Clinical trial NCT00669409: A Phase 1/2A, Single Dose Study Of PF-04383119 In Japanese Patients With Moderate To Severe Pain From Osteoarthritis Of The Knee
Official title: A PHASE 1/2A, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE BLIND, DOSE-ESCALATION, MULTICENTER STUDY OF THE SAFETY, TOLERABILITY, EFFICACY AND PHARMACOKINETICS, OF A SINGLE INTRAVENOUS DOSE OF PF-04383119 IN JAPANESE PATIENTS WITH MODERATE TO SEVERE PAIN FROM OSTEOARTHRITIS OF THE KNEE
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Keywords: monoclonal antibody
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-04-30
Enrollment: 83
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and tolerability of single IV doses of PF-04383119 in Japanese patients with moderate to severe pain from OA of the knee (Part I). To evaluate the preliminary analgesic efficacy of PF-04383119 in Japanese patients with moderate to severe pain from OA of the knee in comparison with placebo (Part I and Part II).


Eligibility criteria: Inclusion Criteria:

* Japanese Male or female, Age 35-65 (Part 1), Age 35-75 (Part 2)
* Diagnosis of osteoarthritis (OA) of the knee based on American College of Rheumatology criteria
* Knee pain, and radiographic evidence of knee OA (Kellgren-Lawrence x-ray grade ≥2) obtained within 1 year of enrollment
* At least one of the following: age \>50, morning stiffness \<30 minutes in duration, crepitus, and OA of the knee must involve the index tibiofemoral joint and must have present for at least 6 months
* Patients who meet at least one of the following: unwilling to take non-opiate pain medications, or for whom non-opiate pain medications have failed, or are candidates for or seeking invasive interventions such as intraarticular injections, knee arthroplasty, or total knee surgery
* Pain levels as required by the protocol at Screening and Baseline

Exclusion Criteria:

* Diagnosis or history of RA, any inflammatory arthritis, gout, Paget's disease or any other disease that in the Investigator's opinion would interfere with the assessment of pain and other symptoms of OA
* Patients with regional pain syndromes suggestive of fibromyalgia or regional pain caused by lumbar or cervical compressions with radiculopathy or at risk of developing radiculopathy.
* Diagnosis or history of fibromyalgia
* Planned surgical procedure during the duration of the study

