Osteoarthritis of the Knee
Conditions
Keywords
osteoarthritis, knee, pain, corticosteroid, intra-articular, injection
Brief summary
The purpose of this study was to assess the magnitude and duration of pain relief of a single IA injection of 2 doses (16 and 32 mg) of FX006, an extended-release formulation of TCA, relative to normal saline (placebo control).
Detailed description
This was a double-blind, randomized, parallel group, dose-ranging, single-dose study. The study was conducted in male and female patients ≥40 years of age with OA of the knee. Approximately 300 patients with OA of the knee were randomized, using a centralized randomization procedure, to 1 of 3 treatment groups (1:1:1) and treated with a single IA injection of: * 16 mg FX006, * 32 mg FX006, or * normal saline (placebo). Each patient was evaluated for a total of 24 weeks following a single IA injection. Following screening, safety and efficacy were evaluated at 7 out-patient visits (Days 1 \[Baseline\], Weeks 4, 8, 12, 16, 20, and 24). The study was expected to enroll over approximately 6 to 7 months.
Interventions
DRUGFX006 32 mg
Single 5 mL IA injection
DRUGPlacebo
Single 5 mL IA injection
DRUGFX006 16 mg
Single 5 mL IA injection
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion 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 \>=40 years of age * Has documented diagnosis of OA of the index knee made at least 6 months prior to Screening * Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA * Kellgren-Lawrence (K-L) Grade 2 or 3 in the index knee per Screening X-ray * 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 or clinical signs and symptoms of infection in the index joint * Knee pain that is not clinically attributable to OA of the knee (e.g., radicular low back pain and hip pain that is referred to the knee that could cause misclassification) * Pain in any other area of the lower extremities or back that is equal to or greater than the index knee pain * 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 * Intramuscular (IM) corticosteroids (investigational or marketed) within 3 months of Screening * Oral corticosteroids (investigational or marketed) within 1 month of Screening * Inhaled, intranasal and topical corticosteroids (investigational or marketed) within 2 weeks of Screening * Any other IA investigational drug/biologic within 6 months of Screening * Prior use of FX006 * Women of child-bearing potential not using effective contraception or who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in the Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores for 32 mg FX006 Versus Placebo | Baseline and Week 12 | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no painand 10 indicates pain as bad as you can imagine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 for WOMAC C (Function Subscale) | Baseline and Week 12 | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
| Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC) | Baseline and Week 12 | The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. |
| Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores | Baseline and Weeks 16, 20 and 24 | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function | Baseline and Weeks 4, 8, 16, 20 and 24 (Week 12 data is represented in the secondary outcome measure) | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
| Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Baseline and Weeks 4, 8, 12, 16, 20 and 24 | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
| Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria | Weeks 4, 8 and 12 | Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International. (OMERACT-OARSI) Responders are defined as participants with high improvement in pain or function. |
| Proportion of Patients Experiencing a >20%, 30% and 50% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Week 12 | 12 weeks | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. |
| Time to Onset of Pain Relief | Baseline up to 24 Weeks after administration of study treatment | Time to onset of pain relief in days is defined as the time from administration of study treatment to the first pain assessment showing \>30% improvement from the weekly average daily pain score at baseline. |
| Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC | Baseline and Weeks 4, 8, 16, 20, and 24 (Week 12 data reported in secondary outcome measure) | The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. |
| Change From Baseline to Week 12 for WOMAC C (Function Subscale) | Baseline and Week 12 | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5- point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
| Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC) | Baseline and Week 12 | The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. |
| Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Baseline and Up to Week 24 | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.Weeks 12, 16, 20, and 24 are specified as the primary and secondary endpoints for the 32 mg group and the placebo group |
Countries
Canada, United States
Participant flow
Recruitment details
Patients were screened for study eligibility at 48 study centers in the United States (US) and Canada. Enrollment took approximately 7 months.
