Osteoarthritis of the Hip, Osteoarthritis of the Shoulder
Conditions
Keywords
Osteoarthritis, Shoulder, Hip, Pain, Intra-articular, Injection, Corticosteroid
Brief summary
This is an open-label study to compare systemic exposure to triamcinolone acetonide following a dose of extended-release FX006 or immediate-release TAcs (triamcinolone acetonide suspension) in patients with osteoarthritis of the shoulder (glenohumeral joint) or hip
Detailed description
This is a randomized, open-label, single dose study that will be conducted in male and female patients ≥40 years of age with OA of either the shoulder or the hip. Approximately 24 patients with OA of the shoulder and approximately 24 patients with OA of the hip will be randomized to one of two treatment groups (1:1) and treated with a single IA injection of either: * 32 mg FX006 (approximately 12 patients per joint) or * 40 mg TAcs (approximately 12 patients per joint) Each patient will be screened to confirm the diagnosis of OA of either the shoulder or hip and eligibility based on the other inclusion/exclusion requirements and will be randomized to treatment on Day 1. Each patient will be evaluated for a total of 12 weeks following the IA injection. Following screening, sampling for pharmacokinetics (PK) and safety will be completed at 10 out-patient visits scheduled on Study Days 1 \[calendar day of injection\], 2, 3, 5, 8, 15, 22, 29, 57, and 85.
Interventions
DRUGFX006 32 mg
Extended-release 32 mg FX006 IA injection
DRUGTAcs 40 mg
Immediate-release 40mg TAcs IA injection
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 * Body mass index (BMI) less than or equal to 40 kg/m2 * 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 treatments from Screening through End-of-Study visit * Symptoms consistent with OA of the index joint for ≥ 6 months prior to Screening (patient reported is acceptable) * Pain in the index joint for greater than15 days over the last month (as reported by the patient) * For Shoulder OA patients: Radiologic findings of OA of the index shoulder meeting the Samilson-Prieto (S-P) Classification Grades 2 or 3 * For Hip OA patients: ACR Criteria (clinical and radiological) for OA of the index hip
Exclusion criteria
* Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease * History of infection in the index joint * Clinical findings consistent with active infection or crystal disease in the index joint within 1 month of Screening * History of fracture in the index limb within 12 months of Screening, or fracture with sequelae at any time * Planned or anticipated surgery of the index joint during the study period * Index joint instability or history of acute dislocation within 12 months of Screening * If shoulder is the index joint, history of full or partial rotator cuff tear or significantly compromised rotator cuff function that, in the opinion for the Investigator, increases the difficulty or risk of IA injection * Presence of surgical hardware or other foreign body in the index joint * Surgery or arthroscopy of the index joint within 12 months of Screening * IA treatment of any joint with any of the following agents within 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 of the index joint 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 |
|---|---|---|
| Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | 12 Weeks | Characterize the Pharmacokinetic Profile of FX006 and TCA IR \[Time Frame: Day 1 (pre-treatment,1, 2, 3, 4, 5, 6, 8,10, and 12 hrs. post-dose) and Days 2, 3, 5, 8, 15, 22, 29, 57,and 85\] 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 |
| Total Number of Treatment Emergent Adverse Events | 12 Weeks | Analyses of adverse events (AE) were performed for events considered treatment-emergent (TE). TE was defined as any AE with onset after administration of the 1st dose of study drug or any event present at baseline but worsened in intensity through the study. Severity was graded by the PI using the Common Terminology Criteria for AEs Version 4.0. Grading went from Grade 1 (Mild) to Grade 5 (Death Related to AE). |
Countries
United States
Participant flow
Recruitment details
The recruitment period for this study was from December 2017 to July 2018. The patients were enrolled at medical clinics.
