Acute Gout Flare
Conditions
Keywords
Metabolism, Inborn Errors, Allopurinol, Metabolic Diseases, Genetic Diseases, Inborn, Musculoskeletal Diseases, Joint Diseases, Arthritis, Rheumatic Diseases, Metabolic disorder, Purine-Pyrimidine Metabolism, Inborn Errors, Gout, Flare
Brief summary
This purpose of this clinical research was to determine the efficacy and safety of an experimental drug called Rilonacept in participants with an acute gout attack. Participants participated in this study for 30 days. Rilonacept alone was being compared with Indomethacin alone and the combination of Rilonacept plus Indomethacin in treating acute gout flares.
Interventions
DRUGRilonacept
Two subcutaneous injections of Rilonacept 160 mg (for a total of 320 mg) on Day 1 (Baseline).
DRUGIndomethacin
Indomethacin orally TID for 12 days (Indomethacin 50 mg for first 3 days and then, Indomethacin 25 mg for next 9 days).
OTHERPlacebo (for Indomethacin)
Placebo (for Indomethacin) orally TID for 12 days.
Two subcutaneous injections of Placebo (for Rilonacept) on Day 1 (Baseline).
Sponsors
Regeneron Pharmaceuticals
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 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female 18 - 70 years of age 2. Previously met the preliminary criteria of ARA for the classification of the acute arthritis of primary gout 3. Presenting with an acute attack (flare) of gout within 48 hours of pain onset and pain of at least moderate severity 4. Must have at least 1 on the 0-3 scale for the swelling and the tenderness assessments of the gouty index joint 5. Current presentation of acute gout flare in 3 joints or less
Exclusion criteria
1. Treatment with any non-steroidal anti-inflammatory drug (NSAIDs) or opiates within 48 hours prior to baseline assessments. Treatment with long-acting NSAIDs within 1 month prior to baseline visit. Treatment with naproxen, meloxicam, nabumetone, celecoxib and indomethacin SR within 5 days prior to baseline visit. 2. Treatment with oral analgesics within 6 hours before baseline assessments. Treatment with topical analgesics within 12 hours before baseline assessments 3. History of NSAID intolerance 4. Participants with history of chronic, gouty arthritis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint to Averaged PAP-LS at 24, 48 and 72 Hours | Pre-dose on Day 1 (Baseline); post-dose at 4, 8, 12, 24, 48, 72 hours and then daily up to Day 13 or until gout flare ends | Participants were asked to complete a daily diary entry and assessed their pain in the past 24 hours using 5-point Likert Scale of 0 (None) to 4 (extreme pain), where; 0= none, 1= mild pain, 2= moderate pain, 3= severe pain, or 4= extreme pain. Change in PAP-LS in the index joint from baseline (Day 1) to the averaged PAP-LS values at 24, 48 and 72 hours was reported in this outcome measure (averaged PAP value= \[PAP at 24 hours + PAP at 48 hours + PAP at 72 hours\]/3). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 72 Hours | Baseline (Day 1) to 72 hours | Participants were asked to complete a daily diary entry and assessed their pain in the past 24 hours using 5-point Likert Scale of 0 (None) to 4 (extreme pain), where; 0= none, 1= mild pain, 2= moderate pain, 3= severe pain, or 4= extreme pain. |
| Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 48 Hours | Baseline (Day 1) to 48 hours | Participants were asked to complete a daily diary entry and assessed their pain in the past 24 hours using 5-point Likert Scale of 0 (None) to 4 (extreme pain), where; 0= none, 1= mild pain, 2= moderate pain, 3= severe pain, or 4= extreme pain. |
| Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 24 Hours | Baseline (Day 1) to 24 hours | Participants were asked to complete a daily diary entry and assessed their pain in the past 24 hours using 5-point Likert Scale of 0 (None) to 4 (extreme pain), where; 0= none, 1= mild pain, 2= moderate pain, 3= severe pain, or 4= extreme pain. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 80 study sites in North America between 16 March 2009 and 26 February 2010. A total of 747 participants were screened in the study.
