Pharmacokinetic and Pharmacodynamic Study of FX006 in Patients With Osteoarthritis of the Knee

Phase 2

Completed

Interventions: Drug: FX006 10 mg
Drug: FX006 40 mg
Drug: FX006 60 mg
Drug: TCA IR 40

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

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

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