Pre-assignment details
Subjects were screened within 21 days of being randomized
Participants by arm
| Arm | Count |
|---|---|
| FX006 16 mg Single intra-articular injection
FX006: Single intra-articular injection | 102 |
| FX006 32 mg Single intra-articular injection
FX006: Single intra-articular injection | 104 |
| Normal Saline Single intra-articular injection
Normal saline: Single intra-articular injection | 100 |
| Total | 306 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 | 1 |
| Overall Study | Lack of Efficacy | 6 | 6 | 5 |
| Overall Study | Lost to Follow-up | 4 | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 1 |
| Overall Study | scheduling conflicts and relocation | 3 | 3 | 6 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 5 |
Baseline characteristics
| Characteristic | FX006 16 mg | FX006 32 mg | Normal Saline | Total |
|---|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 8.34 | 58.7 years STANDARD_DEVIATION 8.06 | 59.7 years STANDARD_DEVIATION 8.23 | 58.8 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 62 Participants | 51 Participants | 61 Participants | 174 Participants |
| Sex: Female, Male Male | 40 Participants | 53 Participants | 39 Participants | 132 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 0 / 104 | 0 / 100 |
| other Total, other adverse events | 14 / 102 | 13 / 104 | 21 / 100 |
| serious Total, serious adverse events | 1 / 102 | 3 / 104 | 0 / 100 |
Outcome results
Primary
Change From Baseline to Week 12 in the Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores for 32 mg FX006 Versus Placebo
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no painand 10 indicates pain as bad as you can imagine.
Time frame: Baseline and Week 12
Population: Randomized patients who received study drug assigned to the FX006 32 mg arm and the placebo arm
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 32 mg | Change From Baseline to Week 12 in the Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores for 32 mg FX006 Versus Placebo | -3.08 units on a scale | Standard Error 0.229 |
| Placebo | Change From Baseline to Week 12 in the Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores for 32 mg FX006 Versus Placebo | -2.50 units on a scale | Standard Error 0.238 |
Comparison: The step-down testing procedure to control for multiplicity would be voided if the primary endpoint is not met and analyses proceeded for exploratory purposes.p-value: 0.082195% CI: [-1.22, 0.07]Logitudinal mixed effects model
Secondary
Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC)
The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.
Time frame: Baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 32 mg | Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC) | 2.6 units on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC) | 2.7 units on a scale | Standard Error 0.14 |
Secondary
Change From Baseline to Week 12 for WOMAC C (Function Subscale)
The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: Baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 32 mg | Change From Baseline to Week 12 for WOMAC C (Function Subscale) | -1.01 units on a scale | Standard Error 0.083 |
| Placebo | Change From Baseline to Week 12 for WOMAC C (Function Subscale) | -0.79 units on a scale | Standard Error 0.087 |
Secondary
Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.
Time frame: Baseline and Weeks 16, 20 and 24
Population: Randomized patients who received study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 32 mg | Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores | Week 16 | -2.83 units on a scale | Standard Error 0.2224 |
| FX006 32 mg | Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores | Week 20 | -2.81 units on a scale | Standard Error 0.233 |
| FX006 32 mg | Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores | Week 24 | -2.51 units on a scale | Standard Error 0.241 |
| Placebo | Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores | Week 16 | -2.46 units on a scale | Standard Error 0.234 |
| Placebo | Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores | Week 20 | -2.34 units on a scale | Standard Error 0.244 |
| Placebo | Change From Baseline to Week 16 and Then Week 20 and Then Week 24 in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores | Week 24 | -2.24 units on a scale | Standard Error 0.252 |
Other Pre-specified
Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain
The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20 and 24
Population: Change from baseline to each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A pain for patients assigned to FX006 16 mg arm was not a pre-specified Secondary Outcome and therefore not reported.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 4 | -1.11 units on a scale | Standard Error 0.08 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 8 | -1.09 units on a scale | Standard Error 0.083 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 12 | -0.98 units on a scale | Standard Error 0.08 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 16 | -0.95 units on a scale | Standard Error 0.083 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 20 | -0.89 units on a scale | Standard Error 0.083 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 24 | -0.91 units on a scale | Standard Error 0.084 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 20 | -0.84 units on a scale | Standard Error 0.086 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 4 | -0.64 units on a scale | Standard Error 0.082 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 16 | -0.80 units on a scale | Standard Error 0.087 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 8 | -0.71 units on a scale | Standard Error 0.087 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 24 | -0.78 units on a scale | Standard Error 0.086 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 12, 16, 20, and 24 in WOMAC-A Pain | Week 12 | -0.81 units on a scale | Standard Error 0.083 |
Other Pre-specified
Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC
The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.
