Osteoarthritis of Knee
Conditions
Brief summary
To compare flavocoxid with naproxen for patients with moderate to severe osteoarthritis of the knee.
Detailed description
Efficacy of flavocoxid 500 mg compared with naproxen 500 mg in subjects with moderate-severe osteoarthritis of the knee.
Interventions
DIETARY_SUPPLEMENTflavocoxid
medical food
DRUGNaproxen
antiinflammatory drug
Sponsors
Primus Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Willing and able to read and understand informed consent and questionnaires in English. * Adults of either gender age 35-75 years, in general good health. * Established X-ray diagnosis of osteoarthritis of at least one knee. * Taken NSAID including COX-2 (cyclo-oxygenase-2) inhibitor in full therapeutic dose for at least one month prior to screening. * Able and will to discontinue osteoarthritis medications until flare criteria met. * BMI\</= 45 * Subjects must rate target knee at least 5 out of 10 on discomfort VAS (visual analogue scale) at baseline visit. * Have an increase of at least 15mm on a 100mm pain VAS (visual analogue scale) from screening to baseline visit. * Must use acceptable birth control if female. * Screening fecal occult must be negative. * Able to attend all required visits * Physical Therapy is allowed as long as the type and frequency remains unchanged for the duration of the study.
Exclusion criteria
* Refusal to sign consent. * Inability to attend all clinic visits * Grade 0-1 K-L changes in both knees or grade 4 K-L changes in either knee on standing A/P radiograph * Pregnant or lactating women * History of serious cardio-vascular disease. * Recurrent arrythmias, except paroxysmal tachycardia, cardiomyopathy, myocardial infarct within one year of screening. * History of chronic esophageal, gastric or duodenal disease * History of upper GI bleeding within the past 2 years. * Any GI disorder associated with malabsorption * Any musculo-skeletal or neurological condition that results in pain or gait disturbance that might confound evaluation of target knee. * Uncontrolled Diabetes Mellitus * History of bleeding disorder or concurrent use of coumadin or any agent used to reduce blood clotting or platelet adhesiveness. * Concurrent use of any anti-arthritic medication, including corticosteroids regardless of the reason for use. (low dose aspirin for cardioprotection is allowed) * History of chronic renal disease with creatinine \>2.0 or nephrotic syndrome with 24 hour protein excretion \>1000mg. * Intra-articular injection of any hyaluronic acid preparation in the target knee joint within 4 months of baseline visit. * Intra-articular injection of a corticosteroid in the target knee joint within 2 months of the baseline visit. * BMI\>45 * History of allergic reaction to flavonoid or flavan containing foods or products (example: red wine, colored fruits and vegetable, brazil nuts, tea, natto) * History of allergy to aspirin, naproxen or other NSAID * History of substance abuse including alcohol, or any psychiatric condition that may impair the subject's ability to comply with the study requirements. * Any medical condition that, in the opinion of the investigator, might put the subject at undue risk or might interfere with the subject's ability to participate in the study. * Participation in another clinical trial within 30 days or 7 half lives of the study agent, whichever is longer, of the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Western Ontario and McMaster Universities Arthritis (WOMAC) Composite Score: Percent Change From Baseline to Week 12. | As measured at Baseline and Week 12 | WOMAC is a composite of subscales: pain - 5 questions, stiffness - 2 questions, physical function - 17 questions. Subject answers each question as none=0, slight=1, moderate=2, very=3 and extreme=4 of pain, stiffness and difficulty of function. Scores for each subscale are summed, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. Individual question scores are then summed to form a raw score ranging from 0 (worst) to 96 (best). Raw scores are normalized by multiplying each score by 100/96. This produces a reported WOMAC Score of between 0 (worst) to 100 (best).The higher the score of the units on the scale, the better the outcome. For each individual subject, the percent change from baseline to Week 12 in the WOMAC composite score is calculated as 100 x (week 12 minus baseline)/baseline. The higher the percent change, the better the outcome. The percent changes from baseline to Week 12 are then compared between Flavocoxid and Naproxen. |
Participant flow
Recruitment details
Subjects presented to their providers medical clinic At Screening anti-inflammatory meds discontinued. At Baseline inclusion, exclusion measured At Baseline randomization for eligible participants
Participants by arm
| Arm | Count |
|---|---|
| Flavocoxid 500 mg flavonoid mixture
flavocoxid: medical food | 108 |
| Naproxen 500 mg nonsteroidal anti-inflammatory drug
Naproxen: antiinflammatory drug | 115 |
| Total | 223 |
Baseline characteristics
| Characteristic | Naproxen 500 mg | Flavocoxid 500 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 6 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 105 Participants | 100 Participants | 205 Participants |
| Age, Continuous | 61.08 years | 60.64 years | 60.86 years |
| Region of Enrollment United States | 114 Participants | 106 Participants | 220 Participants |
| Sex: Female, Male Female | 90 Participants | 93 Participants | 183 Participants |
| Sex: Female, Male Male | 24 Participants | 13 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 108 | 0 / 115 |
| other Total, other adverse events | 21 / 108 | 39 / 115 |
| serious Total, serious adverse events | 0 / 108 | 0 / 115 |
Outcome results
Primary
Western Ontario and McMaster Universities Arthritis (WOMAC) Composite Score: Percent Change From Baseline to Week 12.
WOMAC is a composite of subscales: pain - 5 questions, stiffness - 2 questions, physical function - 17 questions. Subject answers each question as none=0, slight=1, moderate=2, very=3 and extreme=4 of pain, stiffness and difficulty of function. Scores for each subscale are summed, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. Individual question scores are then summed to form a raw score ranging from 0 (worst) to 96 (best). Raw scores are normalized by multiplying each score by 100/96. This produces a reported WOMAC Score of between 0 (worst) to 100 (best).The higher the score of the units on the scale, the better the outcome. For each individual subject, the percent change from baseline to Week 12 in the WOMAC composite score is calculated as 100 x (week 12 minus baseline)/baseline. The higher the percent change, the better the outcome. The percent changes from baseline to Week 12 are then compared between Flavocoxid and Naproxen.
Time frame: As measured at Baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naproxen | Western Ontario and McMaster Universities Arthritis (WOMAC) Composite Score: Percent Change From Baseline to Week 12. | 85.75 percentage of change | Standard Deviation 9.83 |
| Flavocoxid 500 mg | Western Ontario and McMaster Universities Arthritis (WOMAC) Composite Score: Percent Change From Baseline to Week 12. | 69.97 percentage of change | Standard Deviation 7.34 |