Osteoarthritis of the Knee
Conditions
Brief summary
A 4-week, Randomized, Double-blind, Multicenter, Placebo-controlled Phase 2 Study to Evaluate the Efficacy and Safety of HP-5000 in Subjects with Osteoarthritis (OA) of the Knee
Detailed description
This is a multicenter, randomized, double-blind, and placebo-controlled phase 2 study evaluating 2 formulations of HP-5000 in subjects with OA of the knee. The study will consist of up to 28-day Screening Phase that will include a Washout Period of current prescription and over the counter (OTC) analgesics, a 4-week double-blind Treatment Phase, and a 1-week safety Follow-up Period.
Interventions
DRUGDiclofenac Sodium Active Topical Patch 1
HP-5000 Active Topical Patch 1 were applied on subjects with Osteoarthritis of the knee(s)
DRUGDiclofenac Sodium Active Topical Patch 2
HP-5000 Active Topical Patch 2 were applied on subjects with Osteoarthritis of the knee(s)
DRUGPlacebo patch
Topical placebo patches were applied on subjects with Osteoarthritis of the knee(s)
Sponsors
Noven Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Male or female aged 40 to 85 years with a clinical diagnosis of OA of the target knee according to the American College of Rheumatology (ACR) criteria, including: * Symptoms for at least 6 months prior to screening, AND * Knee pain in the target knee for 30 days of the preceding month (periarticular knee pain due to OA and not due to other conditions such as bursitis, tendonitis, etc.) AND * The pain in the target knee required the use of nonsteroidal anti-inflammatory drugs (NSAIDs) either over the counter (OTC) per recommendation of a physician or prescribed.
Exclusion criteria
* Body mass index (BMI) \> 40 * Any subject who disobeyed the restriction of prohibited therapies (i.e., use rescue medication) during Screening Washout Period. * Secondary OA of the knee (rheumatoid arthritis, gout, psoriasis, syphilitic neuropathy, ochronosis, metabolic or other primary bone disease or acute trauma).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Efficacy & Safety of HP-5000 Topical Patches in Subjects With Osteoarthritis of the Knee: Change in Osteoarthritis Pain Score | Baseline and 4 weeks | To evaluate efficacy of HP-5000 Active Topical Patch 1 and HP-5000 Active Topical Patch 2 compared with placebo for the treatment of Osteoarthritis of the knee as evaluated by change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 4. WOMAC pain score is a scale that evaluate five items including walking, stair climbing, nocturnal, rest and weight bearing. Each item is rated on a scale of 0 to 4, with 0 being no difficulty and 4 being extremely difficulty. The total score is the sum of five items. The total score range from 0 to 20 with a low score considered a better outcome and a high score considered a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| WOMAC Pain Score Week 2 Change From Baseline | Baseline and 2 weeks | To evaluate efficacy of HP-5000 Active Topical Patch 1 and HP-5000 Active Topical Patch 2 compared with placebo for the treatment of Osteoarthritis of the knee as evaluated by change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 2. WOMAC pain score is a scale that evaluate five items including walking, stair climbing, nocturnal, rest and weight bearing. Each item is rated on a scale of 0 to 4, with 0 being no difficulty and 4 being extremely difficulty. The total score is the sum of five items. The total score range from 0 to 20 with a low score considered a better outcome and a high score considered a worse outcome. The total score range from 0 to 20 with a low score considered a better outcome and a high score considered a worse outcome. |
| WOMAC Stiffness Score Change From Baseline | Baseline and 4 weeks | To evaluate efficacy of HP-5000 Active Topical Patch 1 and HP-5000 Active Topical Patch 2 compared with placebo for the treatment of Osteoarthritis of the knee as evaluated by change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score from baseline to week 4. The WOMAC Stiffness scale assesses 2 items including morning stiffness and stiffness occurring later in the day. Each item is rated on a scale of 0 to 4, with 0 being no difficulty and 4 being extremely difficulty. The total score is the sum of two items range from 0 to 8 with a low score considered as a better outcome. |
| WOMAC Physical Function Score | Baseline and 4 weeks | To evaluate efficacy of HP-5000 Active Topical Patch 1 and HP-5000 Active Topical Patch 2 compared with placebo for the treatment of Osteoarthritis of the knee as evaluated by change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function score from baseline to week 4. The WOMAC Physical Function assesses the following 17 items using the 0 to 4 scale. These 17 items include: 1. descending stairs; 2. ascending stairs; 3. rising from sitting; 4. standing; 5. bending to floor; 6. walking on a flat surface; 7. getting in/getting out of car; 8. going shopping; 9. putting on socks; 10. lying in bed; 11. taking off socks; 12. rising from bed; 13. getting in/out of bath; 14. sitting; 15. getting on/off toilet; 16. heavy domestic duties; 17. light domestic duties. Each item is rated on a scale of 0 to 4, with 0 being no difficulty and 4 being extremely difficulty. Total score range from 0 to 68 with lower score considered a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HP-5000-75α Patch (5% Diclofenac Sodium) Diclofenac Sodium Active Topical Patch 1 and Diclofenac Sodium Active Topical Patch 2 contain the same amount of diclofenac sodium but in different formulations.
