Osteoarthritis of the Knee
Conditions
Keywords
Osteoarthritis, Arthritis, NSAIDs, Topical NSAID, Diclofenac, PENNSAID
Brief summary
Osteoarthritis (OA) is the most common form of arthritis. It can cause pain, swelling, and reduced motion in the joints. That can reduce quality of life. OA can occur in any joint, but usually affects the hands, knees, hips or spine. The purpose of this study is to find out if doctors might be able to use 2% PENNSAID gel to treat OA in the knee.
Interventions
DRUGPENNSAID Gel
2 mL applied to the front, back and sides of the knee twice a day (morning and night) for 4 weeks
DRUGVehicle
2 mL applied to the front, back and sides of the knee twice a day (morning and night) for 4 weeks
Sponsors
Mallinckrodt
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 85 Years
Healthy volunteers
No
Inclusion criteria
1. Primary osteoarthritis of the knee 2. Radiologic evidence of OA of the knee 3. On stable pain therapy with an oral or topical NSAID or acetaminophen 4. Experience a moderate flare of pain following washout of stable pain therapy 5. Able to read and understand English or Spanish to answer pain assessment questions without any explanation 6. If female, surgically sterile or non-pregnant 7. Except for OA, in reasonably good general health 8. Written informed consent
Exclusion criteria
1. Secondary OA of the study knee 2. History of pseudo gout or inflammatory flare-ups 3. Participation would conflict with contraindications, warnings or precautions as stated in the prescribing information for oral or topical diclofenac 4. Severe, uncontrolled cardiac, renal, hepatic, or other systemic disease 5. Any malignancy within the previous 3 years, except local therapy for superficial skin cancer not on the study knee 6. Known sensitivity to the use of oral or topical diclofenac, aspirin \[acetylsalicylic acid (ASA)\] or any other NSAID, dimethyl sulfoxide (DMSO), or ethanol 7. Ongoing abnormality that could confound interpretation of the safety results (eg, anemia, unresponsive gastrointestinal \[GI\] reflux, etc.) 8. Documented gastroduodenal ulcer or any GI bleeding (except hemorrhoidal) within the last 6 months 9. Uncontrolled diabetes 10. Screening laboratory test results of serum creatinine ≥ 1.5 times upper limit of normal; aspartate aminotransferase (AST), alanine aminotransferase (ALT), or gamma-glutamyltransferase (GGT) ≥ 3 times upper limit of normal; and hemoglobin less than or equal to lower limit of normal 11. Documented alcohol or drug abuse within 1 year 12. If female, breast-feeding 13. Major surgery or previous damage to the study knee at any time, or minor knee surgery to the study knee within 1 year 14. Requires oral or intra-muscular corticosteroids, or received an intra articular corticosteroid injection into the study knee within the past 90 days, or into any other joint within the past 30 days, or currently applying topical corticosteroids onto the study knee 15. Received intra-articular viscosupplementation (eg, hylan G-F 20 \[Synvisc®\]) in the study knee in the past 6 months 16. On prior stable therapy (ie, more than 3 days per week for the previous month) with an opioid analgesic prior to the screening visit will be excluded. 17. Recently started taking a sedative hypnotic medication for insomnia 18. Taking anti-depressants 19. Not willing to discontinue prohibited medications/therapies 20. Cannot tolerate acetaminophen 21. Re-entering study after dropping out or withdrawn from study 22. Used another investigational drug within the previous 30 days 23. On or currently applying for disability benefits on the basis of knee OA 24. History of fibromyalgia 25. Other painful or disabling conditions affecting the knee or leg, or disabling condition of the hands (used to apply the study drug) 26. Skin disorder with current involvement on the hands (used to apply the study drug) or the knee(s) (application site) 27. Referred to an orthopedic surgeon for consideration of, or been advised to have, knee replacement or knee reconstruction surgery 28. Radiologic evidence of OA of the knee advanced to the point that all cartilage has been eroded (ie, bone on bone) 29. Recently started using a cane within the past 30 days 30. History of chronic headaches that may require more than occasional use of rescue medication for headaches
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain When Walking On A Flat Surface | at Baseline | Participants rate their pain intensity when walking on a flat surface as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented. |
| Pain When Going Up Or Down Stairs | at Baseline | Participants rate their pain intensity when going up or down stairs as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented. |
| Pain At Night While In Bed | at Baseline | Participants rate their pain intensity at night while in bed as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented. |
| Pain While Sitting Or Lying Down | at Baseline | Participants rate their pain intensity while sitting or lying down as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented. |
| Pain While Standing | at Baseline | Participants rate their pain intensity while standing as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented. |
Countries
United States
Participant flow
Pre-assignment details
One person who failed screening was randomized in error, but did not receive study drug.
