Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Other |
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 are events between first dose of study drug and up to 112 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
Baseline up to 112 days after last dose of study treatment |
|
| Other |
Number of Participants With Abnormal Laboratory Findings |
Laboratory examination included blood chemistry, hematology and urinalysis. Reported results include abnormal laboratory findings without regard to baseline abnormality. |
Day 1 up to Week 24 |
|
| Other |
Number of Participants With Abnormal Electrocardiogram (ECG) Findings |
Following parameters were analyzed for ECG abnormality: PR interval, QRS interval, QT interval, QT interval corrected using the Fridericia's formula (QTcF), QT interval corrected using the Bazett's formula (QTcB), RR interval and heart rate (HR). Number of participants with clinically significant abnormal ECG findings reported as adverse events were presented. |
Baseline up to Week 24 |
|
| Other |
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, and 24 |
The NIS constitutes the sum of 37 standard items of neuromuscular examination used to assess the muscle strength, reflexes and sensation. Each item is scored separately for left and right sides. Components of muscle weakness (24 items) are scored on a scale from 0 (normal) to 4 (paralysis), with higher score = more weakness; components of reflexes and sensation (13 items) scored on a scale with 0 = normal, 1 = decreased or 2 = absent. Total NIS score range 0-244 with higher score = more impairment. |
Baseline, Weeks 2, 4, 8, 12, 16, and 24 |
|
| Other |
Number of Participants With Anti-drug Antibodies (ADA) |
Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative enzyme-linked immunosorbent assay (ELISA). Same participant may have positive ADA result at more than 1 time point. |
Baseline, Weeks 8, 16, 24 or Early Termination |
|
| Other |
Number of Participants With Abnormal Physical Examination Findings |
Physical examination included examination of following sites in addition to general examination: abdomen, ears, extremities, eyes, head, heart, musculoskeletal, neck, nose, skin, throat, lungs and thyroid. |
Baseline up to Week 24 |
|
| Other |
Number of Participants With Clinically Significant Abnormality in Vital Signs |
Following parameters were analyzed for examination of vital signs: body temperature, blood pressure, pulse rate and respiratory rate. Number of participants with clinically significant abnormality in vital signs reported as adverse events were presented. |
Baseline to Week 24 |
|
| Other |
Number of Participants With Injection and Infusion Site Reactions |
The injection and infusion site reactions were assessed based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after administration of subcutaneous injection or intravenous infusion. |
Baseline, Weeks 1, 2, 4, 8, 12, 16, and 24 |
|
| Other |
Plasma Tanezumab Concentration |
|
Baseline (pre-dose), Weeks 1, 2, 4, 8 (pre-dose), 12, 16, 24 or End of treatment |
|
| Other |
Total and Free Nerve Growth Factor (NGF) Concentration |
Serum samples were analyzed for determining total and free (unbound) NGF concentration. Total NGF was analyzed using a validated, sensitive and specific immunoaffinity enrichment liquid chromatography tandem mass spectrometric (IA/LC/MS/MS) method and free (unbound) NGF was analyzed using a validated, sensitive, and specific electrochemiluminescence (ECL) ligand binding assay. |
Baseline (pre-dose), Weeks 1, 2, 4, 8 (pre-dose), 12, 16, and 24 or End of treatment |
|
| Other |
Number of Participants With Intravenous or Subcutaneous Doses of Study Medication |
Number of participants were reported based on the maximum number of intravenous or subcutaneous doses of either tanezumab or placebo received. |
Baseline up to Week 8 |
|
| Primary |
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16 |
The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. |
Baseline, Week 16 |
|
| Primary |
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 16 |
The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in the index joint in the past 48 hours. It is calculated as the mean of the scores from the 17 individual questions scored on a NRS of 0 to 10, where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 to 10, where higher scores indicate worse function. |
Baseline, Week 16 |
|
| Primary |
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis Score at Week 16 |
Participants answered the question: "Considering all the ways your osteoarthritis in your knee affects you, how are you doing today?" Participants responded by using a 5-point 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 severe condition. |
Baseline, Week 16 |
|
| Secondary |
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 1, 2, 4, 8, and 12 |
The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. |
Baseline, Weeks 1, 2, 4, 8, and 12 |
|
| Secondary |
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 1, 2, 4, 8, and 12 |
The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in the index joint in the past 48 hours. It is calculated as the mean of the scores from the 17 individual questions scored on a NRS of 0 to 10, where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 to 10, where higher scores indicate worse function. |
Baseline, Weeks 1, 2, 4, 8, and 12 |
|
| Secondary |
Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Weeks 1, 2, 4, 8, and 12 |
Participants answered the question: "Considering all the ways your osteoarthritis in your knee affects you, how are you doing today?" Participants responded by using a 5-point 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 severe condition. |
Baseline, Weeks 1, 2, 4, 8, and 12 |
|
| Secondary |
Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response |
The OMERACT-OARSI responder index is based on 3 parameters. OMERACT-OARSI response: greater than or equal to (>=) 50 percent (%) improvement from baseline and absolute change from baseline of >=2 units at week of interest in WOMAC pain or physical function subscale, or at least 2 of the following 3 being true: >=20% improvement from baseline and absolute change from baseline of >=1 unit at week of interest in 1) WOMAC pain subscale, 2) WOMAC physical function subscale, 3) PGA of osteoarthritis (score range: 1-5, higher score=more affected). WOMAC pain, physical function subscales assess amount of pain/difficulty experienced (score range: 0-10, higher score=higher pain/difficulty). |
