A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, CONTROLLED STUDY OF THE LONG-TERM ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB ALONE OR IN COMBINATION WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) VERSUS NSAIDS ALONE 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
- 2,720
- 试验地点
- 323
- 主要终点
- Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16
研究概览
简要总结
The purpose of this study is to investigate the long-term analgesic efficacy and safety of tanezumab for patients with osteoarthritis (OA) of the knee or hip currently experiencing partial benefit from, and are tolerating, non-steroidal anti-inflammatory drug (NSAID) therapy.
详细描述
This study was terminated on 28 October 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 99 Years（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 NSAID therapy of either naproxen 500-1000 mg/day or celecoxib 200 mg/day (either 100 mg BID or 200 mg QD) and be tolerating their NSAID regimen.
- •Pain level and function levels as required by the protocol at Screening and Baseline.
- •Willing to discontinue all non-study pain medications for osteoarthritis except rescue medication (acetaminophen) and not use prohibited pain medications throughout the duration of 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
- •Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to sever pain that may confound assessments or self-evaluation of the pain associated with OA.
- •Signs and symptoms of clinically significant cardiac disease with 6 months prior to screening.
- •Diagnosis of 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 1.7 mg/dL (men) or 1.5 mg/dL (women).
- •Patients on warfarin or other coumadin anticoagulant therapy and/or lithium therapy within 30 days prior to screening.
- •Known hypersensitivity to NSAIDs or cyclooxygenase inhibitors.
研究组 & 干预措施
IV Placebo + NSAID
Oral NSAID
干预措施: NSAID (Drug)
Tanezumab 5 mg
IV tanezumab 5 mg every 8 weeks (through Week 48)
干预措施: tanezumab (Biological)
Tanezumab 10 mg
IV tanezumab 10 mg every 8 weeks (through Week 48)
干预措施: tanezumab (Biological)
Tanezumab 5 mg + NSAID
IV doses of tanezumab 5 mg every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
干预措施: tanezumab (Biological)
Tanezumab 5 mg + NSAID
IV doses of tanezumab 5 mg every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
干预措施: NSAID (Drug)
Tanezumab 10 mg + NSAID
IV doses of tanezumab 10 mg every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
干预措施: tanezumab (Biological)
Tanezumab 10 mg + NSAID
IV doses of tanezumab 10 mg every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
干预措施: NSAID (Drug)
结局指标
主要结局
Change From Baseline in the 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 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). The WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Total score range for WOMAC pain subscale score was 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain.
Change From Baseline in the 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 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip).The WOMAC physical function subscale was comprised of 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis of index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated worse physical function. Total score range for WOMAC physical function subscale score was 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated worse physical function. Physical function refers to participant's ability to move around and perform usual activities of daily living.
Change From Baseline in the Patient Global Assessment (PGA) of Osteoarthritis at Week 16
时间窗: Baseline, Week 16
Patient global assessment of osteoarthritis was assessed by asking a question from participants: "Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today?" Participants responded by using a 5-point likert scale ranging from 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 scores indicating worse condition.
