Study of FX006 in Patients With Osteoarthritis of the Knee

Study FX006-2011-001 was a multi-center, randomized, double-blind, active comparator,
parallel-group, single-dose study designed to assess the magnitude and duration of pain
relief of three doses (10, 40, and 60 mg) of FX006, an extended-release formulation of TCA,
relative to commercially-available TCA IR.

The general tolerability of a single injection of FX006 also was assessed.

Secondary objectives included exploration of the effect of FX006 on functional improvement,
responder status, time to onset of pain relief, global impressions of change, and consumption
of analgesic medications and evaluation of the PK profile of single injection of the three
dose levels of FX006.

The study was planned to be conducted in up to 224 male and female patients ≥40 years of age
with OA of the knee enrolled at 22 study centers in the US, Australia, and Canada.

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 >=40 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

- Qualifying mean score on the 24-h average pain score (0-10 numeric rating scale)

- Body mass index (BMI) ≤ 40 kg/m2

- Willingness to abstain from use of restricted medications

Main Exclusion Criteria

- Ipsilateral hip OA

- Fibromyalgia, chronic pain syndrome or other concurrent medical or arthritic
conditions which could interfere with the evaluation of the index knee

- 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 and 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

- Active or history of malignancy within the last 5 years, with the exception of
resected basal cell carcinoma, squamous cell carcinoma of the skin, or resected
cervical atypia or carcinoma in situ

- Insulin-dependent diabetes

- Active psychiatric disorder including psychosis and major depressive disorder

- 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