Weeks 1, 2, 4, 8, 12, and 16 |
|
| Secondary |
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 |
The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. |
Weeks 1, 2, 4, 8, 12, and 16 |
|
| Secondary |
Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score at Weeks 1, 2, 4, 8, 12, and 16 |
The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a NRS of 0 to 10, where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. Participants with specified reduction (as percent) from baseline at Week 16 are reported. |
Weeks 1, 2, 4, 8, 12, 16 |
|
| Secondary |
Number of Participants With Improvement of at Least 2 Points in Patient's Global Assessment (PGA) of Osteoarthritis |
Participants answered the question: "Considering all the ways your osteoarthritis in your knee affects you, how are you doing today?" Participants responded by using a 5-point 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 severe condition. Improvement signifies a decrease of at least 2 points on the 5-point scale relative to baseline value. |
Weeks 1, 2, 4, 8, 12, and 16 |
|
| Secondary |
Change From Baseline in Average Pain Score in the Index Knee at Weeks 1, 2, 4, 8, 12 and 16 |
Participants assessed average osteoarthritis pain in their knee in the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst pain). Higher score indicated greater pain. Baseline score was calculated as the mean of the scores over the 3 days in the initial pain assessment period and a weekly mean was calculated using the daily pain scores within each study week. |
Baseline, Weeks 1, 2, 4, 8, 12, and 16 |
|
| Secondary |
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 1, 2, 4, 8, 12, and 16 |
The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced in the index joint in the past 48 hours. It is calculated as the mean of the scores from the 2 individual questions scored on NRS of 0 to 10, with higher scores indicating more stiffness. Total score range for WOMAC stiffness subscale score is 0 to 10, where higher scores indicate more stiffness. Stiffness is defined as a sensation of decreased ease in movement of the knee. |
Baseline, Weeks 1, 2, 4, 8, 12, and 16 |
|
| Secondary |
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 1, 2, 4, 8, 12, and 16 |
WOMAC: self-administered, disease-specific 24-item questionnaire, which assesses clinically important, participant-relevant symptoms for pain (5 items), stiffness (2 items) and physical function (17 items) in participants with osteoarthritis of knee. WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores. WOMAC pain, physical function and stiffness subscale and average score ranges from 0 to 10, where higher score indicates worse response. |
Baseline, Weeks 1, 2, 4, 8, 12, and 16 |
|
| Secondary |
Change From Baseline For Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 1, 2, 4, 8, 12, and 16 |
Participants answered: "How much pain have you had when walking on a flat surface?" Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain. Higher score indicated greater pain. |
Baseline, Weeks 1, 2, 4, 8, 12, and 16 |
|
| Secondary |
Change From Baseline For Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Down Stairs at Weeks 1, 2, 4, 8, 12, and 16 |
Participants answered: "How much pain have you had when going up or down stairs?" Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain. Higher score indicated greater pain. |
Baseline, Weeks 1, 2, 4, 8, 12, and 16 |
|
| Secondary |
Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 16 |
SF-36v2 is a standardized self-administered survey evaluating 8 aspects/domains of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The total score for each domain is scaled 0-100 (100 = highest level of functioning). |
Baseline, Week 16 |
|
| Secondary |
Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 16 |
SF-36v2: standardized self-administered survey evaluating 8 aspects of functional health and wellbeing (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health). Total score for each aspect were scaled 0-100 (100=highest level of functioning). For obtaining physical and mental component scores, z-score for each scale=(observed score - mean score for general 1990 United States [US] population)/corresponding standard deviation. The 2 component scores were obtained by multiplying each aspect z-score by physical or mental factor score coefficient (1990 general US population) and summing the eight products. Component scores indicated how many standard deviations higher (in case of positive z-score [better functioning])/lower (in case of negative z-score [worse functioning]) participant's value was relative to the mean of the reference population. |
Baseline, Week 16 |
|
| Secondary |
Time to Discontinuation Due to Lack of Efficacy |
Median time to discontinuation due to lack of efficacy for participants who discontinued due to lack of efficacy was reported. |
Baseline up to Week 24 |
|
| Secondary |
Percentage of Participants Who Used Rescue Medication |
In case of inadequate pain relief for osteoarthritis, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Incidence of rescue medication use is calculated as any use of rescue medication during the study week in question. |
Weeks 1, 2, 4, 8, 12, and 16 |
|
| Secondary |
Duration of Rescue Medication Use |
In case of inadequate pain relief for osteoarthritis, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Duration of rescue medication use is calculated as the number of study days per week when any rescue medication was taken. |
Weeks 1, 2, 4, 8, 12, and 16 |
|
| Secondary |
Amount of Rescue Medication Taken |
In case of inadequate pain relief for osteoarthritis, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. The amount of rescue medication taken is the total dose (in mg) of acetaminophen rescue medication over the study week in question. |
Weeks 1, 2, 4, 8, 12, and 16 |
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