次要结局
- 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 Observation Carried Forward (BOCF)(Baseline, Weeks 2, 4, 8, 12, and 24)
- Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF)(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56)
- Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response: Baseline Observation Carried Forward (BOCF)(Weeks 2, 4, 8, 12, 16, and 24)
- Percentage of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score From Baseline at Weeks 2, 4, 8, 12, 16, and 24: BOCF(Baseline, Weeks 2, 4, 8, 12, 16, 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 Observation Carried Forward (BOCF)(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, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF)(Baseline, Weeks 2, 4, 8, 12, 24, 32, 40, 48, and 56)
- Change From Baseline in the Patient Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 24: Baseline Observation Carried Forward (BOCF)(Baseline, Weeks 2, 4, 8, 12, and 24)
- Change From Baseline in the Patient Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF)(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56)
- Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response: Last Observation Carried Forward (LOCF)(Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56)
- Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score: Baseline Observation Carried Forward (BOCF)(Baseline, Week 16)
- Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score: Last Observation Carried Forward (LOCF)(Baseline, Week 16)
- Percentage of Participants With at Least 30%, 50%, 70% and 90% Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score: Last Observation Carried Forward (LOCF)(Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56)
- Percentage of Participants With Improvement of At Least 2 Points in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12, 16, and 24: Baseline Observation Carried Forward (BOCF)(Weeks 2, 4, 8, 12, 16, and 24)
- Percentage of Participants With Improvement of Atleast 2 Points in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56: Last Observation Carried Forward (LOCF)(Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56)
- 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 Observation Carried Forward (BOCF)(Baseline, Weeks 2, 4, 8, 12, 16, and 24)
- Number of Participants Who Had Discontinued Study Due to Lack of Efficacy(Baseline up to Week 56)
- Time to Discontinuation Due to Lack of Efficacy(Baseline up to Week 56)
- Change From Baseline in Percent Work Time Missed Due to Osteoarthritis at Week 24 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): Baseline Observation Carried Forward (BOCF)(Baseline, Week 24)
- Change From Baseline in the Percent Activity Impairment Due to Osteoarthritis at Week 24 Assessed Using Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP): Baseline Observation Carried Forward (BOCF)(Baseline, Week 24)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF)(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24: Baseline Observation Carried Forward (BOCF)(Baseline, 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, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF)(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56)
- 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 Observation Carried Forward (BOCF)(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, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF)(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56)
- Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Week 12 and 24: Baseline Observation Carried Forward (BOCF)(Baseline, Weeks 12 and 24)
- Change From Baseline in Percent Work Time Missed Due to Osteoarthritis at Week 24 and 56 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): Last Observation Carried Forward (LOCF)(Baseline, Week 24 and 56)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Down Stairs at Weeks 2, 4, 8, 12, 16 and 24: Baseline Observation Carried Forward (BOCF)(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 Down Stairs at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF)(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56)
- Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Weeks 12, 24, 40 and 56: Last Observation Carried Forward (LOCF)(Baseline, Weeks 12, 24, 40, and 56)
- Percentage of Participants Who Used Rescue Medication: Observed Data(Weeks 1-2, 3-4, 5-8, 9-12, 13-16, 17-24, 25-32, 33-40, 41-48 and 49-56)
- Change From Baseline in Percent Impairment While Working Due to Osteoarthritis at Week 24 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): Baseline Observation Carried Forward (BOCF)(Baseline, Week 24)
- Percentage of Participants Who Used Rescue Medication: Last Observation Carried Forward (LOCF)(Weeks 1-2, 3-4, 5-8, 9-12, 13-16, 17-24, 25-32, 33-40, 41-48 and 49-56)
- Change From Baseline in Minimum Joint Space Width of the Index Hip at Week 56(Baseline, Week 56)
- Change From Baseline in Percent Impairment While Working Due to Osteoarthritis at Week 24 and 56 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): Last Observation Carried Forward (LOCF)(Baseline, Weeks 24 and 56)
- Change From Baseline in the Percent Overall Work Impairment Due to Osteoarthritis at Week 24 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): BOCF(Baseline, Week 24)
- Change From Baseline in the Percent Activity Impairment Due to Osteoarthritis at Week 24 and 56 Assessed Using Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP): Last Observation Carried Forward (LOCF)(Baseline, Weeks 24, and 56)
- Amount of Rescue Medication Used(Weeks 1-2, 3-4, 5-8, 9-12, 13-16, 17-24, 25-32, 33-40, 41-48, and 49-56)
- Change From Baseline in Medial Minimum Joint Space Width of the Index Knee at Week 56(Baseline, Week 56)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to Week 64)
- Change From Baseline in the Percent Overall Work Impairment Due to Osteoarthritis at Week 24 and 56 Assessed Using Work Productivity and Activity Impairment Questionnaire- Specific Health Problem (WPAI-SHP): LOCF(Baseline, Weeks 24 and 56)
- Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Observed Data(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, and 56)
- Number of Participants With Intravenous (IV) Doses of Study Medication(Baseline up to Week 48)
- Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Last Observation Carried Forward (LOCF)(Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56)
- Plasma Trough (Pre-dose) Concentration of Tanezumab(Predose on Day 1, Weeks 16, 24, 40, and 56)