MedPath

A Long-Term, Placebo-Controlled X-Ray Study Investigating the Safety and Efficacy of SD-6010 in Subjects With Osteoarthritis of the Knee

Phase 2
Completed
Conditions
Osteoarthritis
Interventions
Drug: SD-6010
Drug: Placebo
Registration Number
NCT00565812
Lead Sponsor
Pfizer
Brief Summary

The objective of this 2-year study is to evaluate the safety, tolerability and disease modifying efficacy of SD 6010, an inhibitor of inducible nitric oxide synthase (iNOS), in overweight and obese subjects with knee osteoarthritis. The efficacy of SD-6010 will be evaluated by radiography using joint space narrowing in the medial tibiofemoral compartment of the study knee as the primary endpoint.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1457
Inclusion Criteria
  • Subjects aged >= 40 years with a BMI >= 25 and <= 40 kg/m2
  • In the past, has been diagnosed with knee OA
  • Radiographic evidence of OA in the study knee
Read More
Exclusion Criteria
  • A diagnosis of any other rheumatic disease
  • Current conditions in the study knee that would confound efficacy
  • Selected, traditional clinical safety and laboratory parameters
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
200 mgSD-6010High dose active comparator
50 mgSD-6010Low dose active comparator
PlaceboPlaceboPlacebo comparator to be used for control purposes
Primary Outcome Measures
NameTimeMethod
Rate of Progression of Joint Space NarrowingBaseline up to Month 24

Rate of progression of joint space narrowing (JSN) was defined as narrowing in joint space width (JSW) over the course of the study. It was measured radiographically in the medial tibiofemoral of knee of participants with OA. The slope reported in millimeter per year (mm/year) over a 2 year period was used to assess the rate of progression of JSN. Negative values indicating a worsening of osteoarthritis.

Rate of Progression of Joint Space Narrowing in Participants With Kellgren and Lawrence Grade Less Than or Equal to (<=) 2Baseline up to Month 24

Rate of progression of JSN was defined as narrowing in joint space width over the course of the study. It was measured radiographically in the medial tibiofemoral of knee of participants with OA. The slope reported in mm/year over a 2 year period was used to assess the rate of progression of JSN. KLG system was a method of classifying the severity of knee OA using five grades (0 \[no severity\] to 4 \[maximum severity\], higher grade indicating worse knee function). Negative values of slope indicating a worsening of osteoarthritis.

Rate of Progression of Joint Space Narrowing in Participants With Kellgren and Lawrence Grade Equal to (=) 3Baseline up to Month 24

Rate of progression of JSN was defined as narrowing in joint space width over the course of the study. It was measured radiographically in the medial tibiofemoral of knee of participants with OA. The slope reported in mm/year over a 2 year period was used to assess the rate of progression of JSN. KLG system was a method of classifying the severity of knee OA using five grades (0 \[no severity\] to 4 \[maximum severity\], higher grade indicating worse knee function). Negative values of slope indicating a worsening of osteoarthritis.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index (WOMAC) Composite Index Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

The WOMAC was a self-administered, disease-specific instrument which probed clinically important, participant relevant symptoms in the areas of pain, stiffness, and physical function in participants with OA of the knee. The WOMAC composite index was the sum of 24 individual questions regarding subscales of pain, stiffness and physical function (for each item score range: 0 \[minimum\] to 4 \[maximum\], higher score indicating worse knee condition). Total score was sum of the 3 subscale scores, giving a possible overall score range of 0 (minimum) to 96 (maximum). Higher score indicating the worse level of pain, stiffness and physical function.

Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Pain Subscale Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

The WOMAC pain subscale was comprised of 5 questions regarding the amount of pain experienced due to OA in the study knee. The WOMAC pain subscale score for each question ranged from 0 (minimum) to 4 (maximum), higher scores signified worse pain. An overall subscale score range of 0 (minimum) to 20 (maximum), with higher scores indicating more pain.

Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Pain Stiffness Subscale Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

Stiffness was defined as a sensation of decreased ease in which the participant moved the knee with OA. The WOMAC stiffness subscale was comprised of 2 questions regarding the degree of stiffness experienced in the study knee. The WOMAC stiffness subscale score for each question ranged from 0 (minimum) to 4 (maximum), higher scores signified worse stiffness. An overall score range of 0 (minimum) to 8 (maximum), with higher scores indicating more stiffness.

Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Physical Function Subscale Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

The WOMAC physical function subscale referred to the participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was comprised of 17 questions regarding the degree of difficulty experienced due to OA in the study knee. The WOMAC physical function subscale score for each question ranged from 0 (minimum) to 4 (maximum), higher scores signified worse physical function. An overall score range of 0 (minimum) to 68 (maximum), with higher scores indicating worse physical function.

Change From Baseline in Patient Assessment of Arthritic Pain Visual Analog Scale (VAS) Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

Pain VAS was a self-administered instrument, a 100 millimeter (mm) line marked by participant. Intensity of pain range (over past week): 0 (mm) =no pain to 100 (mm) =worst possible pain. Higher score indicating severe pain.

Change From Baseline in Patient Global Assessment of Arthritic Condition Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using the scale ranging from 1 (minimum) to 5 (maximum), where 1 =very good, 2 =good, 3 =fair, 4 =poor and 5 =very poor. Higher scores indicating worse condition.

Change From Baseline in Physician's Global Assessment of Arthritic Condition Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

Physician assessed the overall impact of arthritis on the participant's daily life. Participant's condition was rated by the physician using the scale ranging from 1 (minimum) to 5 (maximum), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicating worse condition.

Change From Baseline in Pain After a 50-foot Walk Using Pain Visual Analog Scale Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

The pain VAS following a 50 foot walk was a single-item, self-administered instrument. Participants were asked to assess the pain due to OA in their study knee after a 50-foot walk. Participants responded on a VAS scale ranging from 0 (no pain) to 100 (severe pain). Higher scores indicating more pain.

Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Total Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

The OA pain and assessment tool-knee joint is also known as the intermittent and constant osteoarthritis pain (ICOAP) scale. The OA pain assessment tool-knee joint was an 11-item scale, with each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. The total score was calculated by adding the 11 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse health.

Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Constant Pain Subscale Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

The OA pain assessment tool-knee joint constant pain subscale was a 5 item scale, with each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. Overall subscale score was calculated by adding the 5 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse constant pain.

Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Intermittent Pain Subscale Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

The OA pain assessment tool-knee joint intermittent pain subscale score a 6 item scale, with each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. Overall subscale score was calculated by adding the 6 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse intermittent pain.

Change From Baseline in Osteoarthritis Research Society International (OARSI) Knee Function Survey Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

The OARSI knee function survey was an 11-item scale with each item scored 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. The total score was the sum of the 11 items and ranged from 0 (minimum) to 44 (maximum), where higher scores indicating worse health condition.

Change From Baseline in Knee Injury and Osteoarthritis Outcome Score - Physical Function Short Form (KOOS-PS) Score at Month 3, 6, 12, 18 and 24Baseline, Month 3, 6, 12, 18, 24

The KOOS-PS was used to rate participant's opinions about the difficulties they experienced with activity due to problems with their knee. It was a 7-item scale, each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. Total score was calculated by adding the responses to 7 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse health condition.

Change From Baseline in Short Form-36 (SF-36) Physical Functioning Domain Score at Month 12 and 24Baseline, Month 12, 24

The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 16.18 (minimum) to 57.11 (maximum), with higher scores indicating better physical functioning.

Change From Baseline in Short Form-36 Role - Physical Domain Score at Month 12 and 24Baseline, Month 12, 24

The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 18.45 (minimum) to 56.62 (maximum), with higher scores indicating better role-physical.

Change From Baseline in Short Form-36 Role-Emotional Domain Score at Month 12 and 24Baseline, Month 12, 24

The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 10.25 (minimum) to 55.68 (maximum), with higher scores indicating better role-emotional.

Change From Baseline in Short Form-36 Mental Health Domain Score at Month 12 and 24Baseline, Month 12, 24

The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 8.02 (minimum) to 63.43 (maximum), with higher scores indicating better mental health.

Change From Baseline in Short Form-36 Bodily Pain Domain Score at Month 12 and 24Baseline, Month 12, 24

The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 19.23 (minimum) to 60.88 (maximum), with higher scores indicating lower bodily pain.

Change From Baseline in Short Form-36 General Health Domain Score at Month 12 and 24Baseline, Month 12, 24

The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 16.75 (minimum) to 63.72 (maximum), with higher scores indicating better general health.

