Ankle Sprain
Conditions
Keywords
Pain due to ankle sprain
Brief summary
To demonstrate the therapeutic efficacy of a generic diclofenac epolamine patch against Flector patch in the treatment of pain in subjects with minor ankle sprain
Detailed description
To evaluate the therapeutic equivalence and safety of generic diclofenac epolamine 1.3% patch (Watson Laboratories, Inc.) and Flector® (diclofenac epolamine 1.3% patch) (Pfizer) in the treatment of acute pain due to minor ankle sprain. To demonstrate the superiority of the efficacy of the test and reference products over that of the vehicle control in the treatment of acute pain due to minor ankle sprain. To access application site reactions and patch adhesion between treatment groups.
Interventions
DRUGDiclofenac epolamine
Diclofenac epolamine in a topical patch formulation; applied to the area of sprained ankle; to treat pain associated with a mild ankle sprain
OTHERPlacebo
Topical patch not containing diclofenac epolamine applied to the area of sprained ankle; to treat pain associated with a mild ankle sprain
Sponsors
Actavis Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or Non pregnant females, 18-65 years of age 2. Signed informed consent obtained that meets all criteria of current FDA and Health Insurance Portability and Accountability Act regulations 3. Subject has a diagnosis of uncomplicated acute minor ankle sprain: Grade I and II (as defined by the America Academy of Orthopedic Surgeons AAOS) 4. Ankle sprain must have occurred \< 48 hours before study entry with baseline pain score of \> 50 mm on a 100 mm Visual Analog Scale (VAS) upon active mobilization 5. Female subjects of childbearing potential (excluding women who are surgically sterilized or postmenopausal for at least 1 year), in addition to having a negative urine pregnancy test, must be willing to use an acceptable form of birth control during the study from the day of the first dose administration to 30 days after the last administration of study drug. For the purpose of this study the following are considered acceptable methods of birth control: oral or injectable contraceptives, contraceptive patches, Depo-Provera® (on stable treatment for at least 3 months) NuvaRing® (vaginal contraceptive); Implanon™ (contraceptive implant) double barrier methods (e.g. condom and spermicide), intrauterine device, or abstinence with a 2nd acceptable method of birth control, should the patient become sexually active. A sterile sexual partner is NOT considered an adequate form of birth control. 6. All male subjects must agree to use accepted methods of birth control with their partners, from the day of the first dose administration to 30 days after the last administration of study drug. Abstinence is an acceptable method of birth control. Female partners should use an acceptable method of birth control as described in Item Number 5. 7. Subject is free from any systemic or dermatologic disorder that, in the opinion of the investigator, will interfere with the study results or increase the risk of adverse events. 8. Subject shows willingness and capability to cooperate to the extent and degree required by the protocol. 9. Subject is willing to refrain from using any other pain medication during their participation.
