Canakinumab in the Treatment of Acute Gout Flares and Prevention of New Flares in Patients Unable to Use Non-steroidal Anti-inflammatory Drugs (NSAIDs) and/or Colchicines Including a 12 Week Extension and a 1 Year Open-label Extension Study.
- Conditions
- Acute Gout
- Interventions
- Registration Number
- NCT01080131
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this study was to demonstrate that canakinumab given upon acute gout flares relieves the signs and symptoms and prevents recurrence of gout flares in patients with frequent flares of gout for whom non-steroidal anti-inflammatory drugs (NSAIDs) and/ or colchicine are contraindicated, not tolerated, or ineffective. The efficacy of canakinumab was compared to the corticosteroid triamcinolone acetonide.
The purpose of the first 12 week extension study was to collect additional safety, tolerability and efficacy data in patients who have completed the core study CACZ885H2357.
The purpose of the second one year open-label extension study was to confirm the long-term safety and tolerability of canakinumab in patients who had completed the first extension study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 226
- Completion of the first extension study CACZ885H2357E1. A patient was defined as completing the first extension study if they completed the study up to and including Visit 10).
-Continuation in this second extension study was considered inappropriate by the treating physician.
Other protocol-defined inclusion-exclusion criteria applied to the core and extension studies.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Canakinumab 150 mg Canakinumab 150 mg Participants received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study. In the second extension study participants were to receive open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year, for a total duration of 18 months. Triamcinolone acetonide 40 mg Triamcinolone acetonide 40 mg Participants received 1 intramuscular (im) injection of triamcinolone acetonide 40 mg and 1 subcutaneous (sc) injection of placebo to canakinumab on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study. In the second extension study participants were to switch to open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year. Triamcinolone acetonide was not to be administered in the second extension study. Triamcinolone acetonide 40 mg Placebo to canakinumab Participants received 1 intramuscular (im) injection of triamcinolone acetonide 40 mg and 1 subcutaneous (sc) injection of placebo to canakinumab on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study. In the second extension study participants were to switch to open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year. Triamcinolone acetonide was not to be administered in the second extension study. Canakinumab 150 mg Placebo to triamcinolone acetonide Participants received 1 subcutaneous (sc) injection of canakinumab 150 mg and 1 intramuscular (im) injection of placebo to triamcinolone acetonide on Day 1. Participants could receive a re-dose of study drug on demand upon the occurrence of new flares, but re-dosing could not occur until 14 days had elapsed after the previous dose. Participants completing the 12 week core study could continue to be treated in a 12 week extension study for any new gout flare on demand with the same treatment as assigned in the core study. In the second extension study participants were to receive open-label on demand treatment with canakinumab 150 mg sc upon new flare for 1 year, for a total duration of 18 months.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events, Death and Serious Adverse Events (72 Weeks Overall) 72 weeks This was the primary endpoint of extension study 2. An adverse event was defined as any unfavorable and unintended diagnosis, symptom sign including an abnormal laboratory finding, syndrome or disease which either occurs during the study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS) at 72 Hours Post-dose 72 hours post-dose (randomization) Patients scored their pain intensity in the joint most affected at Baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100), at 72 hours post-dose. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The analysis of covariance (ANCOVA) analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates.
Time to First New Flare: Survival Analysis During the 12 Weeks of Study Baseline to 12 weeks Kaplan-Meier estimates of time to first new flare and confidence intervals were determined. For patients with event, time to event = (date of event - date of first dose of study drug + 1). Patients met definition of new flare if they had: •Flare in joint, not a previously affected joint (at baseline or during study) •Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely. Patients did not meet criterion of having new gout flare if: • Increasing/renewed gout pain in an affected joint before flare has resolved completely.