Time frame: Baseline and Weeks 4, 8, 16, 20, and 24 (Week 12 data reported in secondary outcome measure)
Population: Change from baseline to each of Weeks 4, 8, 16, 20, and 24 in PGIC for patients assigned to FX006 16 mg arm was not a pre-specified Secondary Outcome and therefore not reported.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC | Week 8 | 2.4 units on a scale | Standard Error 0.14 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC | Week 20 | 2.9 units on a scale | Standard Error 0.15 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC | Week 16 | 2.8 units on a scale | Standard Error 0.16 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC | Week 24 | 2.7 units on a scale | Standard Error 0.16 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC | Week 4 | 2.2 units on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC | Week 24 | 3.1 units on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC | Week 4 | 3.0 units on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC | Week 8 | 2.8 units on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC | Week 16 | 2.7 units on a scale | Standard Error 0.16 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in PGIC | Week 20 | 2.8 units on a scale | Standard Error 0.16 |
Other Pre-specified
Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function
The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: Baseline and Weeks 4, 8, 16, 20 and 24 (Week 12 data is represented in the secondary outcome measure)
Population: Change from baseline to each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function for patients assigned to FX006 16 mg arm was not a pre-specified Secondary Outcome and therefore not reported
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function | Week 8 | -1.09 units on a scale | Standard Error 0.082 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function | Week 20 | -0.87 units on a scale | Standard Error 0.082 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function | Week 16 | -0.94 units on a scale | Standard Error 0.083 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function | Week 24 | -0.89 units on a scale | Standard Error 0.083 |
| FX006 32 mg | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function | Week 4 | -1.16 units on a scale | Standard Error 0.079 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function | Week 24 | -0.80 units on a scale | Standard Error 0.086 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function | Week 4 | -0.66 units on a scale | Standard Error 0.082 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function | Week 8 | -0.74 units on a scale | Standard Error 0.085 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function | Week 16 | -0.84 units on a scale | Standard Error 0.086 |
| Placebo | Change From Baseline to Each of Weeks 4, 8, 16, 20, and 24 in WOMAC-C-function | Week 20 | -0.84 units on a scale | Standard Error 0.085 |
Other Pre-specified
Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.Weeks 12, 16, 20, and 24 are specified as the primary and secondary endpoints for the 32 mg group and the placebo group
Time frame: Baseline and Up to Week 24
Population: Randomized patients who received study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 7 | -3.14 units on a scale | Standard Error 0.233 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 2 | -2.88 units on a scale | Standard Error 0.218 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 3 | -2.90 units on a scale | Standard Error 0.228 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 4 | -3.05 units on a scale | Standard Error 0.228 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 5 | -3.28 units on a scale | Standard Error 0.222 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 6 | -3.27 units on a scale | Standard Error 0.225 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 1 | -2.04 units on a scale | Standard Error 0.177 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 8 | -3.08 units on a scale | Standard Error 0.237 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 9 | -3.09 units on a scale | Standard Error 0.233 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 10 | -2.88 units on a scale | Standard Error 0.229 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 11 | -2.78 units on a scale | Standard Error 0.234 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 12 | -2.59 units on a scale | Standard Error 0.234 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 13 | -2.68 units on a scale | Standard Error 0.234 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 14 | -2.38 units on a scale | Standard Error 0.235 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 15 | -2.38 units on a scale | Standard Error 0.225 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 16 | -2.30 units on a scale | Standard Error 0.231 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 17 | -2.32 units on a scale | Standard Error 0.237 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 18 | -2.32 units on a scale | Standard Error 0.24 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 19 | -2.27 units on a scale | Standard Error 0.241 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 20 | -2.27 units on a scale | Standard Error 0.241 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 21 | -2.21 units on a scale | Standard Error 0.246 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 22 | -2.41 units on a scale | Standard Error 0.249 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 23 | -2.33 units on a scale | Standard Error 0.258 |
| FX006 32 mg | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 24 | -2.38 units on a scale | Standard Error 0.249 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 22 | -2.53 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 1 | -1.96 units on a scale | Standard Error 0.175 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 13 | -3.12 units on a scale | Standard Error 0.229 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 17 | -2.71 units on a scale | Standard Error 0.229 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 2 | -2.75 units on a scale | Standard Error 0.216 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 11 | -3.18 units on a scale | Standard Error 0.229 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 21 | -2.71 units on a scale | Standard Error 0.237 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 3 | -2.91 units on a scale | Standard Error 0.226 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 14 | -2.83 units on a scale | Standard Error 0.229 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 23 | -2.40 units on a scale | Standard Error 0.249 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 