Osteoarthritis, Knee
Conditions
Keywords
Primary Disease: Knee Primary Osteoarthritis
Brief summary
Matrix metalloproteinases (MMPs) have been implicated in the cartilage degradation. PG-530742 inhibits some MMPs, potentially limiting cartilage degradation and disease progression. This study will test the efficacy and safety of PG-530742 in the treatment of mild to moderate knee osteoarthritis.
Detailed description
Matrix metalloproteinases have been implicated in the cartilage degradation that occurs in osteoarthritis. PG-530742 inhibits some of these matrix metalloproteinases, thus potentially limiting cartilage degradation and disease progression. This study will test the efficacy and safety of PG-530742 in the treatment of mild to moderate knee osteoarthritis.
Interventions
DRUG200 mg PG-530742
200 mg PG-530742 tablet, twice a day for one year
DRUG50 mg PG-530742
One 50 mg PG-530742 tablet, twice daily for for one year
DRUG100 mg PG-530742
100 mg PG-530742 tablet, twice a day for one year
DRUGPG-530742
One 25 mg PG-530742 tablet, twice daily for for one year
DRUGPlacebo
One placebo tablet, twice daily for for one year
Sponsors
Procter and Gamble
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* mild to moderate knee osteoarthritis confirmed by a radiographic technique.
Exclusion criteria
* secondary knee osteoarthritis; * diseases other than osteoarthritis that could cause knee pain; * any disease or intervention (surgery, intra-articular injection) that would have an impact on knee pain or mobility; * drugs that act potentially on the bone or cartilage component of the knee joint.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Minimum Joint Space Width in the Medial Compartment of the Tibiofemoral Joint of the Signal Knee After 1 Year of Treatment | baseline and 12 months | The structural primary efficacy endpoint is the 1-year change from baseline in minimum joint space width (JSW) in the medial compartment of the tibiofemoral joint of the signal knee, as measured by microfocal knee radiographs obtained in the semi-flexed position. |
| Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score at 1 Year | baseline and 12 months | The symptomatic primary efficacy endpoint is the change in total WOMAC scores after 1 year of treatment. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items), Stiffness (2 items), Physical Function (17 items). The WOMAC uses descriptors for all items: none, mild moderate, severe, and extreme (corresponding to an ordinal scale of 0-4.) Scores are summed for items in each subscale, with possible ranges as follows: pain=0-20, stiffness=0-8, physical function=0-68. The total WOMAC score is created by summing the items for all three subscales (min=0, max=96) |
Countries
Hungary, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Tablet Placebo tablet dosed BID | 77 |
| 25 mg PG-530742 25 mg PG-530742 dosed BID | 80 |
| 50 mg PG-530742 50 mg PG-530742 dosed BID | 79 |
| 100 mg PG-530742 100 mg PG-530742 dosed BID | 80 |
| 200 mg PG-530742 200 mg PG-530742 dosed BID | 79 |
| Total | 395 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 10 | 6 | 11 | 34 |
| Overall Study | Data Monitoring Committee Recommendation | 0 | 0 | 0 | 0 | 21 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 2 | 2 | 1 |
| Overall Study | Unable to meet protocol criteria | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 4 | 2 | 3 |
Baseline characteristics
| Characteristic | Placebo Tablet | 25 mg PG-530742 | 50 mg PG-530742 | 100 mg PG-530742 | 200 mg PG-530742 | Total |
|---|---|---|---|---|---|---|
| Age Continuous | 62.0 years STANDARD_DEVIATION 0.92 | 62.4 years STANDARD_DEVIATION 0.86 | 62.6 years STANDARD_DEVIATION 0.92 | 62.9 years STANDARD_DEVIATION 0.95 | 63.1 years STANDARD_DEVIATION 0.8 | 62.6 years STANDARD_DEVIATION 0.4 |
| Race/Ethnicity, Customized American Indian | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian Indian | 0 participants | 0 participants | 1 participants | 4 participants | 3 participants | 8 participants |