Number of Participants With Adverse Events, Death and Serious Adverse Events During 24 Weeks During 24 weeks overall This was primary endpoint of extension study 1. Adverse event is defined as any unfavorable and unintended diagnosis, symptom sign including an abnormal laboratory finding, syndrome or disease which either occurs during the study, having been absent at baseline, or, if present at baseline, appears to worsen. A serious adverse event is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
- Secondary Outcome Measures
Name Time Method Time to the First New Gout Flare During 24 Weeks From randomization to the end of the first extension period (24 weeks). Kaplan-Meier (KM) estimates of the time to first new flare and confidence intervals were determined. Participants met the definition of a new flare if they had:
* Flare in joint, not a previously affected joint (at baseline or during study)
* Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely.
Participants did not meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely.Time to Complete Resolution of Pain; Survival Analysis Baseline to 7 days post-dose (randomization) Kaplan-Meier estimates of the time to complete resolution of self-assessed pain intensity in the joint most affected and the confidence interval was determined. Patients scored their pain intensity on a 5-point Likert scale (none, mild, moderate, severe, extreme). Pain was scored at Baseline; 6 and 12 hours; 1, 2, 3, 4, 5, 6, and 7 days post-dose.
Percentage of Participants With at Least 1 New Gout Flare During the 12 Weeks of the Study Baseline to Week 12 The percentage of participants who experienced at least 1 new gout flare during the 12 week study treatment period.
Time to at Least a 50% Reduction in Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (VAS) Baseline to 7 days post-dose (randomization) Kaplan-Meier estimates of the time to at least a 50% reduction in self-assessed pain intensity in the joint most affected at Baseline and the confidence intervals were determined along with 95% confidence interval. Patients scored their pain intensity on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100). Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. Pain was scored at Baseline; at 6 and 12 hours post-dose; and at 1, 2, 3, 4, 5, 6, and 7 days post-dose.
Self-assessed Pain Intensity in the Joint Most Affected at Baseline Measured on a Visual Analog Scale (0-100 mm VAS) 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose (randomization) Patients scored their pain intensity in the joint most affected at Baseline on a 0-100 mm VAS, ranging from no pain (0) to unbearable pain (100), from 6 hours to 7 days post-dose. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The ANCOVA analysis included treatment group, Baseline VAS score, and body mass index (BMI) at Baseline as covariates.
Time to First Intake of Rescue Medication For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). Participants who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments as follows:
* Acetaminophen (paracetamol) 500 mg and/ or codeine 30 mg as required. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/ dose or 180 mg/day of codeine was allowed.
* If they had insufficient pain relief, participants were allowed to take a maximum of 30 mg of oral prednisolone as required per day for 2 days followed by up to 20 mg of prednisolone as required subsequent days within 7 days of a gout flare.
Use of these treatments during the first 7 days of a gout flare was recorded as rescue medication.
Kaplan-Meier estimates of the time to first intake of rescue medication, in hours, and the confidence interval were determined for the flare experienced at study entry (Baseline flare) and the last new flare (last post-baseline flare) that occurred up until the end of the first extension period (24 weeks).SF 36 Physical Function Score at Week 12 Week 12 SF-36 measures impact of disease on overall quality of life (QoL). 36-item survey has 8 subscales that can be aggregated into physical and mental component summary scores. Scores are standardized with the use of norm-based methods based on assessment of the general U.S. population free of chronic conditions. Scores range from 1-100 with a mean=50 and a standard deviation=10. A higher score indicates less impact on QoL. Analysis of covariance (ANCOVA) model was used with treatment group and baseline SF-36 physical function subscore as covariates.
Pharmacokinetic Concentrations 12 weeks post-dose Canakinumab concentration was analyzed in serum by means of a competitive Enzyme-linked immunosorbent assay (ELISA) assay with a lower limit of quantification (LOQ) at 100 ng/mL.
