Tanezumab In Osteoarthritis Of The Knee (2)

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 2, 4, 8 and 12: Baseline Observation Carried Forward (BOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain.

Time frame: Baseline, Week 2, 4, 8, 12

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 2, 4, 8 and 12: Last Observation Carried Forward (LOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain.

Time frame: Baseline, Week 2, 4, 8, 12

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 2, 4, 8 and 12: Baseline Observation Carried Forward (BOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee joint during past 48 hours. It is calculated as mean of the scores from 17 individual questions scored on a numerical rating scale of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate more difficulty. An overall possible WOMAC physical function subscale score range is of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate worse function. Physical function refers to participant's ability to move around and perform usual activities of daily living.

Time frame: Baseline, Week 2, 4, 8, 12

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 2, 4, 8 and 12: Last Observation Carried Forward (LOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee joint during past 48 hours. It is calculated as mean of the scores from 17 individual questions scored on a numerical rating scale of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate more difficulty. An overall possible WOMAC physical function subscale score range is of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate worse function. Physical function refers to participant's ability to move around and perform usual activities of daily living.

Time frame: Baseline, Week 2, 4, 8, 12

Change From Baseline in Patient Global Assessment of Osteoarthritis at Week 2, 4, 8 and 12: Baseline Observation Carried Forward (BOCF)

Participants answered: "Considering all the ways the osteoarthritis in your index knee affects you, how are you doing today?" Participants responded on the scale ranging from 1 (minimum affected) to 5 (maximum affected), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicate worse condition.

Time frame: Baseline, Week 2, 4, 8, 12

Change From Baseline in Patient Global Assessment of Osteoarthritis at Week 2, 4, 8 and 12: Last Observation Carried Forward (LOCF)

Participants answered: "Considering all the ways the osteoarthritis in your index knee affects you, how are you doing today?" Participants responded on the scale ranging from 1 (minimum affected) to 5 (maximum affected), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicate worse condition.

Time frame: Baseline, Week 2, 4, 8, 12

Percentage of Responders For Outcome Measures in Rheumatology- Osteoarthritis Research Society International (OMERACT-OARSI): Baseline Observation Carried Forward (BOCF)

A participant was considered as an 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 or physical function subscale; if improvement from baseline to week of interest was \>=20 percent and \>=1 unit in at least 2 of the following: a) WOMAC pain subscale, b) WOMAC physical function subscale, c) PGA of osteoarthritis. WOMAC pain subscale assess amount of pain experienced (score: 0 \[minimum pain\] to 10 \[maximum pain\], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 \[minimum difficulty\] to 10 \[maximum difficulty\], higher score = higher difficulty) and PGA of osteoarthritis (score: 1 \[minimum affected\] to 5 \[maximum affected\], higher score = worse condition). Percentage of participants who were OMERACT-OARSI responder were reported in this outcome measure.

Time frame: Weeks 2, 4, 8, 12, 16

Percentage of Responders For Outcome Measures in Rheumatology- Osteoarthritis Research Society International (OMERACT-OARSI): Last Observation Carried Forward (LOCF)

A participant was considered as an 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 or physical function subscale; if improvement from baseline to week of interest was \>=20 percent and \>=1 unit in at least 2 of the following: a) WOMAC pain subscale, b) WOMAC physical function subscale, c) PGA of osteoarthritis. WOMAC pain subscale assess amount of pain experienced (score: 0 \[minimum pain\] to 10 \[maximum pain\], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 \[minimum difficulty\] to 10 \[maximum difficulty\], higher score = higher difficulty) and PGA of osteoarthritis (score: 1 \[minimum affected\] to 5 \[maximum affected\], higher score = worse condition). Percentage of participants who were OMERACT-OARSI responder were reported in this outcome measure.

Time frame: Week 2, 4, 8, 12, 16

Percentage of Participants With at Least 30 Percent, and 50 Percent Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale: Baseline Observation Carried Forward (BOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. Percentage of participants with at least 30 percent and 50 percent reduction in WOMAC pain subscale were reported in this outcome measure.

Time frame: Week 2, 4, 8, 12, 16

Percentage of Participants With at Least 30 Percent, and 50 Percent Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale: Last Observation Carried Forward (LOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. Percentage of participants with at least 30 percent and 50 percent reduction in WOMAC pain subscale were reported in this outcome measure.

Time frame: Week 2, 4, 8, 12, 16

Percentage of Participants With at Least 2 Points Improvement From Baseline in Patient Global Assessment (PGA) of Osteoarthritis: Baseline Observation Carried Forward (BOCF)

Participants answered: "Considering all the ways the osteoarthritis in your index knee affects you, how are you doing today?" Participants responded on the scale ranging from 1 (minimum affected) to 5 (maximum affected), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicate worse condition. Percentage of participants with at least 2 points improvement from baseline in PGA of osteoarthritis at specified weeks were reported.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Percentage of Participants With at Least 2 Points Improvement From Baseline in Patient Global Assessment (PGA) of Osteoarthritis: Last Observation Carried Forward (LOCF)

Participants answered: "Considering all the ways the osteoarthritis in your index knee affects you, how are you doing today?" Participants responded on the scale ranging from 1 (minimum affected) to 5 (maximum affected), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicate worse condition. Percentage of participants with at least 2 points improvement from baseline in PGA of osteoarthritis at specified weeks were reported.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Percentage of Participants With Cumulative Reduction From Baseline up to Week 16 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score: Baseline Observation Carried Forward (BOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. Percentage of participants with cumulative reduction (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.

