Tanezumab In Osteoarthritis Of The Hip Or Knee

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis (OA) in the index joint (knee/hip) during 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.

Time frame: Baseline, Week 8

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using last observation carried forward (LOCF).

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA in the index joint (knee/hip) during past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on an 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.

Time frame: Baseline, Week 8

Population: Modified intent-to-treat (mITT) analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the United States Food and Drug Administration \[US FDA\] imposed clinical hold). Missing data were imputed using LOCF.

In the event of inadequate pain relief for OA during the double-blind treatment period, participants were allowed to take up to 3000 mg of acetaminophen (tablet/capsule/caplets) per day up to 3 days per week as a rescue medication. Results are presented as total dose of acetaminophen (in mg) per week.

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

Population: ITT analysis set. Missing data were imputed using LOCF. Here 'overall number of participants analyzed' signifies participants who were evaluable for this measure and 'number analyzed' signifies participants who were evaluable at specified time-point for each treatment arm, respectively.

SF-36v2: standardized survey evaluating 8 health concepts (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health). Total score for each health concept was scaled 0-100 (100 = highest level of functioning).

Time frame: Baseline, Week 12

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using baseline observation carried forward (BOCF).

SF-36v2: standardized survey evaluating 8 health concepts (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health). Total score for each health concept was scaled 0-100 (100 = highest level of functioning).

Time frame: Baseline, Week 12

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using BOCF.

SF-36v2: standardized survey evaluating 8 health concepts (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health). Total score for each health concept was 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. Change from baseline \>0 indicates an improvement.

Time frame: Baseline, Week 12

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using BOCF.

SF-36v2: standardized survey evaluating 8 health concepts (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health). Total score for each health concept was 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. Change from baseline \>0 indicates an improvement.

Time frame: Baseline, Week 12

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using BOCF.

Participants assessed daily average pain in the index joint (knee/hip) during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). Higher score indicated greater pain. The baseline mean was calculated using the daily pain scores in the index joint (knee/hip) over the 3 days in the initial pain assessment period and the weekly mean was calculated using the daily pain scores in the index joint (knee/hip) within each assessment week.

Time frame: Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12, and 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using LOCF. Here 'overall number of participants analyzed' signifies those participants who were evaluable for this measure.

Participants assessed daily average pain in the index joint (knee/hip) during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). Higher score indicated greater pain. The baseline mean was calculated using the daily pain scores in the index joint (knee/hip) over the 3 days in the initial pain assessment period and the weekly mean was calculated using the daily pain scores in the index joint (knee/hip) within each assessment week.

Time frame: Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12, and 16

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using LOCF. Here 'overall number of participants analyzed' signifies those participants who were evaluable for this measure.

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains/items: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each item has 3 possible responses: no problems (level 1), some problems (level 2), and extreme problems (level 3). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

Time frame: Baseline, Week 12

Population: ITT analysis set. Here 'overall number of participants analyzed' signifies participants who were evaluable for this measure and 'number analyzed' signifies participants who were evaluable at specified time-point for each treatment arm, respectively.

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains/items: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each item has 3 possible responses: no problems (level 1), some problems (level 2), and extreme problems (level 3). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

Time frame: Baseline, Week 12

Population: mITT analysis set. Here 'overall number of participants analyzed' signifies participants who were evaluable for this measure and 'number analyzed' signifies participants who were evaluable at specified time-point for each treatment arm, respectively.

NIS: 74 items, assess muscle weakness, reflexes and sensation; scored separately for left, right limbs (37 items for each side). Components of muscle weakness are 24 items and scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes and sensation are 13 items and scored 0 = normal, 1= decreased, or 2 = absent. Total NIS score is the sum of the left and right limb scores. Total possible NIS score range 0 to 244, higher score=greater impairment.

Time frame: Baseline, Weeks 2, 4, 8, 12, 16, and 18

Population: ITT analysis set. Missing data were imputed using LOCF. Here 'number analyzed' signifies participants who were evaluable at specified time-point for each treatment arm, respectively.

PGA: Participants answered the following question: Considering all the ways the OA in your index (knee/hip) affects you, how are you doing today? Participants rated their condition by using a 5-point Likert scale: 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.

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

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using LOCF.

PGA: Participants answered the following question: Considering all the ways the OA in your index (knee/hip) affects you, how are you doing today? Participants rated their condition by using a 5-point Likert scale: 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.

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

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using LOCF.

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 OA of the index knee or index hip. WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher score indicates worse response.

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

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using LOCF.

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 OA of the index knee or index hip. WOMAC average score is the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher score indicates worse response.

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

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using LOCF.

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA in the index joint (knee/hip) during past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on an 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.