Self-assessed Pain Intensity in the Joint Most Affected at Last Post-Baseline Measured on a Visual Analog Scale (VAS) 6, 12, 24, 48, and 72 hours; and 4, 5, 6, and 7 days post-dose for last post-baseline flare that occurred up until the end of the first extension study (24 weeks). Patient's assessment of gout pain intensity in the most affected joint (on a 0-100 mm VAS) for the last post-baseline flare, ranging from no pain (0) to unbearable pain (100), was summarized up to 7 days after receiving a re-dose of study drug by time point. Scores on the 100 mm linear scale were measured to the nearest millimeter from the left. The covariance analysis included treatment group, Baseline VAS score at that flare, and body mass index (BMI) at Baseline as covariates.
Mean Number of New Gout Flares Per Patient During 24 Weeks 24 weeks Patients met definition of new flare if they had:
* Flare in joint, not a previously affected joint(at baseline or during study)
* Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely.
Participants did not meet the criterion of having a new gout flare if they had increasing/renewed gout pain in an affected joint before the flare had resolved completely.Percentage of Participants Who Took Rescue Medication For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). Participants who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments as follows:
* Acetaminophen (paracetamol) 500 mg and/ or codeine 30 mg as required. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/ dose or 180 mg/day of codeine was allowed.
* If they had insufficient pain relief, participants were allowed to take a maximum of 30 mg of oral prednisolone as required per day for 2 days followed by up to 20 mg of prednisolone as required subsequent days within 7 days of a gout flare.
Use of these treatments during the first 7 days of a gout flare was recorded as rescue medication.Amount of Rescue Medication Taken For 7 days after the first dose for the baseline flare and 7 days post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). Patients who had difficulty in tolerating their pain were allowed to take rescue medication after the 6-hour post-dose pain assessments as follows:
* Acetaminophen (paracetamol) 500 mg and/ or codeine 30 mg as required. A maximum of 1 g/dose or 3 g/day of acetaminophen and 30 mg/ dose or 180 mg/day of codeine was allowed.
* If they had insufficient pain relief, patients were allowed to take a maximum of 30 mg of oral prednisolone as required per day for 2 days followed by up to 20 mg of prednisolone as required subsequent days within 7 days of a gout flare.Physician's Global Assessment of Response to Treatment 72 hours post-dose and 24-weeks post-dose. The study physician made a global assessment of the patient's response to treatment using a 5-point Likert scale: Very good, good, fair, poor, very poor. The percentage of patients in each category is reported. The physician completed the assessment without viewing any of the patient's own assessments (pain intensity and patient's global assessment of response to treatment).
Patient's Global Assessment of Response to Treatment 72 hours post-dose and 24 weeks post-dose Participants made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight, poor. The percentage of participants in each category is reported.
Physician's Assessment of Tenderness, Swelling, and Erythema of the Most Affected Joint 72 hours post-dose and 24 weeks post-dose The study physician assessed the most affected joint for: Tenderness on a 0-3 point scale: No pain, patient states that "there is pain", patient states "there is pain and winces", and patient states "there is pain, winces, and withdraws" on palpation or passive movement of the affected study joint; Swelling on a 0-3 point scale: No swelling, palpable, visible, and bulging beyond the joint margins; and Erythema: Present or absent. The percentage of participants in each category is reported.
Physician's Assessment of Range of Motion of the Most Affected Joint 72 hours post-dose and 24 weeks post-dose The study physician assessed the range of motion of the most affected joint for range of motion on a 5-point Likert scale: Normal, mildly restricted, moderately restricted, severely restricted, immobilized. The percentage of participants in each category is reported.
High-sensitivity C-reactive Protein (hsCRP) and Serum Amyloid A Protein (SAA) Levels 72 hours after the first dose for the baseline flare and 72 hours post-dose for the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). High sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) were determined in blood serum in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment. Analyses were measured by a central laboratory. The analysis included treatment group, log-transformed protein level at baseline, and body mass index (BMI) at baseline as covariates.
Physician's Assessment of Erythema for Participants Re-treated or Switched to Canakinumab 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. The study physician assessed the most affected joint for erythema (redness of the skin) as either present, absent or not assessable.
Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.Serum Amyloid A Protein (SAA) Levels for Participants Re-treated With or Switched to Canakinumab 24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. Serum Amyloid A Protein (SAA) levels in blood serum were measured by a central laboratory in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment.
Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.Patient's Assessment of Gout Pain Intensity in the Most Affected Joint 72 hours post-dose and 24 weeks post-dose Participant scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe, extreme).
Percentage of Patients With Maximum Severity of New Gout Flares as Severe or Extreme From the onset of a new flare until re-dosing. First post-baseline new flare during 12 week core study and the last post-baseline flare that occurred up until the end of the first extension study (24 weeks). For each new flare, participants scored the maximum amount of acute gout pain in the most affected joint since the onset of the new flare and the time they were re-dosed on a 5 point Likert scale as None, Mild, Moderate, Severe or Extreme. The percentage of participants with a maximum new flare severity of severe or extreme is reported for the first post-baseline flare that occurred during the 12-week core study and for the last post-baseline flare that occurred up until the end of the first extension period.
Time to First New Flare: Survival Analysis by Treatment Over 72 Weeks From randomization to the end of the second extension period (72 weeks). Kaplan-Meier estimates of time to first new flare and confidence intervals were determined. For patients with event, time to event = (date of event - date of first dose of study drug + 1).
Patients met definition of new flare if they had:
* Flare in joint, not a previously affected joint (at baseline or during study)
* Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely.
Patients did not meet criterion of having new gout flare if:
• Increasing/renewed gout pain in an affected joint before flare has resolved completely.Flare Rate Per Year From randomization to the end of the second extension period (72 weeks). Flare rate was calculated as the number of new flares over the period of observation in years. Flare rate was calculated using only those new flares before switching to canakinumab.
Participants met the definition of new flare if they had:
* Flare in joint, not a previously affected joint (at baseline or during study)
* Flare in joint previously affected (at baseline or during study) after previous flare in joint has resolved completely.
Participants did not meet criterion of having new gout flare if:
• Increasing/renewed gout pain in an affected joint before the flare has resolved completely.
Flare rates were estimated from a negative binomial model with body mass index at baseline as a covariate.Patient's Assessment of Gout Pain Intensity for Participants Re-treated or Switched to Canakinumab 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. Participants scored their current pain intensity in the most affected joint of the gout flare on a 5-point Likert Scale (none, mild, moderate, severe or extreme).
Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.Patient's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. Participants made a global assessment of response to treatment using a 5-point Likert scale: Excellent, good, acceptable, slight or poor. Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.
Physician's Global Assessment of Response to Treatment for Participants Re-treated or Switched to Canakinumab 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. The study physician made a global assessment of the patient's response to treatment using a 5-point Likert scale: very good, good, fair, poor or very poor.
The physician completed the physician's global assessment of response to treatment without viewing any of the patient's assessments.
Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.Physician's Assessment of Joint Tenderness for Participants Re-treated or Switched to Canakinumab 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. The study physician assessed the most affected joint for tenderness on the following 4-point scale:
* no pain;
* participant states that "there is pain;
* participant states "there is pain and winces";
* participant states "there is pain, winces and withdraws" on palpation or passive movement of the affected study joint.
Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.Physician's Assessment of Joint Swelling for Participants Re-treated or Switched to Canakinumab 72 hours post-dose and 7 days post dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. The study physician assessed the most affected joint for swelling on the following 4-point scale:
* no swelling;
* palpable;
* visible;
* bulging beyond the joint margins.
Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.High-sensitivity C-reactive Protein (hsCRP) Levels for Participants Re-treated With or Switched to Canakinumab 24 hours, 72 hours, 7 days, 4, 8 and 12 weeks post-dose for the last post-baseline flare for the canakinumab re-treated arm and for the first post-baseline flare treated with canakinumab in the triamcinolone acetonide arm during the overall 72 weeks. High sensitivity C-reactive protein (hsCRP) levels in blood serum were measured by a central laboratory in order to identify the presence of inflammation, to determine its severity, and to monitor the response to treatment.