Number of Participants With Joint Space Narrowing ProgressionMonth 24

JSN progressor was defined as a participant with a decrease in joint space width that was greater in magnitude than the smallest detectable difference (0.199 mm).

Number of Participants Applicable for Virtual Joint ReplacementMonth 24

A virtual joint replacement candidate was defined as a participant whose last two WOMAC pain subscale scores (overall score range of 0 \[minimum\] to 20 \[maximum\], higher scores indicating more pain) were at least 8, last two WOMAC physical function subscale scores (overall score range of 0 \[minimum\] to 68 \[maximum\], higher scores indicating worse physical function) were at least 28 and was a joint space narrowing progressor (a participant with a decrease in JSW that was greater in magnitude than the smallest detectable difference =0.199 mm).

Change From Baseline in Short Form-36 Vitality Domain Score at Month 12 and 24Baseline, Month 12, 24

The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 22.02 (minimum) to 69.92 (maximum), with higher scores indicating better vitality.

Change From Baseline in Short Form-36 Social Functioning Domain Score at Month 12 and 24Baseline, Month 12, 24

The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 13.38 (minimum) to 56.40 (maximum), with higher scores indicating better social functioning.

Change From Baseline in Short Form-36 Mental Health Component Score at Month 12 and 24Baseline, Month 12, 24

The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 11.11 (minimum) to 61.67 (maximum), with higher scores indicating better mental health.

Number of Participants With EuroQoL-5D Self-Care Domain ScoreBaseline, Month 12, 24

EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D self-care domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no problems with self-care), 2 =moderate health (some problems) and 3 =worst health (unable to wash or dress). Higher scores indicating worse health condition. Participants with EQ-5D self-care domain score were reported in this measure.

Number of Participants With EuroQoL-5D Usual Activity Domain ScoreBaseline, Month 12, 24

EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D usual activity domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no problems), 2 =moderate health (some problems) and 3 =worst health state (unable to perform usual activities). Higher scores indicating worse health condition. Participants with EQ-5D usual activity domain score were reported in this measure.

Number of Participants With EuroQo-5D Pain and Discomfort Domain ScoreBaseline, Month 12, 24

EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D pain and discomfort domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no pain and discomfort), 2 =moderate health (moderate pain and discomfort) and 3 =worst health state (extreme pain and discomfort). Higher scores indicated worse health condition. Participants with EQ-5D pain and discomfort domain score were reported in this measure.

Number of Participants With EuroQoL-5D Anxiety and Depression Domain ScoreBaseline, Month 12, 24

EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. EQ-5D anxiety and depression domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (not anxious, depressed), 2 =moderate health (moderately anxious, depressed) and 3 =worst health (extremely anxious, depressed). Higher scores indicating worse health condition. Participants with EQ-5D anxiety and depression domain score were reported in this measure.

EuroQoL-5D Visual Analog Scale ScoreBaseline, Month 12, 24

The EQ-5D VAS score was a participant rated questionnaire to assess health-related quality of life in terms of a single index value. It was a visual analogue scale that ranged from 0 (minimum) to 100 (maximum), with higher scores indicating a better health condition.

Number of Participants With Increase in Total Analgesic Medication UseMonth 12, 24

Increase in total analgesic medication use for OA in the study knee was a comparison back to baseline of an increased and sustained use of standard background and/or rescue medication for more than 28 days as measured at the Month 12 and 24 visits. Only medications for OA knee pain were considered.

Number of Participants With Decrease in Total Analgesic Medication UseMonth 12, 24

Decrease in total analgesic medication use for OA in the study knee was a comparison back to baseline of a decreased and irregular use of standard background and/or rescue medication for more than 28 days as measured at the Month 12 and 24 visits. Only medications for OA knee pain were considered.

Change From Baseline in Short Form-36 Physical Health Component Score at Month 12 and 24Baseline, Month 12, 24

The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 22.88 (minimum) to 58.69 (maximum), with higher scores indicating better physical health.

Number of Participants With EuroQoL-5D (EQ-5D) Mobility Domain ScoreBaseline, Month 12, 24

EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D mobility domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no problem), 2 =moderate health (some problems) and 3 =worst health (confined to bed). Higher scores indicating worse health condition. Participants with EQ-5D mobility domain score were reported in this measure.

