Tanezumab in Osteoarthritis of the Hip or Knee (2)

WOMAC: self-administered, disease-specific 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 is 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 the mean of 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.

WOMAC: self-administered, disease-specific 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 is 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 the mean of 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.

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis in index joint (knee or hip). Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in 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 maximum difficulty. Total score range for WOMAC physical function subscale score was 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated worse physical function.

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis in index joint (knee or hip). Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in 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 maximum difficulty. Total score range for WOMAC physical function subscale score was 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated worse physical function.

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 on a scale ranging from 1=very good (no symptom and 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 and inability to carry out all normal activities). Higher scores indicated worse condition.

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 on a scale ranging from 1=very good (no symptom and 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 and inability to carry out all normal activities). Higher scores indicated worse condition.

Participants were considered as OMERACT-OARSI responder: if the improvement from baseline to week of interest was greater than or equal to (>=) 50 percent and >=2 units in WOMAC pain subscale or WOMAC physical function subscale score; if improvement from baseline to week of interest was >=20 percent and >=1 unit in at least 2 of the following: 1) WOMAC pain subscale score, 2) WOMAC physical function subscale score, 3) PGA of osteoarthritis. WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [worst possible pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [minimum difficulty] to 10 [maximum difficulty], higher score = worse physical function) and PGA of osteoarthritis (score: 1 [very good] to 5 [very poor], higher score = worse condition). Percentage of participants who were considered as OMERACT-OARSI responder were reported in this outcome measure.

Participants were considered as OMERACT-OARSI responder: if the improvement from baseline to week of interest was >=50 percent and >=2 units in WOMAC pain subscale or WOMAC physical function subscale score; if improvement from baseline to week of interest was >=20 percent and >=1 unit in at least 2 of the following: 1) WOMAC pain subscale score, 2) WOMAC physical function subscale score, 3) PGA of osteoarthritis. WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [worst possible pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [minimum difficulty] to 10 [maximum difficulty], higher score = worse physical function) and PGA of osteoarthritis (score: 1 [very good] to 5 [very poor], higher score = worse condition). Percentage of participants who were considered as OMERACT-OARSI responder were reported in this outcome measure.

WOMAC: self-administered, disease-specific 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 is 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 the mean of 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. Percentage of participants with at least 30 percent and 50 percent reduction in WOMAC pain subscale at specified weeks were reported in this outcome measure.

WOMAC: self-administered, disease-specific 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 is 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 the mean of 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. Percentage of participants with at least 30 percent and 50 percent reduction in WOMAC pain subscale at specified weeks were reported in this outcome measure.

PGA 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 on a scale ranging from 1=very good (no symptom and 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 and inability to carry out all normal activities). Higher scores indicated worse condition. Improvement signifies a decrease of at least 2 points on the 5-point scale relative to baseline value. Percentage of participants with improvement of at least 2 points in PGA of osteoarthritis were reported.

PGA 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 on a scale ranging from 1=very good (no symptom and 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 and inability to carry out all normal activities). Higher scores indicated worse condition. Improvement signifies a decrease of at least 2 points on the 5-point scale relative to baseline value. Percentage of participants with improvement of at least 2 points in PGA of osteoarthritis were reported.

WOMAC: self-administered, disease-specific 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 is 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 the mean of scores from 5 individual questions scored on a 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. Percentage of participants with cumulative reduction (as percent) (greater than 0 percent [%]; >= 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 % and 90%; = 100 %) in WOMAC pain subscale from Baseline up to Week 16 were reported.

WOMAC: self-administered, disease-specific 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 is 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 the mean of scores from 5 individual questions scored on a 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. Percentage of participants with cumulative reduction (as percent) (greater than 0%; >= 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 % and 90%; = 100 %) in WOMAC pain subscale from Baseline up to Week 16 were reported.

Participants assessed their average daily pain score in the index hip/knee using a scale ranging from 0 (no pain) to 10 (worst possible pain). Higher scores indicated higher pain. A weekly mean was calculated using the daily index hip/knee pain scores within each specified study week. Change from baseline was calculated using the difference between each post-baseline weekly mean and the baseline mean score.

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip).The WOMAC stiffness subscale was a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in the index joint (knee or hip) during the past 48 hours. It was calculated as mean of the scores from 2 individual questions scored on NRS of 0 (no stiffness) to 10 (worst stiffness), where higher scores indicated higher stiffness. Total score range for WOMAC stiffness subscale score was 0 (no stiffness) to 10 (worst stiffness), where higher scores indicated higher stiffness.

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis of index joint (knee or hip). WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [worst possible pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [minimum difficulty] to 10 [maximum difficulty], higher score = worse physical function) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 [no stiffness] to 10 [worst stiffness], higher score = higher stiffness). WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 (no difficulty) to 10 (maximum difficulty), where higher scores indicated worse response.