Data are reported for the last post-baseline flare for participants who were randomized to and re-treated with canakinumab, and for the first post-baseline flare treated with canakinumab for participants randomized to triamcinolone acetonide and who were switched to canakinumab in extension study 2.
Trial Locations
- Locations (95)
Crest Clinical Trials
🇺🇸Santa Ana, California, United States
Rheumatic Disease Clinical Research Center, Llc
🇺🇸Houston, Texas, United States
Rochester clinical Research
🇺🇸San Diego, California, United States
Arthritis Center South Texas
🇺🇸San Antonio, Texas, United States
Wichita Clinic
🇺🇸Wichita, Kansas, United States
Pinnacle Medical Research
🇺🇸Overland Park, Kansas, United States
Pinnacle Research Group, LLC
🇺🇸Anniston, Alabama, United States
Valerius Medical Group and Research Center of Long Branch
🇺🇸Long Beach, California, United States
Providence Research
🇺🇸Burbank, California, United States
Chaparral Medical Grp, INC Clinical Research
🇺🇸Pomona, California, United States
Arthritis Associates
🇺🇸San Antonio, California, United States
Innovative Research of West Florida
🇺🇸Clearwater, Florida, United States
Med Investigations
🇺🇸Fair Oaks, California, United States
California Research Foundation
🇺🇸San Diego, California, United States
Horizon Research Group, Inc.
🇺🇸Mobile, Alabama, United States
Health Awareness
🇺🇸Jupiter, Florida, United States
Progressive Clinical Research
🇺🇸Vista, California, United States
Sierra Clinical Research
🇺🇸Orangevale, California, United States
Q Clinical Research
🇺🇸Decatur, Georgia, United States
Huntington Medical Foundation
🇺🇸San Marino, California, United States
DMI Healthcare Group, Inc.
🇺🇸Pinellas Park, Florida, United States
Ritchken and First MDs
🇺🇸San Diego, California, United States
L Kage Healthcare Services
🇺🇸Flint, Michigan, United States
The Arthritis Center
🇺🇸Springfield, Illinois, United States
Metrolina Medical Research
🇺🇸Charlotte, North Carolina, United States
Andrew J. Porges, MD, PC
🇺🇸Roslyn, New York, United States
MASS Research, LLC
🇺🇸Waltham, Massachusetts, United States
Oakland Medical Research Center
🇺🇸Troy, Michigan, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Health Research Institute
🇺🇸Oklahoma City, Oklahoma, United States
Tampa Medical Group, P.A.
🇺🇸Tampa, Florida, United States
RST DAta Research
🇺🇸Conyers, Georgia, United States
Diagnamics, Inc.
🇺🇸Carlsbad, California, United States
Sun Valley Arthritis Center, Ltd
🇺🇸Peoria, Arizona, United States
Lucita M. Cruz, M.D., Inc.
🇺🇸Norwalk, California, United States
Genova Clinical Research
🇺🇸Tucson, Arizona, United States
Center for Clinical Trials of San Gabriel
🇺🇸West Covina, California, United States
Orange County Research Center
🇺🇸Tustin, California, United States
Deaconess Clinic
🇺🇸Evansville, Indiana, United States
Pines Research, LLC Pembroke Clinical Trials
🇺🇸Pembroke Pines, Florida, United States
Gulf Coast Research, LLC
🇺🇸Lafayette, Louisiana, United States
Dolby Research, LLC
🇺🇸Baton Rouge, Louisiana, United States
Arthritis and Diabetes Clinic
🇺🇸Monroe, Louisiana, United States
*Private Practice*
🇺🇸Lansing, Michigan, United States
Clarkston Medical Group
🇺🇸Clarkston, Michigan, United States
Phillips Medical Center
🇺🇸Jackson, Mississippi, United States
West Michigan Rheumatology
🇺🇸Grand Rapids, Michigan, United States
Arthritis and Osteoporosis Medical Association
🇺🇸Brooklyn, New York, United States
The Center For Nutrition and Preventive Medicine
🇺🇸Charlotte, North Carolina, United States
Columbia Arthritis Center
🇺🇸Columbus, Ohio, United States
STAT Research, Inc.