4 | -3.20 units on a scale | Standard Error 0.226 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 10 | -3.17 units on a scale | Standard Error 0.224 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 18 | -2.73 units on a scale | Standard Error 0.232 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 5 | -3.39 units on a scale | Standard Error 0.219 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 15 | -2.91 units on a scale | Standard Error 0.219 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 12 | -3.08 units on a scale | Standard Error 0.229 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 6 | -3.29 units on a scale | Standard Error 0.222 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 9 | -3.24 units on a scale | Standard Error 0.229 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 24 | -2.51 units on a scale | Standard Error 0.241 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 7 | -3.13 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 16 | -2.83 units on a scale | Standard Error 0.224 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 19 | -2.76 units on a scale | Standard Error 0.233 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 8 | -3.04 units on a scale | Standard Error 0.234 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 20 | -2.81 units on a scale | Standard Error 0.233 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 8 | -2.33 units on a scale | Standard Error 0.242 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 9 | -2.39 units on a scale | Standard Error 0.237 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 10 | -2.44 units on a scale | Standard Error 0.233 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 11 | -2.48 units on a scale | Standard Error 0.238 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 20 | -2.34 units on a scale | Standard Error 0.244 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 12 | -2.50 units on a scale | Standard Error 0.238 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 23 | -2.25 units on a scale | Standard Error 0.26 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 13 | -2.43 units on a scale | Standard Error 0.239 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 14 | -2.48 units on a scale | Standard Error 0.239 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 21 | -2.38 units on a scale | Standard Error 0.248 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 15 | -2.44 units on a scale | Standard Error 0.229 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 24 | -2.24 units on a scale | Standard Error 0.252 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 16 | -2.46 units on a scale | Standard Error 0.234 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 1 | -1.24 units on a scale | Standard Error 0.178 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 2 | -1.65 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 17 | -2.41 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 3 | -1.74 units on a scale | Standard Error 0.231 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 22 | -2.30 units on a scale | Standard Error 0.251 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 4 | -1.84 units on a scale | Standard Error 0.232 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 5 | -2.05 units on a scale | Standard Error 0.225 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 18 | -2.34 units on a scale | Standard Error 0.242 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 6 | -2.20 units on a scale | Standard Error 0.229 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 7 | -2.28 units on a scale | Standard Error 0.237 |
| Placebo | Change From Baseline to Each Week in Weekly Mean of the ADP Intensity Scores | Week 19 | -2.28 units on a scale | Standard Error 0.243 |
Other Pre-specified
Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC)
The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.
Time frame: Baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 32 mg | Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC) | 2.5 units on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline to Week 12 for Patient Global Impression of Change (PGIC) | 2.7 units on a scale | Standard Error 0.14 |
Other Pre-specified
Change From Baseline to Week 12 for WOMAC C (Function Subscale)
The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5- point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: Baseline and Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 32 mg | Change From Baseline to Week 12 for WOMAC C (Function Subscale) | -0.83 units on a scale | Standard Error 0.085 |
| Placebo | Change From Baseline to Week 12 for WOMAC C (Function Subscale) | -0.79 units on a scale | Standard Error 0.087 |
Other Pre-specified
Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria
Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International. (OMERACT-OARSI) Responders are defined as participants with high improvement in pain or function.
Time frame: Weeks 4, 8 and 12
Population: Percent of responders according to Outcomes Measures in OMERACT-OARSI strict criteria for patients assigned to FX006 16 mg arm was not a pre-specified Secondary Outcome and therefore not reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FX006 32 mg | Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria | Week 4 | 75 Participants |
| FX006 32 mg | Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria | Week 8 | 73 Participants |
| FX006 32 mg | Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria | Week 12 | 70 Participants |
| Placebo | Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria | Week 4 | 51 Participants |
| Placebo | Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria | Week 8 | 58 Participants |
| Placebo | Percent of Responders According to Outcomes Measures in OMERACT-OARSI Strict Criteria | Week 12 | 57 Participants |
Other Pre-specified
Proportion of Patients Experiencing a >20%, 30% and 50% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Week 12
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.
Time frame: 12 weeks
Other Pre-specified
Time to Onset of Pain Relief
Time to onset of pain relief in days is defined as the time from administration of study treatment to the first pain assessment showing \>30% improvement from the weekly average daily pain score at baseline.
Time frame: Baseline up to 24 Weeks after administration of study treatment
Population: Time to onset of pain relief for patients assigned to FX006 16 mg arm was not a pre-specified Secondary Outcome and therefore not reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FX006 32 mg | Time to Onset of Pain Relief | 4 days |
| Placebo | Time to Onset of Pain Relief | 8 days |