Osteoarthritis
Conditions
Brief summary
The purpose of this study is to determine whether Diclofenac \[Test\] Capsules are safe and effective for the treatment of osteoarthritis pain of the hip or knee.
Interventions
DRUGDiclofenac
35 mg bid Capsules
DRUGPlacebo
Capsules
Sponsors
Iroko Pharmaceuticals, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Primary diagnosis of Functional Class I-III OA of the hip or knee with documented osteoarthritis flare at baseline * Chronic user of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or acetaminophen for OA pain * Discontinued all analgesic therapy at Screening * For women of child-bearing potential: a woman who is not pregnant and not nursing, and who is practicing an acceptable method of birth control
Exclusion criteria
* History of allergic reaction or clinically significant intolerance to acetaminophen, aspirin, or any NSAIDS, including diclofenac * Requires continuous use of opioid or opioid combination products to control OA pain of the knee or hip * Clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, or renal disease * Significant difficulties swallowing capsules or unable to tolerate oral medication * Previous participation in another clinical study of Diclofenac Capsules or received any investigational drug or device or investigational therapy within 30 days before Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | Baseline to Week 12/Early Termination | The pain in subjects with osteoarthritis was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score. The WOMAC pain subscale score is calculated as the average of the visual analogue scale (VAS) scores from 5 pain subscale questions. Subjects mark the VAS, which is a horizontal line 100 mm in length, with a single vertical line to indicate their pain level over the last 24 hours, with 0 mm representing No Pain and 100 mm representing Extreme Pain. The WOMAC pain subscale score difference is calculated as the WOMAC pain subscale score assessed at Week 12 minus the WOMAC pain subscale score assessed at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 2 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | Baseline to Week 2 | The pain in subjects with osteoarthritis was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score. The WOMAC pain subscale score is calculated as the average of the visual analogue scale (VAS) scores from 5 pain subscale questions. Subjects mark the VAS, which is a horizontal line 100 mm in length, with a single vertical line to indicate their pain level over the last 24 hours, with 0 mm representing No Pain and 100 mm representing Extreme Pain. The WOMAC pain subscale score difference was calculated as the WOMAC pain subscale score assessed at Week 2 minus the WOMAC pain subscale score assessed at baseline. |
| Change From Baseline to Week 6 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | Baseline to Week 6 | The pain in subjects with osteoarthritis was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score. The WOMAC pain subscale score is calculated as the average of the visual analogue scale (VAS) scores from 5 pain subscale questions. Subjects mark the VAS, which is a horizontal line 100 mm in length, with a single vertical line to indicate their pain level over the last 24 hours, with 0 mm representing No Pain and 100 mm representing Extreme Pain. The WOMAC pain subscale score difference was calculated as the WOMAC pain subscale score assessed at Week 6 minus the WOMAC pain subscale score assessed at baseline. |
| Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | Baseline to Week 12/Early Termination | The pain in subjects with osteoarthritis was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score. The WOMAC pain subscale score is calculated as the average of the visual analogue scale (VAS) scores from 5 pain subscale questions. Subjects mark the VAS, which is a horizontal line 100 mm in length, with a single vertical line to indicate their pain level over the last 24 hours, with 0 mm representing No Pain and 100 mm representing Extreme Pain. The WOMAC pain subscale score difference was calculated as the WOMAC pain subscale score assessed at Weeks 2, 6, and 12 minus the average of the WOMAC pain subscale score assessed at baseline. |
| Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Osteoarthritis Pain, Stiffness, and Function Measured Using the Total (Composite) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score. | Baseline to Week 12/Early Termination | Pain, stiffness, and function in subjects with osteoarthritis were measured using the Western Ontario and McMaster Universities (WOMAC) Index, which is a 24-item questionnaire. The total (composite) WOMAC score is calculated as the average of the mean visual analogue scale (VAS) scores from the questions in the pain, stiffness, and function subscales. Subjects mark the VAS, which is a horizontal line 100 mm in length, with a single vertical line to indicate their response to each of the questions, with 0 mm representing No Pain, Stiffness, or Difficulty and 100 mm representing Extreme Pain, Stiffness, and Difficulty. The total (composite) WOMAC score difference was calculated as the total (composite) WOMAC score assessed at Weeks 2, 6, and 12 minus the total (composite) WOMAC score assessed at baseline. |
| Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale. | Baseline to Week 12/Early Termination | The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Pain Imaginable. The VAS pain intensity difference is calculated as the average of the VAS pain intensity scores at Weeks 2, 6, and 12 minus the VAS pain intensity at baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diclofenac 35 mg Two Times Daily Diclofenac (two times daily): Capsules | 104 |
