Outcome results
Primary
Concentration of Triamcinolone Acetonide in Synovial Fluid
Analyses of synovial fluid drug concentrations were performed using the Synovial Fluid Drug Concentration Population. Values recorded as lower limit of quantification (LLOQ) (\< 50 pg/mL) were counted as half the value below limit of quantification (BLQ).
Time frame: 12 to 20 weeks
Population: All patients who received study drug and had synovial fluid obtained at the Final Visit were included in the Synovial Fluid Drug Concentration Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FX006 10 mg | Concentration of Triamcinolone Acetonide in Synovial Fluid | Week 16 | NA pg/mL |
| FX006 10 mg | Concentration of Triamcinolone Acetonide in Synovial Fluid | Week 12 | 477.5 pg/mL |
| FX006 10 mg | Concentration of Triamcinolone Acetonide in Synovial Fluid | Week 20 | NA pg/mL |
| FX006 40 mg | Concentration of Triamcinolone Acetonide in Synovial Fluid | Week 16 | 224.3 pg/mL |
| FX006 40 mg | Concentration of Triamcinolone Acetonide in Synovial Fluid | Week 12 | 923.7 pg/mL |
| FX006 40 mg | Concentration of Triamcinolone Acetonide in Synovial Fluid | Week 20 | 33.3 pg/mL |
| TCA IR 40 mg | Concentration of Triamcinolone Acetonide in Synovial Fluid | Week 12 | 250.1 pg/mL |
| TCA IR 40 mg | Concentration of Triamcinolone Acetonide in Synovial Fluid | Week 20 | NA pg/mL |
| TCA IR 40 mg | Concentration of Triamcinolone Acetonide in Synovial Fluid | Week 16 | NA pg/mL |
Secondary
Plasma Drug Concentrations by Time
Plasma Drug Concentration Population. Analyses of plasma drug concentrations were performed using the Plasma Drug Concentration Population. Values recorded as lower limit of quantification (LLOQ) (\< 10 pg/mL) were counted as half the value below limit of quantification (BLQ).
Time frame: Weeks 6, 12, 16 and 20
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FX006 10 mg | Plasma Drug Concentrations by Time | Week 6 | 26.5 pg/mL |
| FX006 10 mg | Plasma Drug Concentrations by Time | Week 12 | 6.6 pg/mL |
| FX006 10 mg | Plasma Drug Concentrations by Time | Week 16 | NA pg/mL |
| FX006 10 mg | Plasma Drug Concentrations by Time | Week 20 | NA pg/mL |
| FX006 40 mg | Plasma Drug Concentrations by Time | Week 20 | 10.1 pg/mL |
| FX006 40 mg | Plasma Drug Concentrations by Time | Week 6 | 100.1 pg/mL |
| FX006 40 mg | Plasma Drug Concentrations by Time | Week 16 | 26.4 pg/mL |
| FX006 40 mg | Plasma Drug Concentrations by Time | Week 12 | 8.9 pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations by Time | Week 20 | NA pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations by Time | Week 12 | 9.4 pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations by Time | Week 16 | NA pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations by Time | Week 6 | 21.1 pg/mL |