Clinical trial NCT01487200: Pharmacokinetic and Pharmacodynamic Study of FX006 in Patients With Osteoarthritis of the Knee
Official title: A Double-Blind, Randomized, Parallel Group, Active Comparator Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects (HPA Axis) of FX006 in Patients With Osteoarthritis of the Knee
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis of the Knee
Keywords: osteoarthritis
knee
corticosteroid
intra-articular
injection
Lead sponsor: Pacira Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2011-12-07
Enrollment: 24
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Main Inclusion Criteria:

* 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 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)
* 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

Primary outcomes:
measure: Change From Baseline in 24-hour Weighted Mean Serum Cortisol
timeFrame: Days 1-2, Days 14-15 (Week 2) and Days 42-43 (Week 6)
measure: Characterize the Pharmacokinetic Profile of FX006 and TCA IR
timeFrame: 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
Secondary outcomes:
measure: Change From Baseline in 24-hour Urinary Free Cortisol Excretion
timeFrame: Baseline to Days 1-2, Baseline to Days 14-15 (Week 2) and Baseline to Days 42-43 (Week 6)
measure: Total 24-hour Urinary Free Cortisol Excretion
timeFrame: Days 1-2, Days 14-15 (Week 2) and Days 42-43 (Week 6)
measure: Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol
timeFrame: Baseline to Days 2, 3, 4, 5, 8, 14, 15, 22, 29, 36, 42 and 43
Other outcomes:
Locations:
city: Adelaide
country: Australia
state: South Australia
city: Perth
country: Australia
state: Western Australia
Study officials:
affiliation: Flexion Therapeutics
name: Neil Bodick, MD
role: STUDY_DIRECTOR
References: