Celecoxib+ Exemestane

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. Treatment-emergent were events between first dose of study drug and up to 24 weeks after last dose of study drug (up to Week 80) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.

Treatment-related AE was any untoward medical occurrence attributed to study drug in participant who received study drug. 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 were events between first dose of study drug and up to 24 weeks after last dose of study drug (up to Week 80). Relatedness to study drug was assessed by the investigator. AEs included both serious and non-serious AEs.

Abnormality criteria included: hemoglobin (HGB); hematocrit; erythrocytes \< 0.8\*lower limit of normal (LLN); erythrocyte mean corpuscular volume/HGB/ HGB concentration, erythrocytes distribution width \<0.9\*LLN, \>1.1\*upper limit of normal (ULN); platelets \<0.5\*LLN,\>1.75\* ULN; white blood cell count\<0.6\*LLN, \>1.5\*ULN; lymphocytes, leukocytes, neutrophils \<0.8\*LLN, \>1.2\*ULN; basophils, eosinophils, monocytes \>1.2\*ULN; total bilirubin\>1.5\*ULN; aspartate aminotransferase (AT), alanine AT, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase \>3.0\*ULN; total protein; albumin\<0.8\*LLN, \>1.2\*ULN; blood urea nitrogen, creatinine, cholesterol, triglycerides \>1.3\*ULN; urate \>1.2\*ULN; sodium \<0.95\*LLN,\>1.05\*ULN; potassium, chloride, calcium, magnesium, bicarbonate \<0.9\*LLN, \>1.1\*ULN; phosphate \<0.8\*LLN, \>1.2\*ULN; glucose \<0.6\*LLN, \>1.5\*ULN; HGB A1C \>1.3\*ULN; creatine kinase \>2.0\*ULN; nitrite \>=1. Investigator judged clinical significance of laboratory test abnormalities.

Vital signs included systolic blood pressure, diastolic blood pressure and pulse rate. Investigator judged clinical significance of vital signs' abnormalities.

Orthostatic hypotension was defined as postural change (supine to standing) that met the following criteria: for systolic blood pressure (BP) less than or equal to (\<=) 150 millimeter of mercury (mmHg) (mean supine): reduction in systolic BP \>=20 mmHg or reduction in diastolic BP \>=10 mmHg at the 1 and/or 3 minute standing BP measurements. For systolic BP greater than (\>) 150 mmHg (mean supine): reduction in systolic BP \>=30 mmHg or reduction in diastolic BP \>=15 mmHg at the 1 and/or 3 minute standing BP measurements. If the 1 minute or 3 minute standing BP in a sequence met the orthostatic hypotension criteria, then that sequence was considered positive. If 2 of 2 or 2 of 3 sequences were positive, then orthostatic hypotension was considered confirmed.

SAS is a participant rated 12 items questionnaire for males and 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during the past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants were asked to answer "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If a participant answered "Yes" for a symptom, then impact of that symptom was rated on a 5 point scale, ranged from 1 (least sever impact) to 5 (most severe impact), where higher scores signified more severe impact of symptoms. The total symptom impact score was calculated as the sum of impact of all symptoms. Overall possible range for the total symptom impact score was 0 (no impact) to 60 (extreme impact) for males and 0 (no impact) to 55 (extreme impact) for females, higher scores indicated more severe impact of symptoms on participants' well-being.

SAS is a participant rated 12 items questionnaire for males and 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during the past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants were asked to answer "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If a participant answered "Yes" for a symptom, then impact of that symptom was rated on a 5 point scale, ranged from 1 (least sever impact) to 5 (most severe impact), where higher scores signified more severe impact of symptoms. The total symptom impact score was calculated as the sum of impact of all symptoms. Overall possible range for the total symptom impact score was 0 (no impact) to 60 (extreme impact) for males and 0 (no impact) to 55 (extreme impact) for females, higher scores indicated more severe impact of symptoms on participants' well-being.

SAS is a participant rated 12 items questionnaire for males and 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during the past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants were asked to answer "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If a participant answered "Yes" for a symptom, then impact of that symptom was rated on a 5 point scale, ranged from 1 (least sever impact) to 5 (most severe impact), where higher scores signified more severe impact of symptoms. The total symptom impact score was calculated as the sum of impact of all symptoms. Overall possible range for the total symptom impact score was 0 (no impact) to 60 (extreme impact) for males and 0 (no impact) to 55 (extreme impact) for females, higher scores indicated more severe impact of symptoms on participants' well-being.

SAS: participant rated 12 items questionnaire for males; 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants answered "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If participant answered "Yes" for a symptom, then impact of that symptom was rated on 5 point scale (1 \[least sever impact\] to 5 \[most severe impact\]); higher scores = more severe impact of symptoms. Total impact score = sum of impact of all symptoms; range for males =0 (no impact) to 60 (extreme impact); females =0 (no impact) to 55 (extreme impact); higher scores = more severe impact of symptoms on participants' well-being. Participants discontinuing from study treatment before Week 56, had early termination follow-up visit 1 at 8 weeks after last dose of tanezumab or placebo matched to tanezumab.

SAS: participant rated 12 items questionnaire for males; 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants answered "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If participant answered "Yes" for a symptom, then impact of that symptom was rated on 5 point scale (1 \[least sever impact\] to 5 \[most severe impact\]); higher scores = more severe impact of symptoms. Total impact score = sum of impact of all symptoms; range for males =0 (no impact) to 60 (extreme impact); females =0 (no impact) to 55 (extreme impact); higher scores = more severe impact of symptoms on participants' well-being. Participants discontinuing from study treatment before Week 56, had early termination follow-up visit 3 at 24 weeks after last dose of tanezumab or placebo matched to tanezumab.

Electrocardiogram assessment included PR, QRS, QT, QT interval corrected using Fridericia's formula (QTcF), QT interval corrected using Bazett's formula (QTcB), RR intervals, and heart rate. Investigator judged clinical significance of electrocardiogram assessment.

Percentage of participants with individual joint safety adjudication outcomes: rapidly progressive osteoarthritis (OA) type-1 only, rapidly progressive OA type-2 only, primary osteonecrosis, pathological fracture and subchondral insufficiency fracture is reported. Rapidly progressive (RP) OA type 1 events were those that the adjudication committee considered to have significant loss of joint space width \>= 2 millimeter within approximately 1 year without gross structural failure. RP OA type 2 events were those considered to have destruction of bone including limited or total collapse of at least 1 subchondral surface that is not normally present in conventional end-stage osteoarthritis. Subchondral insufficiency fractures are a type of stress fractures which occur below the cartilage on the weight bearing surface of a bone.

Individual adjudicated joint safety outcomes/event: rapidly progressive OA (type-1,type-2), primary osteonecrosis, pathological fracture and subchondral insufficiency fracture. Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Event rate for any individual adjudicated joint safety outcome/event = the number of events per 1000 participant-years at risk.

Percentage of participants with at least 1 total knee, total hip or total shoulder joint replacement were reported.

Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant had no TJR, or (ii) date of TJR (earliest TJR within each participant in the case of multiple TJRs). Event rate = number of events per 1000 participant-years at risk.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits. Largest change from baseline here means worst post- baseline change value (among all change from baseline values).

Human serum samples were analyzed for the presence or absence of anti-tanezumab antibodies by using a validated analytical method. Number of participants with presence of anti-tanezumab antibodies are reported.

Physical examination included assessment of general appearance, skin, head, neck, eyes, ears, nose, throat, abdomen, lungs, heart, thyroid, and extremities. Investigator judged abnormality in physical examinations. Only those rows have been reported which had at least 1 participant with abnormality data in any of the reporting arms.