Pharmacokinetic and Pharmacodynamic Study of FX006 in Patients With Osteoarthritis of the Knee
- Conditions
- Osteoarthritis of the Knee
- Interventions
- Drug: FX006 10 mgDrug: FX006 40 mgDrug: FX006 60 mgDrug: TCA IR 40
- Registration Number
- NCT01487200
- Lead Sponsor
- Pacira Pharmaceuticals, Inc
- Brief Summary
The purpose of this study was to evaluate the safety, pharmacokinetics and pharmacodynamics of FX006 in patients with osteoarthritis of the knee.
- Detailed Description
This study was a double-blind, randomized, parallel-group, active comparator design. The study was conducted in male and female patients ≥35 years of age with symptomatic OA of the knee.
Twenty-four (24) patients with knee OA were randomized (1:1:1:1) and treated with a single IA injection of either 10, 40, or 60 mg of FX006 or 40 mg of TCA IR.
Each patient was evaluated for a total of 6 weeks following a single IA injection. Following screening, safety, PK and pharmacodynamics (PD) were evaluated during one (1) 48-hour in-patient period (Day -1 to Day 2), two (2) 24-hour in-patient periods (Day 14-15 and Day 42-43) and seven (7) out-patient visits (Days 3, 4, 5, 8, 22, 29 and 36).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
- Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions
- Male or female >=35 years of age
- Diagnosis of unilateral or bilateral OA of the knee for at least 6 months prior to Screening with confirmation of OA according to American College of Rheumatology Criteria for Classification of Idiopathic OA of the Knee (clinical and radiological) based on an X-ray performed within 6 months prior to Screening or during the Screening period
- Body mass index (BMI) ≤ 40 kg/m2
- Willingness to abstain from use of the protocol-specified restricted medications
Main
- 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)
- IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening
- IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening
- Oral, inhaled or intranasal corticosteroids (investigational or marketed) within 1 month of Screening
- 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
- History of or active malignancy, with the exception of resected basal cell carcinoma, squamous cell carcinoma of the skin, or resected cervical atypia or carcinoma in situ within 5 years
- Insulin-dependent diabetes
- History of or active Cushing's syndrome
- Any other clinically significant acute or chronic medical conditions (e.g., uncontrolled diabetes)
- Skin breakdown at the knee where the injection would take place
- Women of child-bearing potential not using effective contraception or who are pregnant or nursing
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FX006 10mg FX006 10 mg Single 3 mL intra-articular (IA) injection Extended-release formulation FX006 40mg FX006 40 mg Single 3 mL intra-articular (IA) injection Extended-release formulation FX006 60 mg FX006 60 mg Single 3 mL intra-articular (IA) injection Extended-release formulation TCA IR (40 mg) TCA IR 40 Single 1 mL intra-articular (IA) injection Immediate-release formulation
- Primary Outcome Measures
Name Time Method Change From Baseline in 24-hour Weighted Mean Serum Cortisol Days 1-2, Days 14-15 (Week 2) and Days 42-43 (Week 6) The primary pharmacodynamic endpoint was change from baseline (pre-dose) to Day 1-2, Day 14-15 (Week 2) and Day 42-43 (Week 6) in 24-hour weighted mean serum cortisol. This is defined as AUC over the 0-24 hour measurement period divided by 24
Characterize the Pharmacokinetic Profile of FX006 and TCA IR Day 1 (1, 2, 4, 6, 8, 12 and 24 hours post dose) and Days 3, 4, 5, 8, 15, 22, 29, 36 and 43 Concentrations below the limit of quantification of 50 pg/mL were treated as 0.
- Secondary Outcome Measures
Name Time Method Change From Baseline in 24-hour Urinary Free Cortisol Excretion Baseline to Days 1-2, Baseline to Days 14-15 (Week 2) and Baseline to Days 42-43 (Week 6) Total 24-hour Urinary Free Cortisol Excretion Days 1-2, Days 14-15 (Week 2) and Days 42-43 (Week 6) Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol Baseline to Days 2, 3, 4, 5, 8, 14, 15, 22, 29, 36, 42 and 43 Least square mean difference against TCA IR 40 mg
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