| Diclofenac 35 mg Three Times Daily Diclofenac (three times daily): Capsules | 98 |
| Placebo Placebo: Capsule | 103 |
| Total | 305 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 12 | 4 |
| Overall Study | Lack of Efficacy | 2 | 0 | 6 |
| Overall Study | Lost to Follow-up | 0 | 0 | 3 |
| Overall Study | Protocol Violation | 1 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 3 | 2 |
Baseline characteristics
| Characteristic | Diclofenac 35 mg Three Times Daily | Placebo | Diclofenac 35 mg Two Times Daily | Total |
|---|---|---|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 9.9 | 61.8 years STANDARD_DEVIATION 8.42 | 61.4 years STANDARD_DEVIATION 8.33 | 61.6 years STANDARD_DEVIATION 8.87 |
| Baseline Pain Intensity Visual Analogue Scale Score | 71.8 mm STANDARD_DEVIATION 19.33 | 71.5 mm STANDARD_DEVIATION 18.82 | 69.6 mm STANDARD_DEVIATION 19.99 | 71.0 mm STANDARD_DEVIATION 19.35 |
| Baseline Total (Composite) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Sc | 72.83 mm STANDARD_DEVIATION 15.87 | 71.60 mm STANDARD_DEVIATION 17.24 | 70.26 mm STANDARD_DEVIATION 15.69 | 71.54 mm STANDARD_DEVIATION 16.27 |
| Baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score | 76.18 mm STANDARD_DEVIATION 14.15 | 75.27 mm STANDARD_DEVIATION 17.27 | 73.42 mm STANDARD_DEVIATION 15.22 | 74.93 mm STANDARD_DEVIATION 15.61 |
| Body Mass Index | 31.8 kg/m^2 STANDARD_DEVIATION 5.09 | 31.3 kg/m^2 STANDARD_DEVIATION 5.18 | 30.6 kg/m^2 STANDARD_DEVIATION 5.18 | 31.2 kg/m^2 STANDARD_DEVIATION 5.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 8 Participants | 7 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants | 95 Participants | 97 Participants | 288 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 167.60 cm STANDARD_DEVIATION 9.794 | 168.70 cm STANDARD_DEVIATION 9.245 | 169.91 cm STANDARD_DEVIATION 10.561 | 168.76 cm STANDARD_DEVIATION 9.898 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 14 participants | 20 participants | 23 participants | 57 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized White or Caucasian | 83 participants | 82 participants | 80 participants | 245 participants |
| Sex: Female, Male Female | 68 Participants | 71 Participants | 64 Participants | 203 Participants |
| Sex: Female, Male Male | 30 Participants | 32 Participants | 40 Participants | 102 Participants |
| Weight | 89.35 kg STANDARD_DEVIATION 16.552 | 89.44 kg STANDARD_DEVIATION 17.991 | 88.16 kg STANDARD_DEVIATION 17.037 | 88.97 kg STANDARD_DEVIATION 17.167 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 104 | 21 / 98 | 13 / 103 |
| serious Total, serious adverse events | 3 / 104 | 4 / 98 | 2 / 103 |
Outcome results
Primary
Change From Baseline to Week 12 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score.
The pain in subjects with osteoarthritis was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score. The WOMAC pain subscale score is calculated as the average of the visual analogue scale (VAS) scores from 5 pain subscale questions. Subjects mark the VAS, which is a horizontal line 100 mm in length, with a single vertical line to indicate their pain level over the last 24 hours, with 0 mm representing No Pain and 100 mm representing Extreme Pain. The WOMAC pain subscale score difference is calculated as the WOMAC pain subscale score assessed at Week 12 minus the WOMAC pain subscale score assessed at baseline.
Time frame: Baseline to Week 12/Early Termination
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug and had available measurements at the time specified.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac 35 mg Two Times Daily | Change From Baseline to Week 12 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -39.04 mm | Standard Error 2.905 |
| Diclofenac 35 mg Three Times Daily | Change From Baseline to Week 12 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -44.14 mm | Standard Error 3.07 |
| Placebo | Change From Baseline to Week 12 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -32.46 mm | Standard Error 2.937 |
p-value: 0.002495% CI: [-19.17, -4.19]Mixed Models Analysis
p-value: 0.079595% CI: [-13.94, 0.78]Mixed Models Analysis
Secondary
Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score.
The pain in subjects with osteoarthritis was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score. The WOMAC pain subscale score is calculated as the average of the visual analogue scale (VAS) scores from 5 pain subscale questions. Subjects mark the VAS, which is a horizontal line 100 mm in length, with a single vertical line to indicate their pain level over the last 24 hours, with 0 mm representing No Pain and 100 mm representing Extreme Pain. The WOMAC pain subscale score difference was calculated as the WOMAC pain subscale score assessed at Weeks 2, 6, and 12 minus the average of the WOMAC pain subscale score assessed at baseline.
Time frame: Baseline to Week 12/Early Termination
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug and had available measurements at the time specified.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac 35 mg Two Times Daily | Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -35.62 mm | Standard Error 2.633 |
| Diclofenac 35 mg Three Times Daily | Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -41.38 mm | Standard Error 2.796 |
| Placebo | Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -28.14 mm | Standard Error 2.647 |
p-value: 0.024895% CI: [-14, -0.96]ANCOVA
p-value: 0.000195% CI: [-19.89, -6.59]ANCOVA
Secondary
Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Osteoarthritis Pain, Stiffness, and Function Measured Using the Total (Composite) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score.