Diclofenac Sodium Active Topical Patch 1 was applied to the target knee on subjects with Osteoarthritis of the knee(s for 4-week treatment. | 69 |
| HP-5000-DRS400 Patch (5% Diclofenac Sodium) Diclofenac Sodium Active Topical Patch 1 and Diclofenac Sodium Active Topical Patch 2 contain the same amount of diclofenac sodium but in different formulations.
Diclofenac Sodium Active Topical Patch 2 was applied to the target knee on subjects with Osteoarthritis of the knee(s) for 4-week treatment. | 71 |
| Placebo Patch Placebo patch was applied to the target knee on subjects with Osteoarthritis of the knee(s) for 4-week treatment. | 143 |
| Total | 283 |
Baseline characteristics
| Characteristic | HP-5000-75α Patch (5% Diclofenac Sodium) | HP-5000-DRS400 Patch (5% Diclofenac Sodium) | Placebo Patch | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 24 Participants | 31 Participants | 65 Participants | 120 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 40 Participants | 78 Participants | 163 Participants |
| Age, Continuous | 56.1 years STANDARD_DEVIATION 8.66 | 57.1 years STANDARD_DEVIATION 8.65 | 59 years STANDARD_DEVIATION 8.46 | 57.8 years STANDARD_DEVIATION 8.62 |
| BMI | 29.51 kg/m^2 STANDARD_DEVIATION 5.103 | 29.83 kg/m^2 STANDARD_DEVIATION 4.898 | 29.89 kg/m^2 STANDARD_DEVIATION 5.257 | 29.78 kg/m^2 STANDARD_DEVIATION 5.116 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 17 Participants | 34 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 54 Participants | 109 Participants | 212 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 69 Participants | 71 Participants | 143 Participants | 283 Participants |
| Sex: Female, Male Female | 17 Participants | 20 Participants | 36 Participants | 73 Participants |
| Sex: Female, Male Male | 52 Participants | 51 Participants | 107 Participants | 210 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 69 | 0 / 71 | 0 / 143 |
| other Total, other adverse events | 9 / 69 | 8 / 71 | 19 / 143 |
| serious Total, serious adverse events | 0 / 69 | 1 / 71 | 1 / 143 |
Outcome results
Primary
Evaluate Efficacy & Safety of HP-5000 Topical Patches in Subjects With Osteoarthritis of the Knee: Change in Osteoarthritis Pain Score
To evaluate efficacy of HP-5000 Active Topical Patch 1 and HP-5000 Active Topical Patch 2 compared with placebo for the treatment of Osteoarthritis of the knee as evaluated by change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 4. WOMAC pain score is a scale that evaluate five items including walking, stair climbing, nocturnal, rest and weight bearing. Each item is rated on a scale of 0 to 4, with 0 being no difficulty and 4 being extremely difficulty. The total score is the sum of five items. The total score range from 0 to 20 with a low score considered a better outcome and a high score considered a worse outcome.