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Day 92 for tanezumab 10, 25, 50 mcg/kg group and matching placebo group (Part 1, 2); Day 1 up to Day 120 for tanezumab 100 mcg/kg group and matching placebo group (Part 1, 2), 200 mcg/kg group and matching placebo group (Part 1)
measure: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score at Baseline
timeFrame: Baseline (Part 1 and Part 2)
measure: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score at Day 1
timeFrame: Day 1 (Part 1 and 2)
measure: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score at Day 4/5
timeFrame: Day 4/5 (Part 1 and 2)
measure: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score at Week 1
timeFrame: Week 1 (Part 1 and Part 2)
measure: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score at Week 2
timeFrame: Week 2 (Part 1 and Part 2)
measure: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score at Week 3
timeFrame: Week 3 (Part 1 and 2)
measure: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score at Week 4
timeFrame: Week 4 (Part 1 and Part 2)
measure: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score at Week 13
timeFrame: Week 13 (Part 1 and Part 2)
measure: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score at Week 17
timeFrame: Week 17 (Part 1 and Part 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 1
timeFrame: Baseline, Week 1 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 2
timeFrame: Baseline, Week 2 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 3
timeFrame: Baseline, Week 3 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 4
timeFrame: Baseline, Week 4 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 5
timeFrame: Baseline, Week 5 (Part 1 and 2)
measure: Change From Baseline In Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 6
timeFrame: Baseline, Week 6 (Part 1 and 2)
measure: Change From Baseline In Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 7
timeFrame: Baseline, Week 7 (Part 1 and 2)
measure: Change From Baseline In Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 8
timeFrame: Baseline, Week 8 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 9
timeFrame: Baseline, Week 9 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 10
timeFrame: Baseline, Week 10 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 11
timeFrame: Baseline, Week 11 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 12
timeFrame: Baseline, Week 12 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Current Index Knee Pain at Week 13
timeFrame: Baseline, Week 13 (Part 1 and 2)
measure: Change From Baseline Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 1
timeFrame: Baseline, Week 1 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 2
timeFrame: Baseline, Week 2 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 3
timeFrame: Baseline, Week 3 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 4
timeFrame: Baseline, Week 4 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in The Past 24 Hours at Week 5
timeFrame: Baseline, Week 5 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 6
timeFrame: Baseline, Week 6 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 7
timeFrame: Baseline, Week 7 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 8
timeFrame: Baseline, Week 8 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 9
timeFrame: Baseline, Week 9 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 10
timeFrame: Baseline, Week 10 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 11
timeFrame: Baseline, Week 11 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 12
timeFrame: Baseline, Week 12 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain in the Past 24 Hours at Week 13
timeFrame: Baseline, Week 13 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 1
timeFrame: Baseline, Week 1 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 2
timeFrame: Baseline, Week 2 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 3
timeFrame: Baseline, Week 3 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 4
timeFrame: Baseline, Week 4 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 5
timeFrame: Baseline, Week 5 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 6
timeFrame: Baseline, Week 6 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 7
timeFrame: Baseline, Week 7 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 8
timeFrame: Baseline, Week 8 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 9
timeFrame: Baseline, Week 9 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 10
timeFrame: Baseline, Week 10 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 11
timeFrame: Baseline, Week 11 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 12
timeFrame: Baseline, Week 12 (Part 1 and 2)
measure: Change From Baseline in Visual Analogue Scale (VAS) Score For Index Knee Pain During Walking in the Past 24 Hours at Week 13
timeFrame: Baseline, Week 13 (Part 1 and 2)
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Version 3.1 (WOMAC 3.1) Subscales Scores at Week 1
timeFrame: Baseline, Week 1 (Part 1 and 2)
measure: Change From Baseline in WOMAC 3.1 Subscales Scores at Week 2
timeFrame: Baseline, Week 2 (Part 1 and 2)
measure: Change From Baseline in WOMAC 3.1 Subscales Scores at Week 4
timeFrame: Baseline, Week 4 (Part 1 and 2)
measure: Change From Baseline in WOMAC 3.1 Subscales Scores at Week 8
timeFrame: Baseline, Week 8 (Part 1 and 2)
measure: Change From Baseline in WOMAC 3.1 Subscales Scores at Week 13
timeFrame: Baseline, Week 13 (Part 1 and 2)
measure: Change From Baseline in WOMAC 3.1 Subscales Scores at Week 17
timeFrame: Baseline, Week 17 (Part 1 and 2)
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) - Part 1
timeFrame: Part 1: Pre-dose, Day 1 (10 minutes, 0.5, 1, 4, 12 hours post intravenous infusion), Day 2, 3, 4/5, 8, 15, 22, 29, 43, 57, 71, 92, 120 post-infusion
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) - Part 1
timeFrame: Part 1: Pre-dose, Day 1 (10 minutes, 0.5, 1, 4, 12 hours post intravenous infusion), Day 2, 3, 4/5, 8, 15, 22, 29, 43, 57, 71, 92, 120 post-infusion
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-infinity)] - Part 1
timeFrame: Part 1: Pre-dose, Day 1 (10 minutes, 0.5, 1, 4, 12 hours post intravenous infusion), Day 2, 3, 4/5, 8, 15, 22, 29, 43, 57, 71, 92, 120 post-infusion
measure: Area Under The Curve From Time Zero to Last Quantifiable Concentration (AUClast) - Part 1
timeFrame: Part 1: Pre-dose, Day 1 (10 minutes, 0.5, 1, 4, 12 hours post intravenous infusion), Day 2, 3, 4/5, 8, 15, 22, 29, 43, 57, 71, 92, 120 post-infusion
measure: Volume of Distribution (Vz) - Part 1
timeFrame: Part 1: Pre-dose, Day 1 (10 minutes, 0.5, 1, 4, 12 hours post intravenous infusion), Day 2, 3, 4/5, 8, 15, 22, 29, 43, 57, 71, 92, 120 post-infusion
measure: Volume of Distribution At Steady State (Vss) - Part 1
timeFrame: Part 1: Pre-dose, Day 1 (10 minutes, 0.5, 1, 4, 12 hours post intravenous infusion), Day 2, 3, 4/5, 8, 15, 22, 29, 43, 57, 71, 92, 120 post-infusion
measure: Systemic Clearance (CL) - Part 1
timeFrame: Part 1: Pre-dose, Day 1 (10 minutes, 0.5, 1, 4, 12 hours post intravenous infusion), Day 2, 3, 4/5, 8, 15, 22, 29, 43, 57, 71, 92, 120 post-infusion
measure: Mean Residence Time (MRT) - Part 1
timeFrame: Part 1: Pre-dose, Day 1 (10 minutes, 0.5, 1, 4, 12 hours post intravenous infusion), Day 2, 3, 4/5, 8, 15, 22, 29, 43, 57, 71, 92, 120 post-infusion
measure: Plasma Decay Half-Life (t1/2) - Part 1
timeFrame: Part 1: Pre-dose, Day 1 (10 minutes, 0.5, 1, 4, 12 hours post intravenous infusion), Day 2, 3, 4/5, 8, 15, 22, 29, 43, 57, 71, 92, 120 post-infusion
measure: Percentage of Participants With Positive Anti-tanezumab Antibody Test Results
timeFrame: Baseline up to Day 120
Other outcomes:
Locations:
city: Takasaki
country: Japan
facility: National Hospital Organization Takasaki General Medical Center
state: Gunma
city: Fujisawa-shi
country: Japan
facility: Fujisawa shounandai Hospital
state: Kanagawa-ken
city: Yokohama-shi
country: Japan
facility: Medical Corporation Yamamoto Kinenkai Yamamoto Kinen Hospital
state: Kanagawa-ken
city: Kawasaki
country: Japan
facility: Nippon Kokan Clinic
state: Kanagawa
city: Beppu-shi
country: Japan
facility: Nakamura Hospital
state: Oita
city: Fuchu City,
country: Japan
facility: Tokyo Metropolitan Fuchu Hospital
state: Tokyo
city: Minato-ku
country: Japan
facility: FuruKawabashi Hospital
state: Tokyo
city: Minato-ku
country: Japan
facility: Research Hospital, the Institute of Medical Science, the University of Tokyo
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Kitashinagawa Third Hospital
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Oosaki Hospital Tokyo Heart Center
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Kanto Medical Center Ntt Ec
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: International Medical Center of Japan Toyama Hospital
state: Tokyo
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Nagashima H, Suzuki M, Araki S, Yamabe T, Muto C; Tanezumab Investigators. Preliminary assessment of the safety and efficacy of tanezumab in Japanese patients with moderate to severe osteoarthritis of the knee: a randomized, double-blind, dose-escalation, placebo-controlled study. Osteoarthritis Cartilage. 2011 Dec;19(12):1405-12. doi: 10.1016/j.joca.2011.09.006. Epub 2011 Oct 5.