Exclusion criteria
1. Pregnant or breastfeeding female. 2. Sprain occurred \> 48 hours prior to study enrollment. 3. Ankle sprain requires an orthopedic or surgical treatment. 4. Ankle sprain treated prior to study entry by topical, oral, or parenteral nonsteroidal antiinflammatory drug (NSAID), physiotherapy, ultrasound, physical therapy or acupuncture. 5. Baseline self-evaluation of pain on active mobilization by the VAS \< 50 mm. 6. Non-intact or damaged skin within the area to be treated, e.g., eczema, psoriasis, exudative, dermatitis, infected lesion, burn or wound. 7. Medical history of asthma, urticaria, angioedema, bronchospasm, ulcer disease, gastrointestinal bleeding, hypertension, edema, heart failure or cardiovascular disease. 8. Medical history of any chronic pain disorder. 9. Coagulation defects. 10. Severe cardiac, renal or hepatic impairment. 11. Severe systemic disease (e.g., cancer, severe acute infection). 12. Use within one month prior to randomization of 1.) immunomodulators or immunosuppressive therapies, 2.) interferon, 3.) oral or parenteral corticosteroids or 4.) cytotoxic drugs. 13. Use within 7 days prior to randomization of any topical agents on the affected ankle. 14. Use within 7 days prior to randomization of topical, oral or parenteral treatment with NSAIDs or aspirin. 15. Use within 12 hours prior to randomization of an analgesic. Eg. Acetaminophen (Tylenol®). 16. Known allergy or hypersensitivity to diclofenac, aspirin or other NSAIDs, or any excipient in the test product or brand product (Flector). 17. History of uncontrolled chronic or acute concomitant disease which, in the Investigator's opinion, would contraindicate study participation or confound interpretation of the results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Baseline, 3 days | To evaluate the therapeutic equivalence (90% CI) of generic diclofenac epolamine 1.3% patch (Watson Laboratories, Inc.) and Flector® (diclofenac epolamine 1.3% patch) (Pfizer) using a 100mm VAS scoring in the treatment of acute pain due to minor ankle sprain (in the per protocol population); changes from baseline. The Visual Analogue Scale (VAS) consists of a straight line with the endpoints defining extreme limits such as lower values of 'no pain at all' and higher values relating to 'pain as bad as it could be' . Percent improvement in VAS score is the percentage part of - change from baseline in VAS / Baseline VAS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Baseline, 3 days | To demonstrate the superiority (P\<0.05) of the efficacy of the test and reference products over that of the vehicle control in the treatment of acute pain utilizing a 100 mm VAS (in the mITT population) - changes from baseline. The Visual Analogue Scale (VAS) consists of a straight line with the endpoints defining extreme limits such as lower values of 'no pain at all' and higher values relating to 'pain as bad as it could be' . |
Countries
United States
Participant flow
Pre-assignment details
The populations for this study included the Safety Population, the Per-Protocol Population (PP) and the modified Intent-to-treat (mITT) population.
Participants by arm
| Arm | Count |
|---|---|
| Diclofenac Epolamine Patch (Test Product) Generic Diclofenac Epolamine Topical Patch 1.3% (Watson Laboratories, Inc.)
Diclofenac epolamine: Diclofenac epolamine in a topical patch formulation; applied to the area of sprained ankle; to treat pain associated with a mild ankle sprain | 214 |
| Flector (Reference Product) Flector® (Diclofenac Epolamine Topical Patch 1.3%) (Pfizer)
Diclofenac epolamine: Diclofenac epolamine in a topical patch formulation; applied to the area of sprained ankle; to treat pain associated with a mild ankle sprain | 216 |
| Placebo Placebo patch of the test product (Watson Laboratories, Inc.); Identical in appearance and formulated as the test product, omitting the active ingredient, diclofenac epolamine
Placebo: Topical patch not containing diclofenac epolamine applied to the area of sprained ankle; to treat pain associated with a mild ankle sprain | 217 |
| Total | 647 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 3 | 4 |
| Overall Study | Non Compliance with Study Drug | 1 | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Diclofenac Epolamine Patch (Test Product) | Total | Placebo | Flector (Reference Product) |
|---|---|---|---|---|
| Age, Continuous | 34.7 years STANDARD_DEVIATION 12.1 | 35.0 years STANDARD_DEVIATION 12.6 | 35.5 years STANDARD_DEVIATION 13.3 | 34.9 years STANDARD_DEVIATION 12.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 86 Participants | 247 Participants | 83 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 128 Participants | 400 Participants | 134 Participants | 138 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height (cm) | 171.44 cm STANDARD_DEVIATION 10.74 | 172.30 cm STANDARD_DEVIATION 10.44 | 172.17 cm STANDARD_DEVIATION 9.72 | 173.28 cm STANDARD_DEVIATION 10.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 11 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 60 Participants | 190 Participants | 71 Participants | 59 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 147 Participants | 436 Participants | 140 Participants | 149 Participants |