Participants by arm
| Arm | Count |
|---|---|
| FX006 32 mg Shoulder Single intra-articular (IA) injection of FX006 32 mg in the Shoulder
FX006 32 mg: Extended-release 32 mg FX006 IA injection | 12 |
| TAcs 40 mg Shoulder Single intra-articular (IA) injection of TAcs 40 mg in the Shoulder
TAcs 40 mg: Immediate-release 40mg TAcs IA injection | 13 |
| FX006 32 mg Hip Single intra-articular (IA) injection of FX006 32 mg in the Hip
FX006 32 mg: Extended-release 32 mg FX006 IA injection | 15 |
| TAcs 40 mg Hip Single intra-articular (IA) injection of TAcs 40 mg in the Hip
TAcs 40 mg: Immediate-release 40mg TAcs IA injection | 15 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | FX006 32 mg Shoulder | TAcs 40 mg Shoulder | FX006 32 mg Hip | TAcs 40 mg Hip | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.2 years STANDARD_DEVIATION 11.39 | 61.9 years STANDARD_DEVIATION 8.1 | 58.1 years STANDARD_DEVIATION 7.6 | 60.1 years STANDARD_DEVIATION 7.09 | 60.7 years STANDARD_DEVIATION 8.53 |
| Body Mass Index (BMI) | 28.9 kg/mg^2 STANDARD_DEVIATION 5.98 | 30.7 kg/mg^2 STANDARD_DEVIATION 3.59 | 29.3 kg/mg^2 STANDARD_DEVIATION 3.49 | 31.0 kg/mg^2 STANDARD_DEVIATION 4.4 | 30.01 kg/mg^2 STANDARD_DEVIATION 4.367 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 13 Participants | 14 Participants | 14 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 5 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 11 Participants | 8 Participants | 9 Participants | 38 Participants |
| Region of Enrollment United States | 12 participants | 13 participants | 15 participants | 15 participants | 55 participants |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 8 Participants | 5 Participants | 28 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 7 Participants | 10 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 4 / 12 | 3 / 13 | 4 / 15 | 7 / 15 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Concentration of Triamcinolone Acetonide (TA) in Blood Plasma
Characterize the Pharmacokinetic Profile of FX006 and TCA IR \[Time Frame: Day 1 (pre-treatment,1, 2, 3, 4, 5, 6, 8,10, and 12 hrs. post-dose) and Days 2, 3, 5, 8, 15, 22, 29, 57,and 85\] 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: 12 Weeks
Population: All patients in the Safety population who received study drug, completed scheduled sampling and had sufficient plasma concentration data. 50 of 55 patients were included. Four unique patients for whom hip was the index joint were excluded due to IP administration deviations. One of the four was also found to be enrolled at 2 separate study centers.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 2 - Hour 24 | 943.4 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 12 | 903.8 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 6 | 1052.8 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 85 | 100.1 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 10 | 951.4 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 8 | 1016.2 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 29 | 201.0 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 22 | 268.3 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 3 | 1140.0 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 1 | 1061.8 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 15 | 397.6 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 8 | 678.1 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 4 | 1142.4 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 57 | 151.8 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 5 | 754.6 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 3 | 903.4 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 5 | 1093.8 pg/mL |
| FX006 32 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 2 | 1117.6 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 3 | 1501.8 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 1 | 1104.1 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 2 | 1344.8 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 4 | 1594.1 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 5 | 1662.7 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 6 | 1689.6 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 8 | 1668.3 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 10 | 1506.3 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 12 | 1531.3 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 2 - Hour 24 | 1467.0 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 3 | 1413.1 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 5 | 1038.2 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 8 | 857.8 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 15 | 722.7 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 22 | 476.7 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 29 | 418.7 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 57 | 200 pg/mL |
| TAcs 40 mg Shoulder | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 85 | 131.4 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 5 | 792.9 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 2 - Hour 24 | 791.0 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 3 | 682.1 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 4 | 776.1 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 85 | 112.0 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 5 | 562.4 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 57 | 225.1 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 8 | 472.3 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 3 | 748.0 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 15 | 382.6 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 1 | 681.8 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 22 | 235.0 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 2 | 752.2 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 8 | 705.0 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 6 | 743.5 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 10 | 698.2 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 29 | 256.3 pg/mL |
| FX006 32 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 12 | 675.1 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 8 | 4102.3 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 29 | 281.8 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 15 | 444.7 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 2 - Hour 24 | 3218.8 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 4 | 4557.8 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 1 | 3862.3 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 2 | 4052.4 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 3 | 1723.6 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 5 | 4672.6 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 85 | 92.5 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 22 | 331.6 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 5 | 897.3 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 3 | 4519.3 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 6 | 4469.8 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 12 | 3276.2 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 8 | 525.3 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day 1 - Hour 10 | 3615.6 pg/mL |
| TAcs 40 mg Hip | Concentration of Triamcinolone Acetonide (TA) in Blood Plasma | Day - 57 | 133.1 pg/mL |
Primary
Total Number of Treatment Emergent Adverse Events
Analyses of adverse events (AE) were performed for events considered treatment-emergent (TE). TE was defined as any AE with onset after administration of the 1st dose of study drug or any event present at baseline but worsened in intensity through the study. Severity was graded by the PI using the Common Terminology Criteria for AEs Version 4.0. Grading went from Grade 1 (Mild) to Grade 5 (Death Related to AE).
Time frame: 12 Weeks
Population: All patients randomized to receive either FX006 or TAcs in the hip or shoulder.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FX006 32 mg Shoulder | Total Number of Treatment Emergent Adverse Events | 10 Events |
| TAcs 40 mg Shoulder | Total Number of Treatment Emergent Adverse Events | 7 Events |
| FX006 32 mg Hip | Total Number of Treatment Emergent Adverse Events | 8 Events |
| TAcs 40 mg Hip | Total Number of Treatment Emergent Adverse Events | 17 Events |