Time frame: Baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac Sodium Active Topical Patch 1 | Evaluate Efficacy & Safety of HP-5000 Topical Patches in Subjects With Osteoarthritis of the Knee: Change in Osteoarthritis Pain Score | -6.3 score on a scale | Standard Deviation 4.47 |
| Diclofenac Sodium Active Topical Patch 2 | Evaluate Efficacy & Safety of HP-5000 Topical Patches in Subjects With Osteoarthritis of the Knee: Change in Osteoarthritis Pain Score | -5.6 score on a scale | Standard Deviation 4.06 |
| Placebo Patch | Evaluate Efficacy & Safety of HP-5000 Topical Patches in Subjects With Osteoarthritis of the Knee: Change in Osteoarthritis Pain Score | -5.2 score on a scale | Standard Deviation 4.16 |
p-value: 0.011Mixed Models Analysis
p-value: 0.2835Mixed Models Analysis
Secondary
WOMAC Pain Score Week 2 Change From Baseline
To evaluate efficacy of HP-5000 Active Topical Patch 1 and HP-5000 Active Topical Patch 2 compared with placebo for the treatment of Osteoarthritis of the knee as evaluated by change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 2. WOMAC pain score is a scale that evaluate five items including walking, stair climbing, nocturnal, rest and weight bearing. Each item is rated on a scale of 0 to 4, with 0 being no difficulty and 4 being extremely difficulty. The total score is the sum of five items. The total score range from 0 to 20 with a low score considered a better outcome and a high score considered a worse outcome. The total score range from 0 to 20 with a low score considered a better outcome and a high score considered a worse outcome.
Time frame: Baseline and 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac Sodium Active Topical Patch 1 | WOMAC Pain Score Week 2 Change From Baseline | -5.8 score on a scale | Standard Deviation 4.29 |
| Diclofenac Sodium Active Topical Patch 2 | WOMAC Pain Score Week 2 Change From Baseline | -5.3 score on a scale | Standard Deviation 3.67 |
| Placebo Patch | WOMAC Pain Score Week 2 Change From Baseline | -5.0 score on a scale | Standard Deviation 4.01 |
Secondary
WOMAC Physical Function Score
To evaluate efficacy of HP-5000 Active Topical Patch 1 and HP-5000 Active Topical Patch 2 compared with placebo for the treatment of Osteoarthritis of the knee as evaluated by change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function score from baseline to week 4. The WOMAC Physical Function assesses the following 17 items using the 0 to 4 scale. These 17 items include: 1. descending stairs; 2. ascending stairs; 3. rising from sitting; 4. standing; 5. bending to floor; 6. walking on a flat surface; 7. getting in/getting out of car; 8. going shopping; 9. putting on socks; 10. lying in bed; 11. taking off socks; 12. rising from bed; 13. getting in/out of bath; 14. sitting; 15. getting on/off toilet; 16. heavy domestic duties; 17. light domestic duties. Each item is rated on a scale of 0 to 4, with 0 being no difficulty and 4 being extremely difficulty. Total score range from 0 to 68 with lower score considered a better outcome.
Time frame: Baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac Sodium Active Topical Patch 1 | WOMAC Physical Function Score | -19.8 score on a scale | Standard Deviation 14.85 |
| Diclofenac Sodium Active Topical Patch 2 | WOMAC Physical Function Score | -19.3 score on a scale | Standard Deviation 13.63 |
| Placebo Patch | WOMAC Physical Function Score | -15.6 score on a scale | Standard Deviation 13.07 |
Secondary
WOMAC Stiffness Score Change From Baseline
To evaluate efficacy of HP-5000 Active Topical Patch 1 and HP-5000 Active Topical Patch 2 compared with placebo for the treatment of Osteoarthritis of the knee as evaluated by change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score from baseline to week 4. The WOMAC Stiffness scale assesses 2 items including morning stiffness and stiffness occurring later in the day. Each item is rated on a scale of 0 to 4, with 0 being no difficulty and 4 being extremely difficulty. The total score is the sum of two items range from 0 to 8 with a low score considered as a better outcome.
Time frame: Baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac Sodium Active Topical Patch 1 | WOMAC Stiffness Score Change From Baseline | -2.4 score on a scale | Standard Deviation 2.06 |
| Diclofenac Sodium Active Topical Patch 2 | WOMAC Stiffness Score Change From Baseline | -2.1 score on a scale | Standard Deviation 1.94 |
| Placebo Patch | WOMAC Stiffness Score Change From Baseline | -1.7 score on a scale | Standard Deviation 1.77 |