Participants by arm
| Arm | Count |
|---|---|
| PENNSAID Gel Diclofenac sodium 2.0% w/w | 130 |
| Vehicle The complete carrier containing ingredients at the same concentrations as experimental arm without diclofenac sodium | 129 |
| Total | 259 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Medical procedure | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Randomized in error did not participate | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 4 |
Baseline characteristics
| Characteristic | PENNSAID Gel | Vehicle | Total |
|---|---|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 9.23 | 61.9 years STANDARD_DEVIATION 9.07 | 61.1 years STANDARD_DEVIATION 9.17 |
| Region of Enrollment United States | 130 participants | 129 participants | 259 participants |
| Sex: Female, Male Female | 84 Participants | 90 Participants | 174 Participants |
| Sex: Female, Male Male | 46 Participants | 39 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 130 | 0 / 129 |
| other Total, other adverse events | 45 / 130 | 59 / 129 |
| serious Total, serious adverse events | 0 / 130 | 0 / 129 |
Outcome results
Primary
Pain At Night While In Bed
Participants rate their pain intensity at night while in bed as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.
Time frame: at Week 4
Population: mITT population with non-missing data at Week 4
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PENNSAID Gel | Pain At Night While In Bed | Mild | 45 Participants |
| PENNSAID Gel | Pain At Night While In Bed | Severe | 5 Participants |
| PENNSAID Gel | Pain At Night While In Bed | Moderate | 34 Participants |
| PENNSAID Gel | Pain At Night While In Bed | Extreme | 2 Participants |
| PENNSAID Gel | Pain At Night While In Bed | None | 37 Participants |
| Vehicle | Pain At Night While In Bed | Extreme | 0 Participants |
| Vehicle | Pain At Night While In Bed | None | 30 Participants |
| Vehicle | Pain At Night While In Bed | Mild | 45 Participants |
| Vehicle | Pain At Night While In Bed | Moderate | 35 Participants |
| Vehicle | Pain At Night While In Bed | Severe | 8 Participants |
Primary
Pain At Night While In Bed
Participants rate their pain intensity at night while in bed as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.
Time frame: at Baseline
Population: mITT population with non-missing data at Baseline
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PENNSAID Gel | Pain At Night While In Bed | None | 5 Participants |
| PENNSAID Gel | Pain At Night While In Bed | Severe | 32 Participants |
| PENNSAID Gel | Pain At Night While In Bed | Moderate | 60 Participants |
| PENNSAID Gel | Pain At Night While In Bed | Extreme | 9 Participants |
| PENNSAID Gel | Pain At Night While In Bed | Mild | 23 Participants |
| Vehicle | Pain At Night While In Bed | Extreme | 14 Participants |
| Vehicle | Pain At Night While In Bed | Mild | 26 Participants |
| Vehicle | Pain At Night While In Bed | None | 6 Participants |
| Vehicle | Pain At Night While In Bed | Moderate | 50 Participants |
| Vehicle | Pain At Night While In Bed | Severe | 33 Participants |
Primary
Pain When Going Up Or Down Stairs
Participants rate their pain intensity when going up or down stairs as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.
