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

Study Overview
=================
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).

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

Conditions
-----------------
Osteoarthritis of the Knee

Intervention / Treatment
-----------------
* Drug: FX006 10 mg
* Drug: FX006 40 mg
* Drug: FX006 60 mg
* Drug: TCA IR 40


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FX006 10mg<br>Single 3 mL intra-articular (IA) injection Extended-release formulation | Drug: FX006 10 mg<br>* single 3 mL IA injection<br>|
| Experimental: FX006 40mg<br>Single 3 mL intra-articular (IA) injection Extended-release formulation | Drug: FX006 40 mg<br>* single 3 mL IA injection<br>|
| Experimental: FX006 60 mg<br>Single 3 mL intra-articular (IA) injection Extended-release formulation | Drug: FX006 60 mg<br>* single 3 mL IA injection<br>|
| Active Comparator: TCA IR (40 mg)<br>Single 1 mL intra-articular (IA) injection Immediate-release formulation | Drug: TCA IR 40<br>* single 1 mL IA injection<br>* Other names: Triamcinolone Acetonide Crystalline Suspension (TAcs);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 24-hour Weighted Mean Serum Cortisol | 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 | Days 1-2, Days 14-15 (Week 2) and Days 42-43 (Week 6) | 
| Characterize the Pharmacokinetic Profile of FX006 and TCA IR | Concentrations below the limit of quantification of 50 pg/mL were treated as 0. | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Least square mean difference against TCA IR 40 mg | Baseline to Days 2, 3, 4, 5, 8, 14, 15, 22, 29, 36, 42 and 43 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
osteoarthritis, knee, corticosteroid, intra-articular, injection