Study to Compare Exposure of TA Following Administration of FX006 or TAcs in Patients With OA of the Shoulder or Hip

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Open-label Study Comparing the Systemic Exposure to Triamcinolone Acetonide Following a Single Intra-articular Dose of Extended-release FX006 or Immediate-release TAcs (Triamcinolone Acetonide Suspension) in Patients With Osteoarthritis of the Shoulder (Glenohumeral Joint) or Hip

Conditions
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Osteoarthritis of the Shoulder, Osteoarthritis of the Hip

Intervention / Treatment
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* Drug: FX006 32 mg
* Drug: TAcs 40 mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FX006 32 mg<br>Single intra-articular (IA) injection of FX006 32 mg | Drug: FX006 32 mg<br>* Extended-release 32 mg FX006 IA injection<br>* Other names: Zilretta;|
| Active Comparator: TAcs 40 mg<br>Single intra-articular (IA) injection of TAcs 40 mg | Drug: TAcs 40 mg<br>* Immediate-release 40mg TAcs IA injection<br>* Other names: TCA-IR 40;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 Weeks | 
| 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). | 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Shoulder, Hip, Pain, Intra-articular, Injection, Corticosteroid