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis in index joint (knee or hip). Participants answered a question: "How much pain have you had when walking on a flat surface?". Participants responded about the amount of pain they experienced when walking on a flat surface by using a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain.

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis in index joint (knee or hip). Participants answered a question: "How much pain have you had when going up or down the stairs?" Participants responded about the amount of pain they experienced when going up or down stairs by using a NRS of 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain.

The SF-36 health survey is a self-administered questionnaire that measures each of the following 8 health domains: domain 1= general health, domain 2= physical function, domain 3= role physical, domain 4= bodily pain, domain 5= vitality, domain 6= social function, domain 7= role emotional, domain 8= mental health. Total score for each of the 8 domains were scaled from 0 (minimum) to 100 (maximum), where higher score indicated a better health related quality of life.

The SF-36 health survey is a self-administered questionnaire that measures each of the following 8 health domains: domain 1= general health, domain 2= physical function, domain 3= role physical, domain 4= bodily pain, domain 5= vitality, domain 6= social function, domain 7= role emotional, domain 8= mental health. Total score for each of the 8 domains were scaled from 0 (minimum) to 100 (maximum). These 8 domains are also summarized as 2 summary scores: mental component aggregate (MCA) and physical component aggregate (PCA). Total score range for each of the 2 summary scores =0 (minimum level of functioning) to 100 (maximum level of functioning). Higher (8 domains and 2 summary) scores indicate a better health related quality of life.

Median time to discontinuation due to lack of efficacy was estimated using Kaplan-Meier method.

In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day up to 3 days per week could be taken as rescue medication. Percentage of participants with any use of rescue medication during the specified study week were summarized.

In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day up to 3 days per week could be taken as rescue medication. Number of days participants used any of the rescue medication, during the specified week were summarized.

In case of inadequate pain relief for osteoarthritis, acetaminophen up to 4000 mg per day up to 3 days per week could be taken as rescue medication. The total dosage of acetaminophen in mg used during the specified week were summarized.

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 Week 24 that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.

Laboratory values: hematology (hemoglobin; hematocrit; red blood cell count [less than {<}0.8* lower limit of normal [LLN], platelets <0.5* LLN,>1.75* upper limit of normal (ULN), white blood cell count<0.6* LLN, >1.5* ULN, liver function (total bilirubin>1.5* ULN, aspartate aminotransferase; alanine aminotransferase; gamma-glutamyltransferase, lactate dehydrogenase, alkaline phosphatase>3.0* ULN, total protein; albumin<0.8* LLN; >1.2* ULN), renal function (blood urea nitrogen; creatinine>1.3* ULN, uric acid>1.2* ULN), lipids (cholesterol, triglycerides >1.3*ULN), electrolytes (sodium<0.95* LLN, >1.05* ULN; potassium; chloride; calcium; magnesium; phosphate; bicarbonate<0.9* LLN, >1.1* ULN), chemistry (glucose <0.6*LLN, >1.5*ULN; creatine kinase >2.0*ULN), urinalysis (specific gravity <1.003, >1.030; pH<4.5, >8, glucose; protein; blood; ketones; urobilinogen; bilirubin; nitrite, esterase>=1).

All standard intervals (PR, QRS, QT, QT interval corrected for heart rate using Fridericia's formula [QTcF], QT interval corrected for heart rate using Bazett's formula [QTcB], RR intervals and heart rate) were analyzed. Participants with abnormal ECG findings reported as treatment related adverse events were presented. Relatedness to treatment was assessed by investigator.

NIS is a standardized instrument used to evaluate participant for signs of peripheral neuropathy. NIS is the sum of scores of 37 items, where 24 items scored from 0 (normal function) to 4 (extreme abnormal function), higher score indicates higher abnormality and 13 items scored from 0 (normal function) to 2 (extreme abnormal function), higher score indicates higher abnormality. NIS possible overall score ranged from 0 (no impairment) to 122 (maximum impairment), higher scores indicated increased impairment.

Participants who developed anti-tanezumab antibodies after treatment were evaluated for the presence of anti-tanezumab neutralizing antibodies in their serum. Number of participants with positive ADA were summarized for reporting groups: Tanezumab 5 mg + Placebo and Tanezumab 10 mg + Placebo. Results with titer value >= 4.32 nanogram per milliliter of anti-tanezumab neutralizing antibodies were counted as positive.

Physical examination included an examination of the general appearance, skin, heart, head, eyes, ears, nose, throat, breasts, abdomen, musculoskeletal, neck, extremities, thyroid and others. Criteria for abnormal physical findings were based on investigator's discretion.

Vital signs included the assessment of the following: body temperature, blood pressure, heart rate and respiratory rate. Number of participants with clinically significant vital signs (based on the investigator's judgment) considered as adverse events were reported.