| Race/Ethnicity, Customized Asian Oriental | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black | 0 participants | 1 participants | 1 participants | 1 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized Caucasian | 77 participants | 79 participants | 77 participants | 75 participants | 76 participants | 384 participants |
| Race/Ethnicity, Customized Hispanic | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Multi-Racial | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 54 Participants | 60 Participants | 61 Participants | 57 Participants | 49 Participants | 281 Participants |
| Sex: Female, Male Male | 23 Participants | 20 Participants | 18 Participants | 23 Participants | 30 Participants | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 77 | 41 / 80 | 34 / 79 | 43 / 80 | 44 / 79 |
| serious Total, serious adverse events | 8 / 77 | 7 / 80 | 12 / 79 | 10 / 80 | 17 / 79 |
Outcome results
Primary
Change in Minimum Joint Space Width in the Medial Compartment of the Tibiofemoral Joint of the Signal Knee After 1 Year of Treatment
The structural primary efficacy endpoint is the 1-year change from baseline in minimum joint space width (JSW) in the medial compartment of the tibiofemoral joint of the signal knee, as measured by microfocal knee radiographs obtained in the semi-flexed position.
Time frame: baseline and 12 months
Population: An intent-to-treat (ITT) analysis was conducted on all patients who were randomized and took at least one dose of study drug. Any missing data for these patients was not imputed in the primary analysis.~analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Tablet | Change in Minimum Joint Space Width in the Medial Compartment of the Tibiofemoral Joint of the Signal Knee After 1 Year of Treatment | -0.1361 mm | Standard Error 0.0627 |
| 25 mg PG-530742 | Change in Minimum Joint Space Width in the Medial Compartment of the Tibiofemoral Joint of the Signal Knee After 1 Year of Treatment | -0.0442 mm | Standard Error 0.0624 |
| 50 mg PG-530742 | Change in Minimum Joint Space Width in the Medial Compartment of the Tibiofemoral Joint of the Signal Knee After 1 Year of Treatment | -0.2261 mm | Standard Error 0.065 |
| 100 mg PG-530742 | Change in Minimum Joint Space Width in the Medial Compartment of the Tibiofemoral Joint of the Signal Knee After 1 Year of Treatment | -0.2000 mm | Standard Error 0.065 |
| 200 mg PG-530742 | Change in Minimum Joint Space Width in the Medial Compartment of the Tibiofemoral Joint of the Signal Knee After 1 Year of Treatment | -0.1916 mm | Standard Error 0.0723 |
Primary
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score at 1 Year
The symptomatic primary efficacy endpoint is the change in total WOMAC scores after 1 year of treatment. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items), Stiffness (2 items), Physical Function (17 items). The WOMAC uses descriptors for all items: none, mild moderate, severe, and extreme (corresponding to an ordinal scale of 0-4.) Scores are summed for items in each subscale, with possible ranges as follows: pain=0-20, stiffness=0-8, physical function=0-68. The total WOMAC score is created by summing the items for all three subscales (min=0, max=96)
Time frame: baseline and 12 months
Population: An intent-to-treat (ITT) analysis was conducted on all patients who were randomized and took at least one dose of study drug. Any missing data for these patients was not imputed in the primary analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Tablet | Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score at 1 Year | -9.1 Scores on a scale | Standard Error 2.81 |
| 25 mg PG-530742 | Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score at 1 Year | -6.7 Scores on a scale | Standard Error 2.78 |
| 50 mg PG-530742 | Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score at 1 Year | -10.0 Scores on a scale | Standard Error 2.88 |
| 100 mg PG-530742 | Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score at 1 Year | -5.8 Scores on a scale | Standard Error 2.92 |
| 200 mg PG-530742 | Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score at 1 Year | -9.3 Scores on a scale | Standard Error 3.96 |