Pharmacokinetic and Pharmacodynamic Study of FX006 in Patients With Osteoarthritis of the Knee
Primary Purpose
Osteoarthritis of the Knee
Status
Completed
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
FX006 10 mg
FX006 40 mg
FX006 60 mg
TCA IR 40
Sponsored by

About this trial
This is an interventional treatment trial for Osteoarthritis of the Knee focused on measuring osteoarthritis, knee, corticosteroid, intra-articular, injection
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
FX006 10mg
FX006 40mg
FX006 60 mg
TCA IR (40 mg)
Arm Description
Single 3 mL intra-articular (IA) injection Extended-release formulation
Single 3 mL intra-articular (IA) injection Extended-release formulation
Single 3 mL intra-articular (IA) injection Extended-release formulation
Single 1 mL intra-articular (IA) injection Immediate-release formulation
Outcomes
Primary Outcome Measures
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
Characterize the Pharmacokinetic Profile of FX006 and TCA IR
Concentrations below the limit of quantification of 50 pg/mL were treated as 0.
Secondary Outcome Measures
Change From Baseline in 24-hour Urinary Free Cortisol Excretion
Total 24-hour Urinary Free Cortisol Excretion
Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol
Least square mean difference against TCA IR 40 mg
Full Information
NCT ID
NCT01487200
First Posted
December 5, 2011
Last Updated
November 19, 2019
Sponsor
Flexion Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01487200
Brief Title
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
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Flexion Therapeutics, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis of the Knee
Keywords
osteoarthritis, knee, corticosteroid, intra-articular, injection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FX006 10mg
Arm Type
Experimental
Arm Description
Single 3 mL intra-articular (IA) injection Extended-release formulation
Arm Title
FX006 40mg
Arm Type
Experimental
Arm Description
Single 3 mL intra-articular (IA) injection Extended-release formulation
Arm Title
FX006 60 mg
Arm Type
Experimental
Arm Description
Single 3 mL intra-articular (IA) injection Extended-release formulation
Arm Title
TCA IR (40 mg)
Arm Type
Active Comparator
Arm Description
Single 1 mL intra-articular (IA) injection Immediate-release formulation
Intervention Type
Drug
Intervention Name(s)
FX006 10 mg
Intervention Description
single 3 mL IA injection
Intervention Type
Drug
Intervention Name(s)
FX006 40 mg
Intervention Description
single 3 mL IA injection
Intervention Type
Drug
Intervention Name(s)
FX006 60 mg
Intervention Description
single 3 mL IA injection
Intervention Type
Drug
Intervention Name(s)
TCA IR 40
Other Intervention Name(s)
Kenalog®-40, Kenacort-A 40, Triamcinolone Acetonide Crystalline Suspension (TAcs)
Intervention Description
single 1 mL IA injection
Primary Outcome Measure Information:
Title
Change From Baseline in 24-hour Weighted Mean Serum Cortisol
Description
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
Time Frame
Days 1-2, Days 14-15 (Week 2) and Days 42-43 (Week 6)
Title
Characterize the Pharmacokinetic Profile of FX006 and TCA IR
Description
Concentrations below the limit of quantification of 50 pg/mL were treated as 0.
Time Frame
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 Measure Information:
Title
Change From Baseline in 24-hour Urinary Free Cortisol Excretion
Time Frame
Baseline to Days 1-2, Baseline to Days 14-15 (Week 2) and Baseline to Days 42-43 (Week 6)
Title
Total 24-hour Urinary Free Cortisol Excretion
Time Frame
Days 1-2, Days 14-15 (Week 2) and Days 42-43 (Week 6)
Title
Change From Baseline to Each Measured Time Point Post-dose in Morning Serum Cortisol
Description
Least square mean difference against TCA IR 40 mg
Time Frame
Baseline to Days 2, 3, 4, 5, 8, 14, 15, 22, 29, 36, 42 and 43
10. Eligibility
Sex
All
Minimum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neil Bodick, MD
Organizational Affiliation
Flexion Therapeutics
Official's Role
Study Director
Facility Information:
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
City
Perth
State/Province
Western Australia
Country
Australia
12. IPD Sharing Statement
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Pharmacokinetic and Pharmacodynamic Study of FX006 in Patients With Osteoarthritis of the Knee
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