Tanezumab and Nerve Function In Arthritis Patients

5NC(nd)+HRdb(nd)composite score included 5 Nerve Conduction Studies(NCS)attributes(peroneal motor nerve distal latency \[MNDL\],peroneal nerve compound muscle action potential\[CMAP\],peroneal motor nerve conduction velocity\[MNCV\],tibial MNDL,sural sensory nerve action potential amplitude \[SNAP\])and HRdb value. Values of attributes scored as percentile(calculated from distribution of normal values corresponding to participant's baseline demographic characteristics),then expressed as normal deviate(nd)score based on standard normal distribution.Score \>0=worse response,less than(\<)0=better response compared to normal matched population.Score change\>0=worsening,\<0=improvement compared to baseline.2 neurological visits(NVs) were conducted both at baseline and Week 24. NCS measurements were collected once at each NV.HRdb measurements were collected twice and highest nd score was selected at each NV. Mean of selected measurements at each NV was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: Intent to treat (ITT) analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values were imputed using last observation carried forward (LOCF) method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

5NC(nd)+HRdb(nd)composite score included 5 Nerve Conduction Studies(NCS)attributes(peroneal motor nerve distal latency \[MNDL\],peroneal nerve compound muscle action potential\[CMAP\],peroneal motor nerve conduction velocity\[MNCV\],tibial MNDL,sural sensory nerve action potential amplitude \[SNAP\])and HRdb value. Values of attributes scored as percentile(calculated from distribution of normal values corresponding to participant's baseline demographic characteristics),then expressed as normal deviate(nd)score based on standard normal distribution.Score \>0=worse response,less than(\<)0=better response compared to normal matched population.Score change\>0=worsening,\<0=improvement compared to baseline.2 neurological visits(NVs) were conducted both at baseline and Week 24. NCS measurements were collected once at each NV.HRdb measurements were collected twice and highest nd score was selected at each NV. Mean of selected measurements at each NV was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: PPAS included all randomized participants who received at least 1 dose of intravenous study medication and excluded those who violated the exclusion criterion significant signs of neuropathy at baseline visits. Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

In case of inadequate pain relief for osteoarthritis during the treatment period, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Results reported is total dose of acetaminophen (in mg) for each week.

Time frame: Weeks 8, 16, and 24

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

SF-36v2 is a self-administered questionnaire evaluating 8 aspects/domains of functional health and wellbeing: physical function, role physical, bodily pain, vitality, general health, social function, role emotional and mental health. The total score for each domain is scaled 0-100 (100 = highest level of functioning). Change from baseline \>0 indicates an improvement.

Time frame: Baseline, Week 24

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

SF-36v2 is a self-administered questionnaire evaluating 8 aspects/domains of functional health and wellbeing: physical function, role physical, bodily pain, vitality, general health, social function, role emotional and 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. Change from baseline \>0 indicates an improvement.

Time frame: Baseline, Week 24

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

5NC (nd) score included 5 NCS attributes: peroneal MNDL, CMAP, MNCV, tibial MNDL and sural SNAP. Values of attributes scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Total score calculated as sum of each NCS attribute. Total score \>0 indicated worse and \<0 indicated better response as compared to normal matched population. Total score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

5NC (nd) score included 5 NCS attributes: peroneal MNDL, CMAP, MNCV, tibial MNDL and sural SNAP. Values of attributes scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Total score calculated as sum of each NCS attribute. Total score \>0 indicated worse and \<0 indicated better response as compared to normal matched population. Total score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline.2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: PPAS included all randomized participants who received at least 1 dose of intravenous study medication and excluded those who violated the exclusion criterion significant signs of neuropathy at baseline visits. Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

Participants assessed daily average index joint pain during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst pain). Higher score indicated greater pain.

Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 16, 17, 18, 19, 20, 21, 22, 23, and 24

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

HRdb test was used to evaluate the effect of treatment on autonomic function. Participants took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as a normal deviates. Score \<0 indicated worse response and \>0 indicated better response as compared to normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Measurements of HRdb were collected twice and highest nd score was selected at each NV. Mean of the 2 selected NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

HRdb test was used to evaluate the effect of treatment on autonomic function. Participants took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as a normal deviates. Score \<0 indicated worse response and \>0 indicated better response as compared to normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Measurements of HRdb were collected twice and highest nd score was selected at each NV. Mean of the 2 selected NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: PPAS included all randomized participants who received at least 1 dose of intravenous study medication and excluded those who violated the exclusion criterion significant signs of neuropathy at baseline visits. Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

NIS-LL: assess muscle weakness, reflexes, sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1 = decreased, or 2 = absent. NIS-LL score: sum of scores of NIS items 17-24, 28-29 and 34-37. Total possible NIS-LL score range 0-88, high score = more impairment.

Time frame: Baseline, Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each 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 possible NIS score range 0 to 244, higher score = greater impairment.

Time frame: Baseline, Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

NSC score is the number of the 38 symptom questions where the participants indicated experiencing the symptom to any severity. Total score range: 0 to 38 where higher score indicated more symptoms. A change from Baseline \> 0 indicated some symptoms of peripheral neuropathy.

Time frame: Baseline, Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

Peroneal motor nerve compound muscle action potential amplitude (in millivolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score \<0 indicated worse response and \>0 indicated better response than the normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the two NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

Peroneal motor nerve compound muscle action potential amplitude (in millivolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score \<0 indicated worse response and \>0 indicated better response than the normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: PPAS included all randomized participants who received at least 1 dose of intravenous study medication and excluded those who violated the exclusion criterion significant signs of neuropathy at baseline visits. Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

Peroneal motor nerve conduction velocity (in meters/second) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score \<0 indicated worse response and \>0 indicated better response than the normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

Peroneal motor nerve conduction velocity (in meters/second) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score \<0 indicated worse response and \>0 indicated better response than the normal matched population. Score change \<0 indicated worsening and \>0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: PPAS included all randomized participants who received at least 1 dose of intravenous study medication and excluded those who violated the exclusion criterion significant signs of neuropathy at baseline visits. Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

Peroneal motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score \>0 indicated worse response and \<0 indicated better response as compared to normal matched population. Score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

Peroneal motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score \>0 indicated worse response and \<0 indicated better response as compared to normal matched population. Score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: PPAS included all randomized participants who received at least 1 dose of intravenous study medication and excluded those who violated the exclusion criterion significant signs of neuropathy at baseline visits. Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

IENF density was quantified in 3 millimeter (mm) immunostained (PGP 9.5-immunohistochemical staining) skin punch biopsies taken from the distal end of the leg, 10 centimeter (cm) above the lateral malleolus, within the territory of the sural nerve, containing epidermis and superficial dermis to evaluate amount of small diameter nerve fibers. Skin biopsies were taken from normal appearing skin and skin having local scar, signs of trauma, ulceration, or active dermatologic process were avoided.

Time frame: Baseline, Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values imputed using LOCF. Here 'overall number of participants analyzed' signifies participants evaluable for this measure and 'number analyzed' signifies participants evaluable at specific time points for each arm, respectively.

Sural sensory nerve action potential amplitude (in microvolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. A score \<0 indicated worse response and \>0 indicated better response than the normal matched population. A change \<0 indicated worsening and \>0 indicated improvement compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values were imputed using LOCF method. Here 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

Sural sensory nerve action potential amplitude (in microvolts) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. A score \<0 indicated worse response and \>0 indicated better response than the normal matched population. A change \<0 indicated worsening and \>0 indicated improvement compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: PPAS included all randomized participants who received at least 1 dose of intravenous study medication and excluded those who violated the exclusion criterion significant signs of neuropathy at baseline visits. Missing values were imputed using LOCF method. Here, 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

Participants answered: Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today? Participants rated their condition 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.

Time frame: Baseline, Weeks 8, 16, and 24

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

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

Time frame: Baseline, Weeks 8, 16, and 24

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

WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in the index joint (knee or hip) 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.

Time frame: Baseline, Weeks 8, 16, and 24

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

Tibial motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score \>0 indicated worse response and \<0 indicated better response as compared to normal matched population. Score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of intravenous study medication (either tanezumab or matching placebo). Missing values were imputed using LOCF method. Here 'number analyzed' participants who were evaluable at specific time points for each arm, respectively.

Tibial motor nerve distal latency (in milliseconds) was measured using electromyography of the left lower limb. Values were scored as percentiles (calculated from distribution of normal values corresponding to participant's baseline demographic characteristics), then expressed as normal deviate (nd) score based on standard normal distribution. Score \>0 indicated worse response and \<0 indicated better response as compared to normal matched population. Score change \>0 indicated worsening and \<0 indicated improvement as compared to baseline. 2 neurological visits (NVs) were conducted both at baseline and Week 24. Mean of the 2 NV measurements was calculated to obtain Baseline and Week 24 values.

Time frame: Baseline, Week 24

Population: PPAS included all randomized participants who received at least 1 dose of intravenous study medication and excluded those who violated the exclusion criterion significant signs of neuropathy at baseline visits. Missing values were imputed using LOCF method. Here, 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively.

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 or 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. Change from baseline \<0 indicates an improvement.

Time frame: Baseline, Weeks 8, 16, and 24

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

The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to osteoarthritis in the index joint (knee or hip) 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 was defined as a sensation of decreased ease of movement in the index joint (knee or hip).

Time frame: Baseline, Weeks 8, 16, and 24

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

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. Change from baseline \<0 indicates an improvement.

Time frame: Baseline, Weeks 8, 16, and 24

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

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. Change from baseline \<0 indicated an improvement.

Time frame: Baseline, Weeks 8, 16, and 24

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

In case of inadequate pain relief for osteoarthritis during the treatment period, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication. Result reported is number of days of rescue medication use in each week, and ranges from 0 to 7.

Time frame: Weeks 8, 16, and 24

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

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. AEs included both serious AEs and non-serious AEs.

Time frame: Baseline through 112 days after last Intravenous dose of Investigational product to last participant treated with study medication on study (up to Week 32 after last IV dose of investigational product to last participant treated)

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

Human serum samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semiquantitative enzyme-linked immunosorbent assay (ELISA). Same participant may have positive ADA result at more than 1 time point.

Time frame: pre-dose on Day 1 (Baseline), Week 8, 16, 24, 32

Population: ITT analysis set. Here 'overall number of participants analyzed' signifies participants who were evaluable for this measure at any time point and 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively. This outcome was not planned to be analyzed for the 'placebo arm.

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) 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. Participants with specified reduction (as percent) from baseline at Week 16 are reported.

Time frame: Week 16

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

In case of inadequate pain relief for osteoarthritis during the treatment period, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication.

Time frame: Week 8, 16, 24

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

The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint ( knee or hip) in the past 48 hours. It is calculated as the mean of the scores from 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: Weeks 8, 16, and 24

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

Participants answered: Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today? Participants rated their condition 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.

Time frame: Weeks 8, 16, and 24

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

OMERACT-OARSI response: \>=50 percent (%) improvement from baseline and absolute change from baseline of \>=2 units 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 in 1) WOMAC pain subscale, 2) WOMAC physical function subscale, 3) PGA of osteoarthritis (score: 1-5, higher score=more affected). WOMAC pain, physical function subscales assess amount of pain/difficulty experienced (score: 0-10, higher score=higher pain/difficulty).

Time frame: Weeks 8, 16, and 24

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

Plasma trough concentration of tanezumab was measured using a validated, sensitive and specific enzyme-linked immunosorbent assay (ELISA).

Time frame: pre-dose on Day 1 (Baseline), Weeks 8, 16, 24, and 32

Population: ITT analysis set. Here 'overall number of participants analyzed' signifies participants who were evaluable for this measure at any time point and 'number analyzed' signifies participants who were evaluable at specific time points for each arm, respectively. This outcome was not planned to be analyzed for the 'placebo arm.

Number of participants are reported based on the maximum number of intravenous (IV) doses of either tanezumab or placebo received.

Time frame: Day 1 up to Week 24

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