Osteoarthritis
Conditions
Keywords
Knee
Brief summary
To establish the therapeutic equivalence and safety of a generic Diclofenac Sodium Topical Gel, 1% with Voltaren® Gel 1% in subjects with osteoarthritis of the knee.
Interventions
DRUGDiclofenac Sodium Topical Gel, 1%
Opaque, white gel
DRUGVoltaren Topical Gel, 1%
Opaque, white gel
DRUGVehicle Diclofenac Sodium Topical Gel
Opaque, white gel
Sponsors
Sristek Clinical Research Solutions Limited
Amneal Pharmaceuticals, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Healthy, ambulatory male or non-pregnant female subjects aged ≥ 35 years with a clinical diagnosis of OA of the knee. * Had an X-ray of the target knee, taken no more than 1 year before baseline, showing evidence of OA with Kellgren-Lawrence grade 1-3 disease. * After discontinuing all pain medications for at least 7 days, has at least moderate pain on movement for target knee * If female and of child-bearing potential, agree to abstain from sexual intercourse or use a reliable method of contraception during the study * Able to tolerate rescue medication with paracetamol/acetaminophen.
Exclusion criteria
* Pregnant or lactating or planning to become pregnant during the study period. * X-ray showing evidence of OA with Kellgren-Lawrence grade 4 disease. * History of OA pain in the contralateral knee requiring medication within 1 year prior to screening. * After discontinuing all pain medications for at least 7 days, has a baseline score of ≥20 mm on a 0-100 mm Visual Analog Scale (VAS) for the contralateral knee immediately prior to randomization. * History of secondary OA, rheumatoid arthritis, chronic inflammatory disease or fibromyalgia. * History of asthma, hypertension, myocardial infarction, thrombotic events, stroke, congestive heart failure, impaired renal function or liver disease. * History of gastrointestinal bleeding or peptic ulcer disease. * Use of warfarin or other anticoagulant therapy within 30 days of study randomization. * Elevated transaminases at screening. * Use of ACE inhibitors, cyclosporine, diuretics, lithium or methotrexate, within 30 days of study randomization. * Concomitant use of corticosteroids or use within 30 days of study randomization. * Concomitant acetylsalicylic acid therapy other than a stable low dose used for cardiac prophylaxis taken for at least 3 months prior to enrollment and maintained throughout the duration of the study. * Known allergy to aspirin or nonsteroidal anti-inflammatory drug * Any other acute or chronic illness that could compromise the integrity of study data or place the subject at risk by participating in the study. * Receipt of any drug as part of a research study within 30 days prior to screening. * Previous participation in this study. * Any use between screening and baseline of a treatment or medication that may potentially confound study assessment that may potentially confound study assessment (e.g. use of topical analgesics or anti-inflammatory drugs). * Recent history of major knee injury or surgery. * Known history of positive HIV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 4 Weeks in WOMAC Pain Score | Baseline and Week 4 | Mean change from baseline to week 4 in the Western Ontario McMaster Osteoarthritis (WOMAC) pain score: 5-point Likert scale: none=o, mild=1, moderate=2, severe=3, extreme=4 |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diclofenac Sodium Topical Gel, 1% Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks
Diclofenac Sodium Topical Gel, 1%: Opaque, white gel | 391 |
| Voltaren Topical Gel, 1% Voltaren Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks
Voltaren Topical Gel, 1%: Opaque, white gel | 393 |
| Vehicle Diclofenac Sodium Topical Gel Vehicle Diclofenac Sodium Topical Gel. 4 gm, 4 times a day for 4 weeks
Vehicle Diclofenac Sodium Topical Gel: Opaque, white gel | 391 |
| Total | 1,175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Concomitant therapy | 0 | 1 | 1 |
| Overall Study | Others | 1 | 0 | 1 |
| Overall Study | Physician Decision | 2 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 2 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 4 |
Baseline characteristics
| Characteristic | Diclofenac Sodium Topical Gel, 1% | Voltaren Topical Gel, 1% | Vehicle Diclofenac Sodium Topical Gel | Total |
|---|---|---|---|---|
| Age, Customized <= 18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=65year | 34 Participants | 42 Participants | 37 Participants | 113 Participants |
| Age, Customized between 18 and 65 years | 357 Participants | 351 Participants | 354 Participants | 1062 Participants |
| Sex: Female, Male Female | 255 Participants | 244 Participants | 254 Participants | 753 Participants |
| Sex: Female, Male Male | 136 Participants | 149 Participants | 137 Participants | 422 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 391 | 0 / 393 | 0 / 391 |
| other Total, other adverse events | 2 / 391 | 2 / 393 | 3 / 391 |
| serious Total, serious adverse events | 0 / 391 | 0 / 393 | 0 / 391 |
Outcome results
Primary
Change From Baseline to 4 Weeks in WOMAC Pain Score
Mean change from baseline to week 4 in the Western Ontario McMaster Osteoarthritis (WOMAC) pain score: 5-point Likert scale: none=o, mild=1, moderate=2, severe=3, extreme=4
Time frame: Baseline and Week 4
Population: Across study groups, the per protocol (PP) population included 1147 subjects (97.53%) and the modified intention-to-treat (mITT) population included 1166 subjects (99.15%).~For various reasons, 10 subjects were excluded from mITT population while 29 subjects were excluded from PP population out of 1176 subjects randomized in the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac Sodium Topical Gel, 1% | Change From Baseline to 4 Weeks in WOMAC Pain Score | 2.2332 score on a scale | Standard Error 0.116 |
| Voltaren Topical Gel, 1% | Change From Baseline to 4 Weeks in WOMAC Pain Score | 2.0287 score on a scale | Standard Error 0.1157 |
| Vehicle Diclofenac Sodium Topical Gel | Change From Baseline to 4 Weeks in WOMAC Pain Score | -0.6387 score on a scale | Standard Error 0.1172 |