Pain, stiffness, and function in subjects with osteoarthritis were measured using the Western Ontario and McMaster Universities (WOMAC) Index, which is a 24-item questionnaire. The total (composite) WOMAC score is calculated as the average of the mean visual analogue scale (VAS) scores from the questions in the pain, stiffness, and function subscales. Subjects mark the VAS, which is a horizontal line 100 mm in length, with a single vertical line to indicate their response to each of the questions, with 0 mm representing No Pain, Stiffness, or Difficulty and 100 mm representing Extreme Pain, Stiffness, and Difficulty. The total (composite) WOMAC score difference was calculated as the total (composite) WOMAC score assessed at Weeks 2, 6, and 12 minus the total (composite) WOMAC score assessed at baseline.
Time frame: Baseline to Week 12/Early Termination
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug and had available measurements at the times specified.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac 35 mg Two Times Daily | Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Osteoarthritis Pain, Stiffness, and Function Measured Using the Total (Composite) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score. | -30.25 mm | Standard Error 2.632 |
| Diclofenac 35 mg Three Times Daily | Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Osteoarthritis Pain, Stiffness, and Function Measured Using the Total (Composite) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score. | -35.86 mm | Standard Error 2.798 |
| Placebo | Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Osteoarthritis Pain, Stiffness, and Function Measured Using the Total (Composite) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score. | -23.22 mm | Standard Error 2.656 |
p-value: 0.000295% CI: [-19.32, -5.94]ANCOVA
p-value: 0.036395% CI: [-13.6, -0.45]ANCOVA
Secondary
Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale.
The pain intensity is assessed using a visual analogue scale (VAS), which is a horizontal line 100 mm in length. Subjects mark the VAS with a single vertical line to indicate their current pain level, with 0 mm representing No Pain and 100 mm representing Worst Pain Imaginable. The VAS pain intensity difference is calculated as the average of the VAS pain intensity scores at Weeks 2, 6, and 12 minus the VAS pain intensity at baseline.
Time frame: Baseline to Week 12/Early Termination
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug and had available measurements at the times specified.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac 35 mg Two Times Daily | Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale. | -36.41 mm | Standard Error 2.67 |
| Diclofenac 35 mg Three Times Daily | Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale. | -41.33 mm | Standard Error 2.83 |
| Placebo | Change From Baseline to the Average of Weeks 2, 6, and 12 After Trial Entry in Pain Intensity Difference Measured Using the 100-mm Visual Analogue Scale. | -30.95 mm | Standard Error 2.69 |
p-value: 0.002895% CI: [-17.16, -3.6]ANCOVA
p-value: 0.108195% CI: [-12.13, 1.21]ANCOVA
Secondary
Change From Baseline to Week 2 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score.
The pain in subjects with osteoarthritis was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score. The WOMAC pain subscale score is calculated as the average of the visual analogue scale (VAS) scores from 5 pain subscale questions. Subjects mark the VAS, which is a horizontal line 100 mm in length, with a single vertical line to indicate their pain level over the last 24 hours, with 0 mm representing No Pain and 100 mm representing Extreme Pain. The WOMAC pain subscale score difference was calculated as the WOMAC pain subscale score assessed at Week 2 minus the WOMAC pain subscale score assessed at baseline.
Time frame: Baseline to Week 2
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug and had available measurements at the time specified.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac 35 mg Two Times Daily | Change From Baseline to Week 2 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -31.40 mm | Standard Error 2.742 |
| Diclofenac 35 mg Three Times Daily | Change From Baseline to Week 2 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -37.42 mm | Standard Error 2.907 |
| Placebo | Change From Baseline to Week 2 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -21.60 mm | Standard Error 2.787 |
p-value: <0.000195% CI: [-22.82, -8.83]Mixed Models Analysis
p-value: 0.005295% CI: [-16.66, -2.95]Mixed Models Analysis
Secondary
Change From Baseline to Week 6 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score.
The pain in subjects with osteoarthritis was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score. The WOMAC pain subscale score is calculated as the average of the visual analogue scale (VAS) scores from 5 pain subscale questions. Subjects mark the VAS, which is a horizontal line 100 mm in length, with a single vertical line to indicate their pain level over the last 24 hours, with 0 mm representing No Pain and 100 mm representing Extreme Pain. The WOMAC pain subscale score difference was calculated as the WOMAC pain subscale score assessed at Week 6 minus the WOMAC pain subscale score assessed at baseline.
Time frame: Baseline to Week 6
Population: Intent-to-Treat Population. All subjects who received at least 1 dose of trial drug and had available measurements at the time specified.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Diclofenac 35 mg Two Times Daily | Change From Baseline to Week 6 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -36.64 mm | Standard Error 2.889 |
| Diclofenac 35 mg Three Times Daily | Change From Baseline to Week 6 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -43.51 mm | Standard Error 3.051 |
| Placebo | Change From Baseline to Week 6 After Trial Entry in Osteoarthritis Pain Measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. | -31.08 mm | Standard Error 2.922 |
p-value: 0.134995% CI: [-12.86, 1.74]Mixed Models Analysis
p-value: 0.001195% CI: [-19.87, -4.99]Mixed Models Analysis