Osteoarthritis of the Knee
Conditions
Keywords
osteoarthritis, knee, pain, corticosteroid, intra-articular, injection
Brief summary
The objectives of this study were to characterize the local extent and duration of exposure of TA from FX006 and TCA IR, characterize the systemic PK of FX006 and TCA IR, and assess the safety and general tolerability of a single 5 mL IA injection of 32 mg FX006 relative to 40 mg of TCA IR in patients with OA of the knee.
Detailed description
This study employed an open-label, single administration design and was conducted in male and female patients ≥40 years of age with OA of the knee. Patients were enrolled sequentially with at least 10 patients per cohort as follows: Cohort A: FX006 32 mg, Final Visit at Week 20 Cohort B: FX006 32 mg, Final Visit at Week 16 Cohort C: FX006 32 mg, Final Visit at Week 12 Cohort D: FX006 32 mg, Final Visit at Week 6 Cohort E: FX006 32 mg, Final Visit at Week 1 Cohort F: TCA IR 40 mg, Final Visit Week 6 Each patient was screened to confirm eligibility and assigned to a cohort on Day 1/baseline. Each patient was evaluated for safety during his/her participation in the study at 6, 12, 16, or 20 weeks following a single IA injection depending on the assigned Cohort, and plasma and synovial fluid was collected for drug concentration measurements. Safety and tolerability was assessed by physical examinations, index knee examinations, vital signs, clinical laboratory evaluations, and adverse events (AEs). No efficacy assessments were employed in this study.
Interventions
DRUGFX006 32 mg
Single 5 mL IA injection
DRUGTCA IR 40
Single 1 mL IA injection
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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 * Symptoms associated with OA of the knee for ≥ 6 months prior to Screening (patient reported is acceptable) * Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA * Index knee pain for \>15 days over the last month (as reported by the patient) * Body mass index (BMI) ≤ 40 kg/m2 * Ambulatory and in good general health
Exclusion criteria
* Fibromyalgia, Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease * History of infection in the index knee joint * Clinical signs and symptoms of active knee infection or crystal disease of the index knee within 1 month of Screening * Presence of surgical hardware or other foreign body in the index knee * Unstable joint 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 * Intravenous or Intramuscular corticosteroids (investigational or marketed) within 3 months of Screening * Oral corticosteroids (investigational or marketed) within 1 month of Screening * Inhaled, intranasal or topical corticosteroids (investigational or marketed) within 2 weeks of Screening * Any other IA investigational drug/biologic use within 6 months of Screening or 5 half-lives (whichever is longer) * Prior use of FX006 * Women of child-bearing potential not using effective contraception or who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid | Up to 20 Weeks | All baseline (pre-treatment) values and all post-baseline values recorded as below LLOQ (\<50 pg/mL) were set to zero. Geometric mean summary statistics were computed on adjusted concentration values. One (1) was added to each concentration value observed. BLQ values for the computation of geometric mean are included in the summary with a value of 1 (0+1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Up to 20 Weeks | All baseline (pre-treatment) values and all post-baseline values that are recorded as below LLOQ were set to zero for analysis and were included in the descriptive mean calculations. Values below LLOQ were not included in geometric mean calculations. |
Other
| Measure | Time frame |
|---|---|
| Plasma Pharmacokinetic Parameters for FX006 and TCA IR | Up to 20 Weeks |
Countries
United States
Participant flow
Recruitment details
Patients were screened for study eligibility at four (4) study centers in the United States (US).
Pre-assignment details
Patients were enrolled sequentially with at least 10 patients per Cohort. Subjects were enrolled within 14 days of Screening.
Participants by arm
| Arm | Count |
|---|---|
| FX006 32 mg Single 5 mL IA injection | 63 |
| TCA IR 40 mg Single 1 mL IA injection | 18 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | FX006 32 mg | TCA IR 40 mg | Total |
|---|---|---|---|
| Age, Continuous | 59.9 years STANDARD_DEVIATION 8.16 | 61.9 years STANDARD_DEVIATION 7.68 | 61 years STANDARD_DEVIATION 8.16 |
| Sex: Female, Male Female | 32 Participants | 13 Participants | 45 Participants |
| Sex: Female, Male Male | 31 Participants | 5 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 18 |
| other Total, other adverse events | 7 / 63 | 2 / 18 |
| serious Total, serious adverse events | 1 / 63 | 0 / 18 |
Outcome results
Primary
Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid
All baseline (pre-treatment) values and all post-baseline values recorded as below LLOQ (\<50 pg/mL) were set to zero. Geometric mean summary statistics were computed on adjusted concentration values. One (1) was added to each concentration value observed. BLQ values for the computation of geometric mean are included in the summary with a value of 1 (0+1).
Time frame: Up to 20 Weeks
Population: All patients who received study drug and had synovial fluid obtained at the Synovial Fluid Visit and assayed for drug concentration levels.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FX006 32 mg | Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid | Baseline (pre-treatment) | 1.0 pg/mL |
| FX006 32 mg | Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid | Week 16 | 1.0 pg/mL |
| FX006 32 mg | Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid | Week 20 | 1.0 pg/mL |
| FX006 32 mg | Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid | Week 1 | 231328.9 pg/mL |
| FX006 32 mg | Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid | Week 6 | 3590.0 pg/mL |
| FX006 32 mg | Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid | Week 12 | 290.6 pg/mL |
| TCA IR 40 mg | Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid | Baseline (pre-treatment) | 1.0 pg/mL |
| TCA IR 40 mg | Synovial Fluid Drug Concentrations (pg/mL) by Time Point Pooled Across FX006 Cohorts and TCA IR in Synovial Fluid | Week 6 | 7.7 pg/mL |
Secondary
Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort
All baseline (pre-treatment) values and all post-baseline values that are recorded as below LLOQ were set to zero for analysis and were included in the descriptive mean calculations. Values below LLOQ were not included in geometric mean calculations.
Time frame: Up to 20 Weeks
Population: All patients who received study drug and had at least one post-baseline plasma sample obtained and assayed for drug concentration levels.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Week 20 | 108.2 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 1 | 670.0 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 6 | 747.1 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 8 | 740.2 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 10 | 720.7 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 12 | 706.6 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Week 1 | 600.9 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Week 6 | 118.6 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Week 12 | 53.7 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Week 16 | 73.8 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 2 - Hour 24 | 836.4 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 2 | 736.5 pg/mL |
| FX006 32 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 4 | 759.5 pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 1 | 6968.8 pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 2 - Hour 24 | 4991.1 pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 2 | 8494.7 pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 10 | 7439.3 pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 4 | 9628.8 pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Week 6 | 149.4 pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 6 | 9314.3 pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 12 | 6678.7 pg/mL |
| TCA IR 40 mg | Plasma Drug Concentrations (pg/mL) by Time Pooled Across FX006 Cohorts and TCA IR 40 mg Cohort | Day 1 - Hour 8 | 8421.3 pg/mL |
Other Pre-specified
Plasma Pharmacokinetic Parameters for FX006 and TCA IR
Time frame: Up to 20 Weeks