Patient Global Impression of Change ScoreMonth 24

Patient global impression of change was a participant-rated instrument that measured change in participant's overall status on a 7-point scale ranging from: 1 =very much improved, 2 =much improved, 3 =minimally improved, 4 =no change, 5 =minimally worse, 6 =much worse and 7 =very much worse. Higher scores indicating worse condition.

Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Responder IndexMonth 24

The OMERACT-OARSI responder index was used to determine whether participants may be considered responders to treatment. An OMERACT-OARSI responder was a participant who had a better response on the WOMAC pain subscale score, a better response on the WOMAC physical function subscale score or improvement on at least two of the three domains: WOMAC pain subscale score (overall score range of 0 \[minimum\] to 20 \[maximum\], higher scores indicating more pain), WOMAC physical function subscale score (overall score range of 0 \[minimum\] to 68 \[maximum\], higher scores indicating worse physical function) and patient global assessment of arthritic condition score (overall score range of 1 \[minimum\] to 5 \[maximum\], higher scores indicating worse condition). Number of participants who were OMERACT-OARSI responder were reported in this measure.

Trial Locations

Locations (172)

Plaza Medical Imaging

🇺🇸

Santa Ana, California, United States

Rapid Medical Research, Inc.

🇺🇸

Cleveland, Ohio, United States

The Center for Rheumatology and Bone Research

🇺🇸

Wheaton, Maryland, United States

Universitair Ziekenhuis Gasthuisberg / Rheumatology

🇧🇪

Leuven, Belgium

Centrum pro zdravotnicke zabezpeceni sportovni reprezentace

🇨🇿

Praha 6, Czech Republic

ARTMEDI UPD s r.o.

🇨🇿

Hostivice, Czech Republic

MSI - Muskuloskeletalni institut

🇨🇿

Praha 6, Czech Republic

MediCentrum Praha, a.s.

🇨🇿

Praha 11 - Chodov, Czech Republic

V. Interna klinika FN a LF UK

🇸🇰

Bratislava, Slovakia

Ivan Ujvari

🇸🇰

Bratislava, Slovakia

Narodny ustav reumatickych chorob

🇸🇰

Piestany, Slovakia

MEDIPONT, s.r.o.

🇨🇿

Ceske Budejovice, Czech Republic

Hospital Maria Auxiliadora

🇵🇪

Lima, Peru

University of Arizona

🇺🇸

Tucson, Arizona, United States

Arizona Research Center

🇺🇸

Phoenix, Arizona, United States

Scripps Clinic-Clinical Research

🇺🇸

San Diego, California, United States

Affiliated Clinical Research, Inc.

🇺🇸

Las Vegas, Nevada, United States

Office of Michael Mall, M.D.

🇺🇸

Las Vegas, Nevada, United States

Radiant Research San Antonio Northeast

🇺🇸

San Antonio, Texas, United States

South Texas Radiology Imaging Center

🇺🇸

San Antonio, Texas, United States

Revmacentrum MUDr. Mostera, s.r.o.

🇨🇿

Brno - Zidenice, Czech Republic

Nemocnice Na Frantisku s poliklinikou

🇨🇿

Praha 1, Czech Republic

Revmatologicky ustav

🇨🇿

Praha 2, Czech Republic

DC Mediscan

🇨🇿

Praha 11 - Chodov, Czech Republic

PV-Medical s.r.o.

🇨🇿

Zlin, Czech Republic

Centro Empresarial - Altavista Polo 4

🇵🇪

Santiago de Surco, Lima, Peru

Praxis Dr. Thomas Jung

🇩🇪

Deggingen, Germany

Ospedale Luigi Sacco, Azienda Ospedaliera Polo Universitario Unita' Operativa di Reumatologia

🇮🇹

Milano, Italy

NSZOZ "MEDICUS II" S.C. Irena Klimczak, Malgorzata Klimczak, Jerzy Klimczak

🇵🇱

Cieszyn, Poland

Nemocnice Atlas, a.s.