🇺🇸Dayton, Ohio, United States
Humility of Mary Health Partners DBA St. Elizabeth Health Ce
🇺🇸Youngstown, Ohio, United States
Health Research of Oklahoma, PLLC
🇺🇸Oklahoma City, Oklahoma, United States
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Partners in Clinical Research
🇺🇸Bumberland, Rhode Island, United States
Palmetto Clinical Trial Services, LLC
🇺🇸Greenville, South Carolina, United States
Tlm Medical Services Llc
🇺🇸Columbia, South Carolina, United States
Tri-Cities Medical Research
🇺🇸Bristol, Tennessee, United States
The Jackson Clinic
🇺🇸Jackson, Tennessee, United States
The Arthritis Clinic
🇺🇸Jackson, Tennessee, United States
MultiSpecialty Clinical Research
🇺🇸Johnson City, Tennessee, United States
R/D Clinical Research, Inc.
🇺🇸Lake Jackson, Texas, United States
Leander Healthcare Center
🇺🇸Leander, Texas, United States
North Hills Family Practice
🇺🇸North Richard Hills, Texas, United States
Novartis Investigative Site
🇷🇺Yekaterinburg, Russian Federation
Health Research of Hampton Roads
🇺🇸Newport News, Virginia, United States
Unifour Medical Research Associates
🇺🇸Hickory, North Carolina, United States
Ohio Clinical Research, LLC
🇺🇸Willoughby Hills, Ohio, United States
Philadelphia VA medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Accurate Clinical Research
🇺🇸Nassau Bay, Texas, United States
Sonora Clinical Research, LLC
🇺🇸Boise, Idaho, United States
Regional Research Specialists
🇺🇸Shreveport, Louisiana, United States
Clinical Research Advantage, Inc
🇺🇸Henderson, Nevada, United States
CRC of Jackson
🇺🇸Jackson, Mississippi, United States
Montana Medical Research
🇺🇸Missoula, Montana, United States
Novartis Investigative site
🇳🇱Leeuwarden, Netherlands
UMDNJ Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Clinical Res Ct of CT - Arthritis Associates of CT/NY, LLC
🇺🇸Danbury, Connecticut, United States
Quality Clinical Research
🇺🇸Omaha, Nebraska, United States
Heartland Clinical Research, Inc.
🇺🇸Omaha, Nebraska, United States
Northwest Clinical Trials
🇺🇸Boise, Idaho, United States
The Family Doctors
🇺🇸Shreveport, Louisiana, United States
Arthritis Associates of Mississippi
🇺🇸Jackson, Mississippi, United States
Little Rock Diagnostic Clinic
🇺🇸Little Rock, Arkansas, United States
Clinical Trials Management
🇺🇸Metairie, Louisiana, United States
Arthritis and Osteoporosis Associates
🇺🇸Freehold, New Jersey, United States
Alpha Clinical Research
🇺🇸Clarksville, Tennessee, United States
Community Research Partners, Inc.
🇺🇸Varnville, South Carolina, United States
River City Clinical Research
🇺🇸Sacramento, California, United States
Medical Research South
🇺🇸Charleston, South Carolina, United States
Pharmacorp Clinical Trials, INC
🇺🇸Charleston, South Carolina, United States
Lovelace Scientific Resource
🇺🇸Austin, Texas, United States
Center for Rheumatology & Bone Research
🇺🇸Wheaton, Maryland, United States
Harbin Clinic
🇺🇸Rome, Georgia, United States
Jones Family Practice, PA
🇺🇸Shelby, North Carolina, United States