| Region of Enrollment United States | 214 participants | 647 participants | 217 participants | 216 participants |
| Sex: Female, Male Female | 85 Participants | 246 Participants | 82 Participants | 79 Participants |
| Sex: Female, Male Male | 129 Participants | 401 Participants | 135 Participants | 137 Participants |
| Weight (kg) | 81.73 Kg STANDARD_DEVIATION 19.86 | 83.02 Kg STANDARD_DEVIATION 19.07 | 83.97 Kg STANDARD_DEVIATION 20.1 | 83.34 Kg STANDARD_DEVIATION 17.11 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 214 | 0 / 216 | 0 / 217 |
| other Total, other adverse events | 17 / 214 | 20 / 216 | 22 / 217 |
| serious Total, serious adverse events | 0 / 214 | 0 / 216 | 0 / 217 |
Outcome results
Primary
Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment
To evaluate the therapeutic equivalence (90% CI) of generic diclofenac epolamine 1.3% patch (Watson Laboratories, Inc.) and Flector® (diclofenac epolamine 1.3% patch) (Pfizer) using a 100mm VAS scoring in the treatment of acute pain due to minor ankle sprain (in the per protocol population); changes from baseline. The Visual Analogue Scale (VAS) consists of a straight line with the endpoints defining extreme limits such as lower values of 'no pain at all' and higher values relating to 'pain as bad as it could be' . Percent improvement in VAS score is the percentage part of - change from baseline in VAS / Baseline VAS.
Time frame: Baseline, 3 days
Population: Per Protocol Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diclofenac Epolamine Patch (Test Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Baseline | 68.56 score on a scale | Standard Deviation 11.03 |
| Diclofenac Epolamine Patch (Test Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | 72 Hours after Initial treatment | 25.34 score on a scale | Standard Deviation 17.35 |
| Diclofenac Epolamine Patch (Test Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Change from Baseline | -43.22 score on a scale | Standard Deviation 18.94 |
| Flector (Reference Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Baseline | 69.03 score on a scale | Standard Deviation 10.9 |
| Flector (Reference Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | 72 Hours after Initial treatment | 25.78 score on a scale | Standard Deviation 18.5 |
| Flector (Reference Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Change from Baseline | -43.25 score on a scale | Standard Deviation 20.71 |
90% CI: [0.94, 1.08]
Secondary
Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment
To demonstrate the superiority (P\<0.05) of the efficacy of the test and reference products over that of the vehicle control in the treatment of acute pain utilizing a 100 mm VAS (in the mITT population) - changes from baseline. The Visual Analogue Scale (VAS) consists of a straight line with the endpoints defining extreme limits such as lower values of 'no pain at all' and higher values relating to 'pain as bad as it could be' .
Time frame: Baseline, 3 days
Population: Modified Intent-to-Treat Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diclofenac Epolamine Patch (Test Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | 72 hours after Initial treatment | 25.83 score on a scale | Standard Deviation 18.19 |
| Diclofenac Epolamine Patch (Test Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Baseline | 68.75 score on a scale | Standard Deviation 11.27 |
| Diclofenac Epolamine Patch (Test Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Change from baseline | -42.91 score on a scale | Standard Deviation 19.04 |
| Flector (Reference Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | 72 hours after Initial treatment | 26.16 score on a scale | Standard Deviation 18.47 |
| Flector (Reference Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Baseline | 68.93 score on a scale | Standard Deviation 10.94 |
| Flector (Reference Product) | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Change from baseline | -42.80 score on a scale | Standard Deviation 20.73 |
| Placebo | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Baseline | 70.09 score on a scale | Standard Deviation 11.37 |
| Placebo | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | Change from baseline | -42.88 score on a scale | Standard Deviation 21.66 |
| Placebo | Visual Analogue Scale (VAS) Scores at Baseline and Post Treatment | 72 hours after Initial treatment | 27.16 score on a scale | Standard Deviation 18.18 |
p-value: 0.01ANCOVA
p-value: 0.05ANCOVA