🇨🇿

Zlin, Czech Republic

Praxis fuer Orthopaedie

🇩🇪

Berlin, Germany

Bekes Megyei Kepviselo-testulet Pandy Kalman Korhaz, Reumatologia

🇭🇺

Gyula, Hungary

Hospital Nacional "Alberto Sabogal Sologuren" - Essalud

🇵🇪

Callao, Peru

Orszagos Gerincgyogyaszati Kozpont

🇭🇺

Budapest, Hungary

Selye Janos Korhaz, Reumatologiai Szakrendelo

🇭🇺

Komarom, Hungary

Azienda Sanitaria Genovese, Ospedale La Colletta, Dipartimento Apparato Locomotore

🇮🇹

Arenzano, Italy

Hospital Nacional "Edgardo Rebagliati Martins" - Essalud

🇵🇪

Lima, Peru

Katedra i Klinika Ortopedii i Traumatologii Narzadu Ruchu

🇵🇱

Wroclaw, Poland

Presidio Ospedaliero Augusto Murri, Reparto di Reumatologia

🇮🇹

Jesi (Ancona), Italy

Instituto de Ginecologia y Reproducción & Cirugia Minimamente Invasiva

🇵🇪

Santiago de Surco, Lima, Peru

Clínica San Felipe

🇵🇪

Lima, Peru

Instituto Peruano del Hueso y la Articulación SAC.

🇵🇪

Lima, Peru

Research Institute of Traumatology and Orthopedy Named After R. R. Vredena

🇷🇺

St. Petersburg, Russian Federation

Hospital General Universitario de Guadalajara

🇪🇸

Guadalajara, Spain

Centro Medico Corpac

🇵🇪

Lima, Peru

"SYNEXUS SCM" Sp. z o.o.

🇵🇱

Wroclaw, Poland

L.G. Sokolov Clinical Hospital #122 of Federal Medical-Biology Agency of Russia, Central Polyclinic

🇷🇺

St. Petersburg, Russian Federation

Hospital Ntra. Sra. de La Esperanza

🇪🇸

Santiago de Compostela, A Coruña, Spain

Centre de Rhumatologie St-Louis

🇨🇦

Sainte-Foy, Quebec, Canada

Med Center

🇺🇸

Carmichael, California, United States

Gold Coast Research, LLC

🇺🇸

Plantation, Florida, United States

Sabiha Khan, M.D.

🇺🇸

Plantation, Florida, United States

Med Investigations, Inc.

🇺🇸

Fair Oaks, California, United States

Teton Research, LLC

🇺🇸

Little Rock, Arkansas, United States

Greystone Medical Center

🇺🇸

Birmingham, Alabama, United States

Pivotal Research Centers

🇺🇸

Midvale, Utah, United States

College Hospital Costa Mesa

🇺🇸

Costa Mesa, California, United States

Advanced Radiology Consultants

🇺🇸

Stamford, Connecticut, United States

Kanner, Mendelson, Shteinman, LLC

🇺🇸

West Palm Beach, Florida, United States

MedVadis Research Corporation

🇺🇸

Wellesley Hills, Massachusetts, United States

L-MARC Research Center

🇺🇸

Louisville, Kentucky, United States

HCI Metromedic Walk-In

🇺🇸

New Bedford, Massachusetts, United States

Cadillac Clinical Research, LLC, located at Great Lakes Family Care

🇺🇸

Cadillac, Michigan, United States

TFD Research, LLC

🇺🇸

Shreveport, Louisiana, United States

North Georgia Clinical Research

🇺🇸

Woodstock, Georgia, United States

NorthShore University HealthSystem

🇺🇸

Vernon Hills, Illinois, United States

Fall River Clinical Research

🇺🇸

Fall River, Massachusetts, United States

Fallon Clinic, Inc.

🇺🇸

Worcester, Massachusetts, United States

Dynamic Clinical Research, Inc.

🇺🇸

Kansas City, Missouri, United States

Phase III Clinical Research

🇺🇸

Fall River, Massachusetts, United States

Office of Manoj Kohli, M.D.

🇺🇸

Lexington, Kentucky, United States

Joan Prouty Moore, MD

🇺🇸

Kansas City, Missouri, United States

Fallon Clinic, Inc. (Drug Shipment)

🇺🇸

Worcester, Massachusetts, United States

Arthritis and Osteoporosis Treatment and Research Center

🇺🇸

Flowood, Mississippi, United States

VirtualScopics, Inc.

🇺🇸

Rochester, New York, United States

North Mississippi Medical Center, Inc.

🇺🇸

Tupelo, Mississippi, United States

Nevada Imaging Centers

🇺🇸

Las Vegas, Nevada, United States

The Center for Pharmaceutical Research, P.C.

