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

A Long-Term, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Radiographic Study To Investigate The Safety And Efficacy Of Orally Administered SD-6010 In Subjects With Symptomatic Osteoarthritis Of The Knee

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: SD-6010; Drug: SD-6010; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1457
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1034ACO
    • Saint Dennis Medical Group S.A.
  • Buenos Aires, Argentina, C1425AWC
    • IMAI Research
  • Buenos Aires, Argentina, C1405BCH
    • Instituto Médico Especializado (IME)
  • Buenos Aires, Argentina, C1013AAR
    • OMI - Organización Médica de Investigación
  • Buenos Aires, Argentina, C1114AAH
    • Investigaciones Reumatológicas y Osteológicas S.R.L.
• Australia
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Menzies Research Institute
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St Luc
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Gasthuisberg / Rheumatology
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5M 0H4
      • Rheumatology Research Associates Ltd.
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1A 5E8
      • Nexus Clinic Research
  • Ontario
    • Newmarket, Ontario, Canada, L3Y 3R7
      • The Arthritis Program Research Group Inc.
  • Quebec
    • Sainte-Foy, Quebec, Canada, G1W 4R4
      • Centre de Rhumatologie St-Louis
• Czech Republic
  • Brno, Czech Republic, 656 91
    • Fakultni nemocnice u sv. Anny v Brne
  • Brno - Zidenice, Czech Republic, 615 00
    • Revmacentrum MUDr. Mostera, s.r.o.
  • Ceske Budejovice, Czech Republic, 370 01
    • MEDIPONT Plus, s.r.o.
  • Ceske Budejovice, Czech Republic, 370 01
    • MEDIPONT, s.r.o.
  • Hostivice, Czech Republic, 253 01
    • ARTMEDI UPD s r.o.
  • Praha 1, Czech Republic, 11000
    • Nemocnice Na Frantisku s poliklinikou
  • Praha 11 - Chodov, Czech Republic, 148 00
    • DC Mediscan
  • Praha 11 - Chodov, Czech Republic, 148 00
    • MediCentrum Praha, a.s.
  • Praha 2, Czech Republic, 128 50
    • Revmatologicky Ustav
  • Praha 6, Czech Republic, 162 00
    • Centrum pro zdravotnicke zabezpeceni sportovni reprezentace
  • Praha 6, Czech Republic, 162 00
    • Ustredni vojenska nemocnice Praha
  • Praha 6, Czech Republic, 169 00
    • MSI - Muskuloskeletalni institut
  • Zlin, Czech Republic, 760 01
    • Nemocnice Atlas, a.s.
  • Zlin, Czech Republic, 760 01
    • PV-MEDICAL s.r.o.
• Germany
  • Bad Hersfeld, Germany, 36251
    • Praxis fuer Orthopaedie, Chirotherapie und Akupunktur
  • Berlin, Germany, 12247
    • Praxis fuer Orthopaedie
  • Berlin, Germany, 13125
    • Klinische Forschung Berlin-Buch
  • Deggingen, Germany, 73326
    • Praxis Dr. Thomas Jung
  • Schwerin, Germany, 19055
    • Klinische Forschung Schwerin
• Hungary
  • Budapest, Hungary, H-1036
    • Synexus Magyarorszag Kft.
  • Budapest, Hungary, 1126
    • Orszagos Gerincgyogyaszati Kozpont
  • Eger, Hungary, 3300
    • Heves Megyei Onkormanyzat Markhot Ferenc Korhaz
  • Gyula, Hungary, 5700
    • Bekes Megyei Kepviselo-testulet Pandy Kalman Korhaz, Reumatologia
  • Komarom, Hungary, 2900
    • Selye Janos Korhaz, Reumatologiai Szakrendelo
  • Szolnok, Hungary, H-5000
    • MAV Korhaz es Rendelointezet
  • Veszprem, Hungary, H-8200
    • Veszprém Megyei Önkormányzat Csolnoky Ferenc Kórház-Rendelöintézet
• Italy
  • Arenzano, Italy, 16011
    • Azienda Sanitaria Genovese, Ospedale La Colletta, Dipartimento Apparato Locomotore
  • Jesi (Ancona), Italy, 60035
    • Presidio Ospedaliero Augusto Murri, Reparto di Reumatologia
  • Milano, Italy, 20157
    • Ospedale Luigi Sacco, Azienda Ospedaliera Polo Universitario Unita' Operativa di Reumatologia
• Peru
  • Callao, Peru, Callao-02
    • Hospital Nacional "Alberto Sabogal Sologuren" - Essalud
  • Lima, Peru, L-11
    • Clinica San Felipe
  • Lima, Peru, L-11
    • Hospital Nacional "Edgardo Rebagliati Martins" - Essalud
  • Lima, Peru, L-27
    • Instituto Peruano del Hueso y la Articulación SAC.