Time frame: at Week 4
Population: mITT population with non-missing data at Week 4
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PENNSAID Gel | Pain When Going Up Or Down Stairs | Mild | 34 Participants |
| PENNSAID Gel | Pain When Going Up Or Down Stairs | Severe | 29 Participants |
| PENNSAID Gel | Pain When Going Up Or Down Stairs | Moderate | 51 Participants |
| PENNSAID Gel | Pain When Going Up Or Down Stairs | Extreme | 5 Participants |
| PENNSAID Gel | Pain When Going Up Or Down Stairs | None | 4 Participants |
| Vehicle | Pain When Going Up Or Down Stairs | Extreme | 5 Participants |
| Vehicle | Pain When Going Up Or Down Stairs | None | 4 Participants |
| Vehicle | Pain When Going Up Or Down Stairs | Mild | 32 Participants |
| Vehicle | Pain When Going Up Or Down Stairs | Moderate | 37 Participants |
| Vehicle | Pain When Going Up Or Down Stairs | Severe | 40 Participants |
Primary
Pain When Going Up Or Down Stairs
Participants rate their pain intensity when going up or down stairs as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.
Time frame: at Baseline
Population: mITT population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PENNSAID Gel | Pain When Going Up Or Down Stairs | Mild | 1 Participants |
| PENNSAID Gel | Pain When Going Up Or Down Stairs | Severe | 80 Participants |
| PENNSAID Gel | Pain When Going Up Or Down Stairs | Moderate | 14 Participants |
| PENNSAID Gel | Pain When Going Up Or Down Stairs | Extreme | 35 Participants |
| PENNSAID Gel | Pain When Going Up Or Down Stairs | None | 0 Participants |
| Vehicle | Pain When Going Up Or Down Stairs | Extreme | 30 Participants |
| Vehicle | Pain When Going Up Or Down Stairs | None | 0 Participants |
| Vehicle | Pain When Going Up Or Down Stairs | Mild | 1 Participants |
| Vehicle | Pain When Going Up Or Down Stairs | Moderate | 14 Participants |
| Vehicle | Pain When Going Up Or Down Stairs | Severe | 84 Participants |
Primary
Pain When Walking On A Flat Surface
Participants rate their pain intensity when walking on a flat surface as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.
Time frame: at Baseline
Population: mITT population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PENNSAID Gel | Pain When Walking On A Flat Surface | Mild | 8 Participants |
| PENNSAID Gel | Pain When Walking On A Flat Surface | Severe | 51 Participants |
| PENNSAID Gel | Pain When Walking On A Flat Surface | Moderate | 62 Participants |
| PENNSAID Gel | Pain When Walking On A Flat Surface | Extreme | 9 Participants |
| PENNSAID Gel | Pain When Walking On A Flat Surface | None | 0 Participants |
| Vehicle | Pain When Walking On A Flat Surface | Extreme | 14 Participants |
| Vehicle | Pain When Walking On A Flat Surface | None | 1 Participants |
| Vehicle | Pain When Walking On A Flat Surface | Mild | 4 Participants |
| Vehicle | Pain When Walking On A Flat Surface | Moderate | 67 Participants |
| Vehicle | Pain When Walking On A Flat Surface | Severe | 43 Participants |
Primary
Pain When Walking On A Flat Surface
Participants rate their pain intensity when walking on a flat surface as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.
Time frame: at Week 4
Population: mITT population with non-missing data at Week 4
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PENNSAID Gel | Pain When Walking On A Flat Surface | Mild | 47 Participants |
| PENNSAID Gel | Pain When Walking On A Flat Surface | Severe | 11 Participants |
| PENNSAID Gel | Pain When Walking On A Flat Surface | Moderate | 45 Participants |
| PENNSAID Gel | Pain When Walking On A Flat Surface | Extreme | 1 Participants |
| PENNSAID Gel | Pain When Walking On A Flat Surface | None | 19 Participants |
| Vehicle | Pain When Walking On A Flat Surface | Extreme | 0 Participants |
| Vehicle | Pain When Walking On A Flat Surface | None | 19 Participants |
| Vehicle | Pain When Walking On A Flat Surface | Mild | 38 Participants |
| Vehicle | Pain When Walking On A Flat Surface | Moderate | 51 Participants |
| Vehicle | Pain When Walking On A Flat Surface | Severe | 10 Participants |
Primary
Pain While Sitting Or Lying Down
Participants rate their pain intensity while sitting or lying down as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.