🇺🇸

Kansas City, Missouri, United States

Office of Stephen H. Miller, MD

🇺🇸

Las Vegas, Nevada, United States

PMG Research of Wilmington, LLC

🇺🇸

Wilmington, North Carolina, United States

Crouse Medical Practice, PLLC d/b/a Internist Associates of Central New York

🇺🇸

Syracuse, New York, United States

Lillestol Research, LLC

🇺🇸

Fargo, North Dakota, United States

Southeastern Radiology

🇺🇸

Greensboro, North Carolina, United States

Kernodle Clinic Inc.

🇺🇸

Burlington, North Carolina, United States

D. Matthew Sellers MD PC

🇺🇸

Knoxville, Tennessee, United States

PMG Research of Salisbury

🇺🇸

Salisbury, North Carolina, United States

Baylor Research Institute

🇺🇸

Dallas, Texas, United States

Internal Medicine Associates

🇺🇸

Fargo, North Dakota, United States

Advanced Pain Management

🇺🇸

Virginia Beach, Virginia, United States

National Clinical Research - Norfolk, Inc.

🇺🇸

Norfolk, Virginia, United States

OMI - Organización Médica de Investigación

🇦🇷

Buenos Aires, Argentina

Holston Medical Group

🇺🇸

Kingsport, Tennessee, United States

Tacoma Center for Arthritis Research, PS

🇺🇸

Tacoma, Washington, United States

Oakwell Clinical Research, LLC

🇺🇸

San Antonio, Texas, United States

Cliniques Universitaires St Luc

🇧🇪

Bruxelles, Belgium

Metroplex Clinical Research Center

🇺🇸

Dallas, Texas, United States

The Arthritis Program Research Group Inc.

🇨🇦

Newmarket, Ontario, Canada

MEDIPONT Plus, s.r.o.

🇨🇿

Ceske Budejovice, Czech Republic

Klinische Forschung Berlin-Buch

🇩🇪

Berlin, Germany

Menzies Research Institute

🇦🇺

Hobart, Tasmania, Australia

Rheumatology Research Associates Ltd.

🇨🇦

Edmonton, Alberta, Canada

Nexus Clinic Research

🇨🇦

St. John's, Newfoundland and Labrador, Canada

Fakultni nemocnice u sv. Anny v Brne

🇨🇿

Brno, Czech Republic

Orthopaedic and Occupational Medicine

🇺🇸

Kansas City, Missouri, United States

Russian State Medical University, Moscow Faculty, City Clinical Hospital #4

🇷🇺

Moscow, Russian Federation

Institute of Rheumatology

🇷🇺

Moscow, Russian Federation

Praxis fuer Orthopaedie, Chirotherapie und Akupunktur

🇩🇪

Bad Hersfeld, Germany

Klinische Forschung Schwerin

🇩🇪

Schwerin, Germany

Synexus Magyarorszag Kft.

🇭🇺

Budapest, Hungary

Veszprem Megyei Onkormanyzat Csolnoky Ferenc Korhaz-Rendelointezet

🇭🇺

Veszprem, Hungary

MAV Korhaz es Rendelointezet

🇭🇺

Szolnok, Hungary

Instituto Médico Especializado (IME)

🇦🇷

Buenos Aires, Argentina

IMAI Research

🇦🇷

Buenos Aires, Argentina

University of California Davis Health System

🇺🇸

Sacramento, California, United States

University of California Davis

🇺🇸

Sacramento, California, United States

Denver Internal Medicine Group

🇺🇸

Denver, Colorado, United States

Mountain View Clinical Research, Inc.

🇺🇸

Denver, Colorado, United States

Southeastern Arthritis Center

🇺🇸

Gainesville, Florida, United States

Heves Megyei Onkormanyzat Markhot Ferenc Korhaz

🇭🇺

Eger, Hungary

Brookwood Internists, P.C.

🇺🇸

Birmingham, Alabama, United States

NeuroNetwork Trials

🇺🇸

Costa Mesa, California, United States

Sierra Clinical Research

🇺🇸

Roseville, California, United States

New West Physicians Clinical Research

🇺🇸

Golden, Colorado, United States

Stamford Therapeutics Consortium

🇺🇸

Stamford, Connecticut, United States

New England Research Associates, LLC

🇺🇸

Trumbull, Connecticut, United States

Jacksonville Center for Clincal Research

🇺🇸

Jacksonville, Florida, United States

Southeastern Imaging & Diagnostics

🇺🇸

Gainesville, Florida, United States

Southeastern Integrated Medical, PL, d/b/a Florida Medical Research Institute

🇺🇸

Gainesville, Florida, United States

Memorial Hospital Jacksonville

🇺🇸

Jacksonville, Florida, United States

Marin E. Hale, M.D., P.A.

🇺🇸

Plantation, Florida, United States

Rheumatology and Endocrinology Specialists of the Palm Beaches, P.A.

🇺🇸

West Palm Beach, Florida, United States

East-West Medical Research Institute

🇺🇸

Honolulu, Hawaii, United States

Rehabilitation Institue of Chicago

🇺🇸

Chicago, Illinois, United States

Preventive Medicine

🇺🇸

Chicago, Illinois, United States

Clinical Investigation Specialists, Inc.

🇺🇸

Kenosha, Wisconsin, United States

Illinois Bone and Joint Institute, LLC

🇺🇸

Morton Grove, Illinois, United States

Ronald Keith Stegemoller, American Health Network

🇺🇸

Avon, Indiana, United States

The Arthritis Center

🇺🇸

Springfield, Illinois, United States

Floyd Memorial Hospital

🇺🇸

New Albany, Indiana, United States

Heartland Research Associates, LLC

🇺🇸

Wichita, Kansas, United States

Family Medicine East, Chartered/Radiology

🇺🇸

Wichita, Kansas, United States

Commonwealth Biomedical Research, LLC

🇺🇸

Madisonville, Kentucky, United States

Miray Medical Center

🇺🇸

Brockton, Massachusetts, United States

Planters Clinic

🇺🇸

Port Gibson, Mississippi, United States

Mercy Medical Group/Woodlake Research

🇺🇸

Clarkson Valley, Missouri, United States

Office of Danka Michaels, MD

🇺🇸

Las Vegas, Nevada, United States

Regional Clinical Research, Inc.

🇺🇸

Endwell, New York, United States

Optimed Research, LLC

🇺🇸

Columbus, Ohio, United States

NYU Hospital for Joint Diseases

🇺🇸

New York, New York, United States

PharmQuest

🇺🇸

Greensboro, North Carolina, United States

Research Institute of the Carolinas, PLLC

🇺🇸

Mooresville, North Carolina, United States

Advantage Diagnostics

🇺🇸

Beachwood, Ohio, United States

Piedmont Healthcare/Research

🇺🇸

Statesville, North Carolina, United States

Carolina Arthritis Associates, PA

🇺🇸

Wilmington, North Carolina, United States

Altoona Center for Clinical Research

🇺🇸

Duncansville, Pennsylvania, United States

Columbus Clinical Research, Inc.

🇺🇸

Columbus, Ohio, United States

Lake Health Lyndhurst Clinic

🇺🇸

Lyndhurst, Ohio, United States

East Penn Rheumatology Associates, PC

🇺🇸

Bethlehem, Pennsylvania, United States

Memorial Hospital of Rhode Island

🇺🇸

Pawtucket, Rhode Island, United States

Radiant Research, Inc.

🇺🇸

Greer, South Carolina, United States

BioImaging Technologies, Inc.

🇺🇸

Newtown, Pennsylvania, United States

Parkway Medical Group

🇺🇸

Fayetteville, Tennessee, United States

National Clinical Research, Incorporated

🇺🇸

Richmond, Virginia, United States

Investigaciones Reumatológicas y Osteológicas S.R.L.

🇦🇷

Buenos Aires, Argentina

Saint Dennis Medical Group S.A.

🇦🇷

Buenos Aires, Argentina

Ustredni vojenska nemocnice Praha

🇨🇿

Praha 6, Czech Republic

City Alexandrovskaya Hospital

🇷🇺

St. Petersburg, Russian Federation

Hospital Nuestra Señora de Valme

🇪🇸

Sevilla, Spain

Martin Bowen Hefley Orthopedics

🇺🇸

Little Rock, Arkansas, United States

Southwind Medical Specialists

🇺🇸

Memphis, Tennessee, United States

Rheumatology Associates

🇺🇸

Charleston, South Carolina, United States

Radiant Research

🇺🇸

West Palm Beach, Florida, United States

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