Bilateral Knee Osteoarthritis
Conditions
Keywords
Osteoarthritis, Knee, Corticosteroid, Bilateral, Pain, Intra-articular, Injection
Brief summary
This is a randomized, open-label, parallel group study to compare systemic exposure of triamcinolone acetonide following administration into both knees of either FX006 or TAcs.
Detailed description
This is a randomized, open label, parallel group study that will be conducted in male and female patients ≥ 40 years of age with bilateral knee OA. Approximately 24 patients will be randomized to one of two treatment groups (1:1) and treated with IA injections to both knees of either: * extended-release FX006 64 mg total dose (approximately 12 patients) or * immediate-release TAcs 80 mg total dose (approximately 12 patients) Each patient will be screened to confirm the diagnosis of OA and eligibility based on the inclusion/exclusion requirements and will be randomized to treatment on Day 1. Following screening, pharmacokinetics (PK) and safety will be evaluated at 6 out-patient visits scheduled on Study Days 1 \[calendar day of injection\], 2, 8, 15, 29, and 43.
Interventions
DRUGFX006 32 mg
Drug: Extended-release 32 mg FX006 IA injection into each knee (total 64 mg dose)
DRUGTAcs 40 mg
Drug: Immediate-release 40mg TAcs IA injection into each knee (total 80 mg dose)
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
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 * Male or female greater than or equal to 40 years of age * Symptoms consistent with OA in both knees for greater than or equal to 6 months prior to Screening (patient reported is acceptable) * Currently meets ACR Criteria (clinical and radiological) for OA in both knees * Knee pain in both knees for greater than 15 days over the last month (as reported by the patient) * Body mass index (BMI) less than or equal to 40 kg/m2 * Morning serum cortisol result within normal range at Screening (5-23 mcg/dL or 138-635 nmol/dL) * Ambulatory and in good general health * Willing and able to comply with the study procedures and visit schedules and able to follow verbal and written instructions. * Willing to abstain from use of protocol-restricted medications during the study
Exclusion criteria
* Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease * History of infection in either knee joint * Clinical signs and symptoms of active knee infection or crystal disease in either knee within 1 month of Screening * Unstable joint (such as a torn anterior cruciate ligament) in either knee within 12 months of Screening * Presence of surgical hardware or other foreign body in either knee * Surgery or arthroscopy of either knee within 12 months of Screening * IA treatment of any joint with any of the following agents within six (6) months of Screening: any corticosteroid preparation (investigational or marketed, including FX006), any biologic agent (e.g., platelet rich plasma (PRP) injection, stem cells, prolotherapy, amniotic fluid injection; investigational or marketed). * IA treatment in either knee with hyaluronic acid (investigational or marketed) within 6 months of Screening * Parenteral or oral corticosteroids (investigational or marketed) within 3 months of Screening * Inhaled, intranasal or topical corticosteroids (investigational or marketed) within 2 weeks of Screening * Females who are pregnant or nursing or plan to become pregnant during the study; men who plan to conceive during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | 43 days | Plasma drug concentrations (pg/mL) by Time Point across FX006 and TAcs treatment arms in plasma. For the PK analysis and individual concentration vs. time plots, a concentration that is BLOQ is assigned a value of zero if it occurs in a profile before the first measurable concentration. If a BLOQ value occurs after a measurable concentration in a profile and is followed by a value above the lower limit of quantification, then the BLOQ is treated as missing data. If a BLOQ value occurs at the end of the collection interval (after the last quantifiable concentration) it is set to zero. If two BLOQ values occur in succession after Cmax, the profile is deemed to have terminated at the first BLOQ value and any subsequent concentrations are set to zero for PK calculations |
| Incidence of Treatment Emergent Adverse Events | 43 days | Safety analyses were conducted using the safety population. Analyses of adverse events will be performed for those events that are considered treatment emergent, where treatment emergent is defined as any adverse event with onset after the administration of study medication in the first knee through the end of the study or any event that was present at baseline but worsened in intensity through the end of the study. Severity of Adverse events were graded by the Principal Investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The grading went from Grade 1 (Mild) to Grade 5 (Death related to AE). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FX006 64 mg Single 5 mL IA injection into each knee | 12 |
| TAcs IR 80mg Single 5 mL IA injection into each knee | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | FX006 64 mg | TAcs IR 80mg | Total |
|---|---|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 6.45 | 61.6 years STANDARD_DEVIATION 8.17 | 61.7 years STANDARD_DEVIATION 7.2 |
| Body Mass Index (BMI) | 33.31 kg/m^2 STANDARD_DEVIATION 3.669 | 30.35 kg/m^2 STANDARD_DEVIATION 4.955 | 31.83 kg/m^2 STANDARD_DEVIATION 4.524 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 12 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 8 / 12 | 5 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Incidence of Treatment Emergent Adverse Events
Safety analyses were conducted using the safety population. Analyses of adverse events will be performed for those events that are considered treatment emergent, where treatment emergent is defined as any adverse event with onset after the administration of study medication in the first knee through the end of the study or any event that was present at baseline but worsened in intensity through the end of the study. Severity of Adverse events were graded by the Principal Investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The grading went from Grade 1 (Mild) to Grade 5 (Death related to AE).