Time frame: Baseline up to Week 16

Percentage of Participants With Cumulative Reduction From Baseline up to Week 16 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score: Last Observation Carried Forward (LOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It is calculated as mean of the scores from 5 individual questions scored on a numerical rating scale of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. An overall possible WOMAC pain subscale score range is of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain. Percentage of participants with cumulative reduction (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.

Time frame: Baseline up to Week 16

Change From Baseline for the Average Pain Score in the Index Knee at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)

Participants assessed daily average pain score in the index knee using a scale ranging from 0 (no pain) to 10 (maximum pain), where higher scores indicate more pain. A weekly mean was calculated using the daily average index knee pain scores within each specified study week.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Change From Baseline for the Average Pain Score in the Index Knee at Week 2, 4, 8, 12 and 16: Last Observation Carried Forward (LOCF)

Participants assessed daily average pain score in the index knee using a scale ranging from 0 (no pain) to 10 (maximum pain), where higher scores indicate more pain. A weekly mean was calculated using the daily average index knee pain scores within each specified study week.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in knee joint during past 48 hours. It is calculated as mean of the scores from 2 individual questions each scored on numerical rating scale of 0 (minimum stiffness) to 10 (maximum stiffness), where higher scores indicate greater stiffness. An overall possible WOMAC stiffness subscale score range is of 0 (minimum stiffness) to 10 (maximum stiffness), where higher scores indicate higher stiffness. Stiffness is defined as a sensation of decreased ease in moving the index knee.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 2, 4, 8, 12 and 16: Last Observation Carried Forward (LOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in knee joint during past 48 hours. It is calculated as mean of the scores from 2 individual questions each scored on numerical rating scale of 0 (minimum stiffness) to 10 (maximum stiffness), where higher scores indicate greater stiffness. An overall possible WOMAC stiffness subscale score range is of 0 (minimum stiffness) to 10 (maximum stiffness), where higher scores indicate higher stiffness. Stiffness is defined as a sensation of decreased ease in moving the index knee.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale assess amount of pain experienced (score: 0 \[minimum pain\] to 10 \[maximum pain\], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 \[minimum difficulty\] to 10 \[maximum difficulty\], higher score = higher difficulty) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 \[minimum stiffness\] to 10 \[maximum stiffness\], higher score = higher stiffness). WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores, giving an overall possible WOMAC average score range of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate worse response.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 2, 4, 8, 12 and 16: Last Observation Carried Forward (LOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. WOMAC pain subscale assess amount of pain experienced (score: 0 \[minimum pain\] to 10 \[maximum pain\], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 \[minimum difficulty\] to 10 \[maximum difficulty\], higher score = higher difficulty) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 \[minimum stiffness\] to 10 \[maximum stiffness\], higher score = higher stiffness). WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores, giving an overall possible WOMAC average score range of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicate worse response.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score When Walking on a Flat Surface at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. Participants responded by using a numerical rating scale of 0 (no pain) to 10 (maximum pain) about the amount of pain they experienced when walking on a flat surface, where 0= no pain and 10= extreme pain. Higher score indicates more pain.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score When Walking on a Flat Surface at Week 2, 4, 8, 12 and 16: Last Observation Carried Forward (LOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. Participants responded by using a numerical rating scale of 0 (no pain) to 10 (maximum pain) about the amount of pain they experienced when walking on a flat surface, where 0= no pain and 10= extreme pain. Higher score indicates more pain.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score When Going Up or Down Stairs at Week 2, 4, 8, 12 and 16: Baseline Observation Carried Forward (BOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. Participants responded by using a numerical rating scale of 0 (no pain) to 10 (maximum pain) about the amount of pain they experienced when going up or down stairs, where 0= no pain and 10= extreme pain. Higher score indicates more pain.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score When Going Up or Down Stairs at Week 2, 4, 8, 12 and 16: Last Observation Carried Forward (LOCF)

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms in participants with osteoarthritis of knee. Participants responded by using a numerical rating scale of 0 (no pain) to 10 (maximum pain) about the amount of pain they experienced when going up or down stairs, where 0= no pain and 10= extreme pain. Higher score indicates more pain.

Time frame: Baseline, Week 2, 4, 8, 12, 16

Change From Baseline in Short-Form 36 Health Survey (SF-36) 8 Health Domains, Mental Component Aggregate and Physical Component Aggregate Scores at Week 12 and 16: Baseline Observation Carried Forward (BOCF)

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 and domain 8= mental health. Total score for each of the 8 domains are scaled from 0 (minimum level of functioning) to 100 (maximum level of functioning). 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.

Time frame: Baseline, Week 12, 16

Change From Baseline in Short-Form 36 Health Survey (SF-36) 8 Health Domains, Mental Component Aggregate and Physical Component Aggregate Scores at Week 12 and 16: Last Observation Carried Forward (LOCF)

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 and domain 8= mental health. Total score for each of the 8 domains are scaled from 0 (minimum level of functioning) to 100 (maximum level of functioning). 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.

Time frame: Baseline, Week 12, 16

Time to Discontinuation Due to Lack of Efficacy

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

Time frame: Baseline up to Week 16

Percentage of Participants Who Used Rescue Medication

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

Time frame: Week 2, 4, 8, 12, 16

Number of Days Participants Used Rescue Medication

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

Time frame: Week 2, 4, 8, 12, 16

Amount of Rescue Medication Taken

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

Time frame: Week 2, 4, 8, 12, 16