A PHASE 3, RANDOMIZED, DOUBLE BLIND, CONTROLLED, MULTI CENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB ADDED ON TO DICLOFENAC SR IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE OR HIP
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 607
- 试验地点
- 73
- 主要终点
- Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis Score at Week 16
研究概览
简要总结
The purpose of this study is to investigate the analgesic efficacy and safety of tanezumab added on to diclofenac SR in patients with osteoarthritis of the knee or hip currently experiencing partial benefit from, and are tolerating, diclofenac 150 mg/day therapy.
详细描述
This study was terminated on 16 Nov 2010 following a US FDA clinical hold for tanezumab osteoarthritis clinical studies which halted dosing and enrollment of patients on 23 June 2010 for potential safety issues.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Osteoarthritis of the knee or hip according to ACR criteria with Kellgren-Lawrence X-ray grade equal to, or greater than,
- •Patients must be experiencing some benefit from their current stable dose regimen of oral diclofenac 150 mg/day and be tolerating their diclofenac regimen.
- •Pain and function levels as required by the protocol at Screening and Baseline.
- •Willing to discontinue all non-study pain medications throughout the study except as permitted per protocol.
- •Willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests and other study procedures.
排除标准
- •Pregnant women.
- •BMI greater than
- •History of other disease that may involve index knee or hip including inflammatory joint diseases, chrystalline disease (gout or pseudogout), endocrinopathies, metabolic joint diseases, lupus erythematosus, rheumatoid arthritis (RA), joint infections, neuropathic disorders, avascular necrosis, Paget's disease or tumors.
- •Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to severe pain that may confound assessments or self-evaluation of the pain associated with OA.
- •Signs and symptoms of clinically significant cardiac disease within 6 months prior to screening.
- •Diagnosis or TIA within 6 months prior to screening or diagnosis of stroke with residual deficits that would preclude completion of required study activities.
- •History, diagnosis , signs or symptoms of clinically significant neurological and/or psychiatric disease/disorder.
- •At Screening: uncontrolled hypertension, hemoglobin A1c greater than or equal to 10%, ALT or AST greater than or equal to 3X upper limit of normal, creatinine exceeding 150 micro-mol/L in men or 133 micro-mol/L in women.
- •Patients on warfarin or other coumadin anticoagulant therapy and/or lithium therapy within 30 days prior to Screening.
- •Known hypersensitivity to NSAIDs (eg, diclofenac), cyclooxygenase inhibitors or paracetamol (acetaminophen).
研究组 & 干预措施
Tanezumab 10 mg + diclofenac
IV tanezumab 10 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
干预措施: tanezumab (Biological)
Tanezumab 10 mg + diclofenac
IV tanezumab 10 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
干预措施: diclofenac (Drug)
Tanezumab 5 mg + diclofenac
IV tanezumab 5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
干预措施: tanezumab (Biological)
Tanezumab 5 mg + diclofenac
IV tanezumab 5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
干预措施: diclofenac (Drug)
Tanezumab 2.5 mg + diclofenac
IV tanezumab 2.5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
干预措施: tanezumab (Biological)
Tanezumab 2.5 mg + diclofenac
IV tanezumab 2.5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
干预措施: diclofenac (Drug)
IV placebo + diclofenac
IV placebo to match tanezumab every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
干预措施: diclofenac (Drug)
IV placebo + diclofenac
IV placebo to match tanezumab every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)
干预措施: IV placebo (Other)
结局指标
主要结局
Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis Score at Week 16
时间窗: Baseline, Week 16
Participants answered: "Considering all the ways your osteoarthritis in your index joint (knee/hip) affects you, how are you doing today?" Participants responded by using a 5-point Likert scale, where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher score indicated worst condition.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 16
时间窗: Baseline, Week 16
WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. WOMAC physical function is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee or hip during past 48 hours. It is calculated as mean of the scores from 17 individual questions, each scored on a NRS of 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. Physical function refers to participant's ability to move around and perform usual activities of daily living.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16
时间窗: Baseline, Week 16
WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis (OA). WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or hip during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain.
次要结局
- Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response; LOCF(Weeks 2, 4, 8, 12, 16, and 24)
- Percentage of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16 and 24(Baseline, Week 16 and 24)
- Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Weeks 2, 4, 8, 12 and 24(Baseline, Weeks 2, 4, 8, 12, and 24)
- Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Weeks 2, 4, 8, 12, and 24(Baseline, Weeks 2, 4, 8, 12, and 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 2, 4, 8, 12, 16, and 24(Baseline, Weeks 2, 4, 8, 12, 16, and 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 2, 4, 8, 12, 16, and 24(Baseline, Week 2, 4, 8, 12, 16, 24)
- Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis Score at Weeks 2, 4, 8, 12, and 24(Baseline, Weeks 2, 4, 8, 12, and 24)
- Percentage of Participants With Improvement of at Least 2 Points in Patient Global Assessment (PGA) of Osteoarthritis; LOCF(Weeks 2, 4, 8, 12, 16, and 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16, and 24(Baseline, Weeks 2, 4, 8, 12, 16, and 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Downstairs at Weeks 2, 4, 8, 12, 16, and 24(Baseline, Weeks 2, 4, 8, 12, 16, and 24)
- Number of Participants With Change From Baseline in European Quality of Life - 5 Dimension (EQ-5D) Individual Health State Profile at Week 24(Baseline, Week 24)
- Time to Discontinuation (TTD) Due to Lack of Efficacy(Baseline up to Week 16 and 24)
- Percentage of Participants With At Least 30%, 50%, 70% and 90% Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score; LOCF(Baseline, Weeks 2, 4, 8, 12, 16, and 24)
- Percentage of Participants With Improvement of at Least 2 Points in Patient Global Assessment (PGA) of Osteoarthritis; Baseline Observation Carried Forward (BOCF)(Weeks 2, 4, 8, 12, 16, and 24)
- Number of Participants Who Discontinued Due to Lack of Efficacy(Baseline up to end of study (Week 32))
- Change From Baseline in Average Pain Score in the Index Knee or Hip at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24(Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24)
- Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 12 and 24(Baseline, Week 12, and 24)
- Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 12 and 24(Baseline, Week 12 and 24)
- Change From Baseline in European Quality of Life - 5 Dimension (EQ-5D) Index Score at Week 24(Baseline, Week 24)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to 112 days after last intravenous dose (up to Week 32))