Time frame: Baseline, Weeks 2, 4, 12, and 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using LOCF.

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA in the index joint (knee/hip) during past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on an 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.

Time frame: Baseline, Weeks 2, 4, 12, and 16

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using LOCF.

The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in the index joint (knee/hip) during past 48 hours. It is calculated as the mean of the scores from the 17 individual questions scored on an 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. 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, and 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using LOCF. Here 'overall number of participants analyzed' signifies those participants who were evaluable for this measure.

The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in the index joint (knee/hip) during past 48 hours. It is calculated as the mean of the scores from the 17 individual questions scored on an 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. Physical function refers to participant's ability to move around and perform usual activities of daily living.

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

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using LOCF. Here 'overall number of participants analyzed' signifies those participants who were evaluable for this measure.

The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to OA in the index joint (knee/hip) during 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 moving the index joint (knee/hip).

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

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using LOCF.

The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to OA in the index joint (knee/hip) during 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 moving the index joint (knee/hip).

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

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using LOCF.

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.

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

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using LOCF.

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.

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

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using LOCF.

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.

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

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using LOCF.

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.

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

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using LOCF.

In the event of inadequate pain relief for OA during the double-blind treatment period, participants were allowed to take up to 3000 mg of acetaminophen (tablet/capsule/caplets) per day up to 3 days per week as a rescue medication. Results are shown in number of days of rescue medication usage per week.

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

Population: ITT analysis set. Missing data were imputed using LOCF. Here 'overall number of participants analyzed' signifies participants who were evaluable for this measure and 'number analyzed' signifies participants who were evaluable at specified time-point for each treatment arm, respectively.

Time frame: Baseline up to Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo).

Adverse event of abnormal peripheral sensation: allodynia, burning sensation, decreased vibratory sense, dysaesthesia, hyperaesthesia, hyperpathia, hypoaesthesia, neuralgia, neuritis, neuropathy peripheral, pallanesthesia, paraesthesia, paraesthesia oral, peripheral sensory neuropathy, polyneuropathy, sensory disturbance, sensory loss and thermohypoaesthesia. Adverse event of abnormal peripheral sensation was assessed according to severity: mild (did not interfere with participant's usual function); moderate (interfered to some extent with participant's usual function); and severe (interfered significantly with participant's usual function).

Time frame: Baseline up to 112 days after last intravenous dose

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo).

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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. AEs included SAEs as well as non-serious AEs which occurred during the trial.

Time frame: Baseline up to 112 days after last intravenous dose

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo).

Human serum samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative enzyme-linked immunosorbent assay (ELISA). Only participants receiving tanezumab were to be analyzed for this measure. A participant may be represented in more than 1 category.

Time frame: Baseline, Week 8 and 18

Population: ITT analysis set. Here 'overall number of participants analyzed' signifies participants who were evaluable for this measure and 'number analyzed' signifies participants who were evaluable at specified time-point for each treatment arm, respectively.

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA in the index joint (knee/hip) during past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on an 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.

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

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using LOCF.

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA in the index joint (knee/hip) during past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on an 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.

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

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using LOCF.

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 dimensions/domains/items: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each item has 3 possible responses: no dysfunction (level 1), moderate/some dysfunction (level 2), and extreme dysfunction (level 3). Change from baseline at Week 12 is defined as: Improved (positive change), No change, and Worsened (negative change). Number of participants with response is reported.

Time frame: Baseline, Week 12

Population: ITT analysis set. Here 'overall number of participants analyzed' signifies participants who were evaluable for this measure and 'number analyzed' signifies participants who were evaluable at specified time-point for each treatment arm, respectively.

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 dimensions/domains/items: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each item has 3 possible responses: no dysfunction (level 1), moderate/some dysfunction (level 2), and extreme dysfunction (level 3). Change from baseline at Week 12 is defined as: Improved (positive change), No change, and Worsened (negative change). Number of participants with response is reported.

Time frame: Baseline, Week 12

Population: mITT analysis set. Here 'overall number of participants analyzed' signifies participants who were evaluable for this measure and 'number anlayzed' signifies participants who were evaluable at specified time-point for each treatment arm, respectively.

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA in the index joint (knee/hip) during the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on an 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 8 are reported.

Time frame: Week 8

Population: ITT analysis set included all randomized participants who received at least 1 dose of randomized intravenous study medication (either tanezumab or placebo). Missing data were imputed using LOCF.

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA in the index joint (knee/hip) during past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on an 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.

Time frame: Week 8

Population: mITT analysis set included all participants in ITT analysis set who had Week 8 visit on or before 23 June 2010 (effective date of the US FDA imposed clinical hold). Missing data were imputed using LOCF.