Time frame: at Baseline
Population: mITT population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PENNSAID Gel | Pain While Sitting Or Lying Down | Mild | 30 Participants |
| PENNSAID Gel | Pain While Sitting Or Lying Down | Severe | 30 Participants |
| PENNSAID Gel | Pain While Sitting Or Lying Down | Moderate | 63 Participants |
| PENNSAID Gel | Pain While Sitting Or Lying Down | Extreme | 6 Participants |
| PENNSAID Gel | Pain While Sitting Or Lying Down | None | 1 Participants |
| Vehicle | Pain While Sitting Or Lying Down | Extreme | 12 Participants |
| Vehicle | Pain While Sitting Or Lying Down | None | 4 Participants |
| Vehicle | Pain While Sitting Or Lying Down | Mild | 22 Participants |
| Vehicle | Pain While Sitting Or Lying Down | Moderate | 63 Participants |
| Vehicle | Pain While Sitting Or Lying Down | Severe | 28 Participants |
Primary
Pain While Sitting Or Lying Down
Participants rate their pain intensity while sitting or lying down as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.
Time frame: at Week 4
Population: mITT population with non-missing data at Week 4
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PENNSAID Gel | Pain While Sitting Or Lying Down | Mild | 46 Participants |
| PENNSAID Gel | Pain While Sitting Or Lying Down | Severe | 5 Participants |
| PENNSAID Gel | Pain While Sitting Or Lying Down | Moderate | 36 Participants |
| PENNSAID Gel | Pain While Sitting Or Lying Down | Extreme | 0 Participants |
| PENNSAID Gel | Pain While Sitting Or Lying Down | None | 36 Participants |
| Vehicle | Pain While Sitting Or Lying Down | Extreme | 0 Participants |
| Vehicle | Pain While Sitting Or Lying Down | None | 25 Participants |
| Vehicle | Pain While Sitting Or Lying Down | Mild | 55 Participants |
| Vehicle | Pain While Sitting Or Lying Down | Moderate | 34 Participants |
| Vehicle | Pain While Sitting Or Lying Down | Severe | 4 Participants |
Primary
Pain While Standing
Participants rate their pain intensity while standing as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.
Time frame: at Baseline
Population: mITT population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PENNSAID Gel | Pain While Standing | Mild | 7 Participants |
| PENNSAID Gel | Pain While Standing | Severe | 53 Participants |
| PENNSAID Gel | Pain While Standing | Moderate | 54 Participants |
| PENNSAID Gel | Pain While Standing | Extreme | 16 Participants |
| PENNSAID Gel | Pain While Standing | None | 0 Participants |
| Vehicle | Pain While Standing | Extreme | 18 Participants |
| Vehicle | Pain While Standing | None | 2 Participants |
| Vehicle | Pain While Standing | Mild | 6 Participants |
| Vehicle | Pain While Standing | Moderate | 52 Participants |
| Vehicle | Pain While Standing | Severe | 51 Participants |
Primary
Pain While Standing
Participants rate their pain intensity while standing as none, mild, moderate, severe or extreme. The number of participants who rate their pain in each category is presented.
Time frame: at Week 4
Population: mITT population with non-missing data at Week 4
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PENNSAID Gel | Pain While Standing | None | 15 Participants |
| PENNSAID Gel | Pain While Standing | Moderate | 49 Participants |
| PENNSAID Gel | Pain While Standing | Extreme | 1 Participants |
| PENNSAID Gel | Pain While Standing | Severe | 11 Participants |
| PENNSAID Gel | Pain While Standing | Mild | 47 Participants |
| Vehicle | Pain While Standing | Extreme | 2 Participants |
| Vehicle | Pain While Standing | None | 13 Participants |
| Vehicle | Pain While Standing | Mild | 42 Participants |
| Vehicle | Pain While Standing | Moderate | 50 Participants |
| Vehicle | Pain While Standing | Severe | 11 Participants |