Time frame: 43 days
Population: All patients who received study drug (injection in at least one knee).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FX006 32 mg | Incidence of Treatment Emergent Adverse Events | Patients with TEAE Grade 2 | 1 participants |
| FX006 32 mg | Incidence of Treatment Emergent Adverse Events | Patients with TEAE Grade 4 | 0 participants |
| FX006 32 mg | Incidence of Treatment Emergent Adverse Events | Patients with TEAE Grade 3 | 1 participants |
| FX006 32 mg | Incidence of Treatment Emergent Adverse Events | Patients with TEAE Grade 5 | 0 participants |
| FX006 32 mg | Incidence of Treatment Emergent Adverse Events | Patients with TEAE Grade 1 | 6 participants |
| TAcs 40 mg | Incidence of Treatment Emergent Adverse Events | Patients with TEAE Grade 5 | 0 participants |
| TAcs 40 mg | Incidence of Treatment Emergent Adverse Events | Patients with TEAE Grade 1 | 3 participants |
| TAcs 40 mg | Incidence of Treatment Emergent Adverse Events | Patients with TEAE Grade 2 | 2 participants |
| TAcs 40 mg | Incidence of Treatment Emergent Adverse Events | Patients with TEAE Grade 3 | 0 participants |
| TAcs 40 mg | Incidence of Treatment Emergent Adverse Events | Patients with TEAE Grade 4 | 0 participants |
Primary
Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma
Plasma drug concentrations (pg/mL) by Time Point across FX006 and TAcs treatment arms in plasma. For the PK analysis and individual concentration vs. time plots, a concentration that is BLOQ is assigned a value of zero if it occurs in a profile before the first measurable concentration. If a BLOQ value occurs after a measurable concentration in a profile and is followed by a value above the lower limit of quantification, then the BLOQ is treated as missing data. If a BLOQ value occurs at the end of the collection interval (after the last quantifiable concentration) it is set to zero. If two BLOQ values occur in succession after Cmax, the profile is deemed to have terminated at the first BLOQ value and any subsequent concentrations are set to zero for PK calculations
Time frame: 43 days
Population: All patients who received 2 IA injections (one in each knee) of study drug, completed scheduled sampling, and had sufficient plasma concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1- Hour 1 | 1801.5 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 2 | 1893.6 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 3 | 1958.1 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 4 | 2013.8 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 5 | 1914.4 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 6 | 1900.2 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 8 | 1928.1 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 10 | 1839.8 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 12 | 1793.9 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 2 - Hour 24 | 1948.8 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 8 | 1397.0 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 15 | 956.2 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 29 | 445.8 pg/mL |
| FX006 32 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 43 | 265.8 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 8 | 450.8 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1- Hour 1 | 4507.9 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 10 | 4948.8 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 2 | 5140.1 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 29 | 334.6 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 3 | 5443.8 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 12 | 4507.8 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 4 | 5454.2 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 15 | 428.7 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 5 | 5338.9 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 2 - Hour 24 | 4185.4 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 6 | 5430.6 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 43 | 241.0 pg/mL |
| TAcs 40 mg | Measure the Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 8 | 5199.0 pg/mL |