Pre-assignment details
Out of 747 participants, 225 were randomized and treated in the study. Participants were randomized in 1:1:1 ratio to receive one of the three treatment groups (Placebo \[for Rilonacept\] + Indomethacin or Rilonacept 320 mg + Indomethacin or Rilonacept 320 mg + Placebo \[for Indomethacin\]) on Day 1 of the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (for Rilonacept) and Indomethacin Two subcutaneous injections of Placebo (for Rilonacept) on Day 1 with Indomethacin orally TID for 12 days (Indomethacin 50 mg for first 3 days and then, Indomethacin 25 mg for next 9 days). | 75 |
| Rilonacept and Indomethacin Two subcutaneous injections of Rilonacept 160 mg (for a total of 320 mg) on Day 1 with Indomethacin orally TID for 12 days (Indomethacin 50 mg for first 3 days and then, Indomethacin 25 mg for next 9 days). | 74 |
| Rilonacept and Placebo (for Indomethacin) Two subcutaneous injections of Rilonacept 160 mg (for a total of 320 mg) on Day 1 with Placebo (for Indomethacin) orally TID for 12 days. | 73 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 1 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Decision by the sponsor | 0 | 1 | 1 |
| Overall Study | Lack of Efficacy | 2 | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 2 |
| Overall Study | Other than specified above | 1 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo (for Rilonacept) and Indomethacin | Rilonacept and Indomethacin | Rilonacept and Placebo (for Indomethacin) | Total |
|---|---|---|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 10.9 | 48.6 years STANDARD_DEVIATION 9.95 | 51.0 years STANDARD_DEVIATION 10.83 | 50.3 years STANDARD_DEVIATION 10.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 5 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants | 70 Participants | 68 Participants | 210 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 15 Participants | 11 Participants | 41 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 54 Participants | 54 Participants | 60 Participants | 168 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 71 Participants | 71 Participants | 67 Participants | 209 Participants |
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 | 8 / 77 | 7 / 73 | 7 / 75 |
| serious Total, serious adverse events | 0 / 77 | 3 / 73 | 0 / 75 |
Outcome results
Primary
Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint to Averaged PAP-LS at 24, 48 and 72 Hours
Participants were asked to complete a daily diary entry and assessed their pain in the past 24 hours using 5-point Likert Scale of 0 (None) to 4 (extreme pain), where; 0= none, 1= mild pain, 2= moderate pain, 3= severe pain, or 4= extreme pain. Change in PAP-LS in the index joint from baseline (Day 1) to the averaged PAP-LS values at 24, 48 and 72 hours was reported in this outcome measure (averaged PAP value= \[PAP at 24 hours + PAP at 48 hours + PAP at 72 hours\]/3).
Time frame: Pre-dose on Day 1 (Baseline); post-dose at 4, 8, 12, 24, 48, 72 hours and then daily up to Day 13 or until gout flare ends
Population: Full analysis set (FAS) that included of all randomized participants who received any study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (for Rilonacept) and Indomethacin | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint to Averaged PAP-LS at 24, 48 and 72 Hours | -1.40 units on a scale | Standard Deviation 0.956 |
| Rilonacept and Indomethacin | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint to Averaged PAP-LS at 24, 48 and 72 Hours | -1.55 units on a scale | Standard Deviation 0.919 |
| Rilonacept and Placebo (for Indomethacin) | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint to Averaged PAP-LS at 24, 48 and 72 Hours | -0.69 units on a scale | Standard Deviation 0.97 |
Secondary
Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 24 Hours
Participants were asked to complete a daily diary entry and assessed their pain in the past 24 hours using 5-point Likert Scale of 0 (None) to 4 (extreme pain), where; 0= none, 1= mild pain, 2= moderate pain, 3= severe pain, or 4= extreme pain.
Time frame: Baseline (Day 1) to 24 hours
Population: Full analysis set (FAS) that included all randomized participants who received any study drug and had at least 1 post-baseline assessment. Here, number of participants analyzed=participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (for Rilonacept) and Indomethacin | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 24 Hours | -1.16 units on a scale | Standard Deviation 1.021 |
| Rilonacept and Indomethacin | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 24 Hours | -1.44 units on a scale | Standard Deviation 0.895 |
| Rilonacept and Placebo (for Indomethacin) | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 24 Hours | -0.55 units on a scale | Standard Deviation 0.845 |
Secondary
Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 48 Hours
Participants were asked to complete a daily diary entry and assessed their pain in the past 24 hours using 5-point Likert Scale of 0 (None) to 4 (extreme pain), where; 0= none, 1= mild pain, 2= moderate pain, 3= severe pain, or 4= extreme pain.
Time frame: Baseline (Day 1) to 48 hours
Population: Full analysis set (FAS) that included all randomized participants who received any study drug and had at least 1 post-baseline assessment. Here, number of participants analyzed=participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (for Rilonacept) and Indomethacin | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 48 Hours | -1.36 units on a scale | Standard Deviation 0.883 |
| Rilonacept and Indomethacin | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 48 Hours | -1.54 units on a scale | Standard Deviation 0.959 |
| Rilonacept and Placebo (for Indomethacin) | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 48 Hours | -1.08 units on a scale | Standard Deviation 1.057 |
Secondary
Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 72 Hours
Participants were asked to complete a daily diary entry and assessed their pain in the past 24 hours using 5-point Likert Scale of 0 (None) to 4 (extreme pain), where; 0= none, 1= mild pain, 2= moderate pain, 3= severe pain, or 4= extreme pain.
Time frame: Baseline (Day 1) to 72 hours
Population: Full analysis set (FAS) that included all randomized participants who received any study drug and had at least 1 post-baseline assessment. Here, number of participants analyzed=participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (for Rilonacept) and Indomethacin | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 72 Hours | -1.41 units on a scale | Standard Deviation 0.865 |
| Rilonacept and Indomethacin | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 72 Hours | -1.57 units on a scale | Standard Deviation 1.104 |
| Rilonacept and Placebo (for Indomethacin) | Change From Baseline in Patient's Assessment of Pain Using a 5-Point Likert Scale (PAP-LS) in Index Joint at 72 Hours | -1.29 units on a scale | Standard Deviation 0.976 |