  • Lima, Peru, L-29
    • Hospital Maria Auxiliadora
  • Lima, Peru, Lima-27
    • Centro Medico CORPAC
  • Lima
    • Santiago de Surco, Lima, Peru, Lima 33
      • Instituto de Ginecología y Reproducción & Cirugía Mínimamente Invasiva
    • Santiago de Surco, Lima, Peru, Lima 33
      • Centro Empresarial - Altavista Polo 4
• Poland
  • Cieszyn, Poland, 43-400
    • NSZOZ "MEDICUS II" S.C. Irena Klimczak, Malgorzata Klimczak, Jerzy Klimczak
  • Wroclaw, Poland, 50-088
    • "SYNEXUS SCM" Sp. z o.o.
  • Wroclaw, Poland, 50-556
    • Katedra i Klinika Ortopedii i Traumatologii Narzadu Ruchu
• Russian Federation
  • Moscow, Russian Federation, 115093
    • Russian State Medical University, Moscow Faculty, City Clinical Hospital #4
  • Moscow, Russian Federation, 115522
    • Institute of Rheumatology
  • St. Petersburg, Russian Federation, 193312
    • City Alexandrovskaya Hospital
  • St. Petersburg, Russian Federation, 194291
    • L.G. Sokolov Clinical Hospital #122 of Federal Medical-Biology Agency of Russia, Central Polyclinic
  • St. Petersburg, Russian Federation, 195427
    • Research Institute of Traumatology and Orthopedy Named After R. R. Vredena
• Slovakia
  • Bratislava, Slovakia, 826 06
    • V. Interna klinika FN a LF UK
  • Bratislava, Slovakia
    • Ivan Ujvari
  • Piestany, Slovakia, 921 12
    • Narodny ustav reumatickych chorob
• Spain
  • Guadalajara, Spain, 19002
    • Hospital General Universitario de Guadalajara
  • Sevilla, Spain, 41014
    • Hospital Nuestra Senora de Valme
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15705
      • Hospital Ntra. Sra. de La Esperanza
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Brookwood Internists, P.C.
    • Birmingham, Alabama, United States, 35242
      • Greystone Medical Center
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Pivotal Research Centers
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
    • Phoenix, Arizona, United States, 85027
      • Pivotal Research Centers
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Martin Bowen Hefley Orthopedics
    • Little Rock, Arkansas, United States, 72205
      • Teton Research, LLC
  • California
    • Carmichael, California, United States, 95608
      • Med Center
    • Costa Mesa, California, United States, 92627
      • College Hospital Costa Mesa
    • Costa Mesa, California, United States, 92627
      • NeuroNetwork Trials
    • Fair Oaks, California, United States, 95628
      • Med Investigations, Inc.
    • Roseville, California, United States, 95661
      • Sierra Clinical Research
    • Sacramento, California, United States, 95817
      • University of California Davis
    • Sacramento, California, United States, 95817
      • University of California Davis Health System
    • San Diego, California, United States, 92128
      • Scripps Clinic-Clinical Research
    • Santa Ana, California, United States, 92704
      • Plaza Medical Imaging
  • Colorado
    • Denver, Colorado, United States, 80209
      • Denver Internal Medicine Group
    • Denver, Colorado, United States, 80209
      • Mountain View Clinical Research, Inc.
    • Golden, Colorado, United States, 80401
      • New West Physicians Clinical Research
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Advanced Radiology Consultants
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
    • Stamford, Connecticut, United States, 06902
      • Advanced Radiology Consultants
    • Trumbull, Connecticut, United States, 06611
      • New England Research Associates, LLC
  • Florida
    • Gainesville, Florida, United States, 32607
      • Southeastern Arthritis Center
    • Gainesville, Florida, United States, 32607
      • Southeastern Integrated Medical, PL, d/b/a Florida Medical Research Institute
    • Gainesville, Florida, United States, 32607
      • Southeastern Imaging & Diagnostics
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clincal Research
    • Jacksonville, Florida, United States, 32216
      • Memorial Hospital Jacksonville
    • Plantation, Florida, United States, 33317
      • Gold Coast Research, LLC
    • Plantation, Florida, United States, 33317
      • Marin E. Hale, M.D., P.A.
    • Plantation, Florida, United States, 33324
      • Sabiha Khan, M.D.
    • West Palm Beach, Florida, United States, 33407
      • Radiant Research
    • West Palm Beach, Florida, United States, 33407
      • Kanner, Mendelson, Shteinman, LLC
    • West Palm Beach, Florida, United States, 33407
      • Rheumatology and Endocrinology Specialists of the Palm Beaches, P.A.
  • Georgia
    • Marietta, Georgia, United States, 30060
      • North Georgia Clinical Research
    • Woodstock, Georgia, United States, 30189
      • North Georgia Clinical Research
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Preventive Medicine
    • Chicago, Illinois, United States, 60611
      • Rehabilitation Institue of Chicago
    • Evanston, Illinois, United States, 60201
      • Northshore University Healthsystem
    • Glenview, Illinois, United States, 60025
      • Northshore University Healthsystem
    • Gurnee, Illinois, United States, 60031
      • Clinical Investigation Specialists, Inc.
    • Morton Grove, Illinois, United States, 60053
      • Illinois Bone and Joint Institute, LLC
    • Springfield, Illinois, United States, 62704
      • The Arthritis Center
    • Vernon Hills, Illinois, United States, 60061
      • Northshore University Healthsystem
  • Indiana
    • Avon, Indiana, United States, 46123
      • Ronald Keith Stegemoller, American Health Network
    • New Albany, Indiana, United States, 47150
      • Floyd Memorial Hospital
  • Kansas
    • Wichita, Kansas, United States, 67205
      • Heartland Research Associates, LLC
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
    • Wichita, Kansas, United States, 67207
      • Family Medicine East, Chartered/Radiology
  • Kentucky
    • Lexington, Kentucky, United States, 40517
      • Office of Manoj Kohli, M.D.
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
    • Madisonville, Kentucky, United States, 42431
      • Commonwealth Biomedical Research, LLC
  • Louisiana
    • Shreveport, Louisiana, United States, 71115
      • TFD Research, LLC
  • Maine
    • Portland, Maine, United States, 04102
      • Rheumatology Associates
  • Maryland
    • Rockville, Maryland, United States, 20850
      • The Center for Rheumatology and Bone Research
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Miray Medical Center
    • Fall River, Massachusetts, United States, 02720
      • Phase III Clinical Research
    • Fall River, Massachusetts, United States, 02721
      • Fall River Clinical Research
    • New Bedford, Massachusetts, United States, 02740
      • HCI Metromedic Walk-In
    • Wellesley Hills, Massachusetts, United States, 02481-2106
      • MedVadis Research Corporation
    • Worcester, Massachusetts, United States, 01605
      • Fallon Clinic, Inc. (Drug Shipment)
    • Worcester, Massachusetts, United States, 01605
      • Fallon Clinic, Inc.
  • Michigan
    • Cadillac, Michigan, United States, 49601
      • Cadillac Clinical Research, LLC, located at Great Lakes Family Care
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Arthritis and Osteoporosis Treatment and Research Center
    • Port Gibson, Mississippi, United States, 39150
      • Planters Clinic
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Medical Center, Inc.
  • Missouri
    • Clarkson Valley, Missouri, United States, 63011
      • Mercy Medical Group/Woodlake Research
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research, P.C.
    • Kansas City, Missouri, United States, 64114
      • Dynamic Clinical Research, Inc.
    • Kansas City, Missouri, United States, 64114
      • Joan Prouty Moore, MD
    • Kansas City, Missouri, United States, 64114
      • Orthopaedic and Occupational Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Office of Danka Michaels, MD
    • Las Vegas, Nevada, United States, 89106
      • Affiliated Clinical Research, Inc.
    • Las Vegas, Nevada, United States, 89109
      • Office of Michael Mall, M.D.
    • Las Vegas, Nevada, United States, 89117
      • Nevada Imaging Centers
    • Las Vegas, Nevada, United States, 89118
      • Nevada Imaging Centers
    • Las Vegas, Nevada, United States, 89144
      • Office of Stephen H. Miller, MD
  • New York
    • Endwell, New York, United States, 13760
      • Regional Clinical Research, Inc.
    • New York, New York, United States, 10003
      • NYU Hospital for Joint Diseases
    • Rochester, New York, United States, 14625
      • VirtualScopics, Inc.
    • Syracuse, New York, United States, 13210
      • Crouse Medical Practice, PLLC d/b/a Internist Associates of Central New York
  • North Carolina
    • Burlington, North Carolina, United States, 27215
      • Kernodle Clinic Inc.
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Greensboro, North Carolina, United States, 27407
      • Southeastern Radiology
    • Mooresville, North Carolina, United States, 28117
      • Research Institute of the Carolinas, PLLC
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury
    • Statesville, North Carolina, United States, 28625
      • Piedmont Healthcare/Research
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
    • Wilmington, North Carolina, United States, 28401
      • Carolina Arthritis Associates, PA
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Lillestol Research, LLC
    • Fargo, North Dakota, United States, 58103
      • Internal Medicine Associates
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Advantage Diagnostics
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc.
    • Columbus, Ohio, United States, 43235
      • Optimed Research, LLC
    • Columbus, Ohio, United States, 43213
      • Columbus Clinical Research, Inc.
    • Lyndhurst, Ohio, United States, 44124
      • Lake Health Lyndhurst Clinic
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • East Penn Rheumatology Associates, Pc
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
    • Newtown, Pennsylvania, United States, 18940
      • BioImaging Technologies, Inc.
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Memorial Hospital of Rhode Island
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Rheumatology Associates
    • Greer, South Carolina, United States, 29651
      • Radiant Research, Inc.
  • Tennessee
    • Fayetteville, Tennessee, United States, 37334
      • Parkway Medical Group
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
    • Knoxville, Tennessee, United States, 37920
      • D. Matthew Sellers MD PC
    • Memphis, Tennessee, United States, 38125
      • Southwind Medical Specialists
  • Texas
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research Center
    • Dallas, Texas, United States, 75231
      • Baylor Research Institute
    • San Antonio, Texas, United States, 78217
      • Radiant Research San Antonio Northeast
    • San Antonio, Texas, United States, 78217
      • South Texas Radiology Imaging Center
    • San Antonio, Texas, United States, 78218
      • Oakwell Clinical research, LLC
  • Utah
    • Midvale, Utah, United States, 84047
      • Pivotal Research Centers
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • National Clinical Research - Norfolk, Inc.
    • Richmond, Virginia, United States, 23294
      • National Clinical Research, Incorporated
    • Virginia Beach, Virginia, United States, 23454
      • Advanced Pain Management
  • Washington
    • Tacoma, Washington, United States, 98405
      • Tacoma Center for Arthritis Research, PS
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53142
      • Clinical Investigation Specialists, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 200 mg; High dose active comparator	Drug: SD-6010; 200 mg tablets once a day for 2 years; Drug: SD-6010; 50 mg tablets once a day for 2 years
ACTIVE_COMPARATOR: 50 mg; Low dose active comparator	Drug: SD-6010; 200 mg tablets once a day for 2 years; Drug: SD-6010; 50 mg tablets once a day for 2 years
PLACEBO_COMPARATOR: Placebo; Placebo comparator to be used for control purposes	Drug: Placebo; Placebo tablets once a day for 2 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Progression of Joint Space Narrowing	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.	Baseline up to Month 24
Rate of Progression of Joint Space Narrowing in Participants With Kellgren and Lawrence Grade Less Than or Equal to (<=) 2	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.	Baseline up to Month 24
Rate of Progression of Joint Space Narrowing in Participants With Kellgren and Lawrence Grade Equal to (=) 3	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.	Baseline up to Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index (WOMAC) Composite Index Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Pain Subscale Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Pain Stiffness Subscale Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Physical Function Subscale Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Patient Assessment of Arthritic Pain Visual Analog Scale (VAS) Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Patient Global Assessment of Arthritic Condition Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Physician's Global Assessment of Arthritic Condition Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Pain After a 50-foot Walk Using Pain Visual Analog Scale Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Total Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Constant Pain Subscale Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Intermittent Pain Subscale Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Osteoarthritis Research Society International (OARSI) Knee Function Survey Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score - Physical Function Short Form (KOOS-PS) Score at Month 3, 6, 12, 18 and 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.	Baseline, Month 3, 6, 12, 18, 24
Change From Baseline in Short Form-36 (SF-36) Physical Functioning Domain Score at Month 12 and 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.	Baseline, Month 12, 24
Change From Baseline in Short Form-36 Role - Physical Domain Score at Month 12 and 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.	Baseline, Month 12, 24
Change From Baseline in Short Form-36 Bodily Pain Domain Score at Month 12 and 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.	Baseline, Month 12, 24
Change From Baseline in Short Form-36 General Health Domain Score at Month 12 and 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.	Baseline, Month 12, 24
Change From Baseline in Short Form-36 Vitality Domain Score at Month 12 and 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.	Baseline, Month 12, 24
Change From Baseline in Short Form-36 Social Functioning Domain Score at Month 12 and 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.	Baseline, Month 12, 24
Change From Baseline in Short Form-36 Role-Emotional Domain Score at Month 12 and 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.	Baseline, Month 12, 24
Change From Baseline in Short Form-36 Mental Health Domain Score at Month 12 and 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.	Baseline, Month 12, 24
Change From Baseline in Short Form-36 Physical Health Component Score at Month 12 and 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.	Baseline, Month 12, 24
Change From Baseline in Short Form-36 Mental Health Component Score at Month 12 and 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.	Baseline, Month 12, 24
Number of Participants With EuroQoL-5D (EQ-5D) Mobility Domain Score	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.	Baseline, Month 12, 24
Number of Participants With EuroQoL-5D Self-Care Domain Score	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.	Baseline, Month 12, 24
Number of Participants With EuroQoL-5D Usual Activity Domain Score	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.	Baseline, Month 12, 24
Number of Participants With EuroQo-5D Pain and Discomfort Domain Score	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.	Baseline, Month 12, 24
Number of Participants With EuroQoL-5D Anxiety and Depression Domain Score	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.	Baseline, Month 12, 24
EuroQoL-5D Visual Analog Scale Score	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.	Baseline, Month 12, 24
Number of Participants With Increase in Total Analgesic Medication Use	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.	Month 12, 24
Number of Participants With Decrease in Total Analgesic Medication Use	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.	Month 12, 24
Patient Global Impression of Change Score	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.	Month 24
Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index	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.	Month 24
Number of Participants With Joint Space Narrowing Progression	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).	Month 24
Number of Participants Applicable for Virtual Joint Replacement	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).	Month 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 7-10 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. Adverse events included both serious and non-serious adverse events.	Baseline up to 7-10 days after last dose of study drug (Week 111)
Number of Participants With Electrocardiogram (ECG) Abnormalities	Atrial (enlargement, fibrillation, premature beat), axis deviation, atrioventricular (accelerated conduction, first/second degree block), left anterior and posterior hemiblock, left atrial hypertrophy, left and right (complete/incomplete bundle branch block, ventricular hypertrophy), QRS (high/low voltage, nonspecific, prolongation greater than [>]140 milliseconds [msec]), junctional/paced rhythm, intraventricular conduction delay (>120 msec), early repolarization, ventricular premature contraction and beat, prolonged QTC, sinus (arrhythmia, bradycardia/tachycardia), supraventricular extra systole and premature beat, short PR syndrome. Abnormal Q-wave (>=30 msec), P-wave left/right atrial abnormality, T-wave flattened/inverted abnormality, U-wave abnormality, ST-T indeterminate abnormality, ST-T nonspecific changes, ST-T changes compatible with ischemia and pericarditis. ECG findings were judged by investigators for qualitative evaluation of abnormalities.	Baseline, Month 3, 6, 12, 18, 24
Number of Participants With Laboratory Test Abnormalities	Criteria for laboratory abnormalities: Hemoglobin (Hgb), hematocrit (hct), red blood cell(RBC) count: less than(<)0.8*lower limit of normal(LLN), platelet: <0.5*LLN or greater than (>)1.75*upper limit of normal (ULN), white blood cell (WBC): <0.6*LLN or >1.5*ULN, lymphocyte, neutrophil:<0.8*LLN or >1.2*ULN, basophil, eosinophil, monocyte:>1.2*ULN; total bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, gammaglutamyl transferase, alkaline phosphatase:> 3.0*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN; blood urea nitrogen, creatinine:>1.3*ULN, uric acid >1.2*ULN; sodium <0.95*LLN or >1.05*ULN, potassium, chloride, calcium, magnesium, bicarbonate: <0.9*LLN or >1.1*ULN, phosphate <0.8*LLN or >1.2*ULN; glucose <0.6*LLN or >1.5*ULN, lipase >1.5*ULN; urine (specific gravity <1.003 or >1.030, pH <4.5 or >8, glucose, ketones, protein, blood/Hgb greater than or equal to [>=]1); pancreatic amylase >1.5*ULN.	Baseline up to Week 111
Change From Baseline in Systolic Blood Pressure (SBP) at Week 2, 4, 12, 24, 36, 48, 60, 72, 84 and 96	Blood pressure (BP) was measured by sphygmomanometer while participant was in supine position. Conditions were kept constant from visit to visit including observer, participant's same arm, cuff size, supine position, location, temperature, noise level. The same size BP cuff which was properly sized and calibrated, was used to measure BP each time.	Baseline, Week 2, 4, 12, 24, 36, 48, 60, 72, 84, 96
Change From Baseline in Diastolic Blood Pressure (DBP) at Week 2, 4, 12, 24, 36, 48, 60, 72, 84 and 96	BP was measured by sphygmomanometer while participant was in supine position. Conditions were kept constant from visit to visit including observer, participant's same arm, cuff size, supine position, location, temperature, noise level. The same size BP cuff which was properly sized and calibrated, was used to measure BP each time.	Baseline, Week 2, 4, 12, 24, 36, 48, 60, 72, 84, 96
Change From Baseline in Heart Rate at Week 2, 4, 12, 24, 36, 48, 60, 72, 84 and 96		Baseline, Week 2, 4, 12, 24, 36, 48, 60, 72, 84, 96

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Hellio le Graverand MP, Clemmer RS, Redifer P, Brunell RM, Hayes CW, Brandt KD, Abramson SB, Manning PT, Miller CG, Vignon E. A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee. Ann Rheum Dis. 2013 Feb;72(2):187-95. doi: 10.1136/annrheumdis-2012-202239. Epub 2012 Nov 10.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (ACTUAL): October 1, 2011
• Study Completion (ACTUAL): November 1, 2011

Study Registration Dates

• First Submitted: November 29, 2007
• First Submitted That Met QC Criteria: November 29, 2007
• First Posted (ESTIMATE): November 30, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): December 30, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: knee Osteoarthritis Disease Modifying Osteoarthritis Drug
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: A6171016; 2007-001457-26 (EUDRACT_NUMBER); ITIC (OTHER: Alias Study Number)