Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Change From Baseline in the Daily Average Pain Intensity Numerical Rating Score (NRS) in the Index Bone Metastasis Cancer Pain Site at Week 8 |
Daily average pain intensity in the index bone metastasis cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores signified more severity of pain. The participants recorded their daily average pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on interactive response technology (IRT) diaries. Baseline daily average pain intensity value was mean of the daily average pain intensity NRS scores during the baseline assessment period prior to randomization. Baseline assessment period was up to 5 days prior to dosing. The Week 8 daily average pain intensity value was the mean of the daily average pain intensity NRS scores recorded for each of the 7 days prior to the Week 8. |
Baseline, Week 8 |
|
| Secondary |
Change From Baseline in the Daily Average Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 12, 16 and 24 |
Daily average pain intensity in the index bone metastasis cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain) where higher scores signified more severity of pain. The participants recorded their daily average pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline daily average pain intensity value was mean of the daily average pain intensity NRS scores during the baseline assessment period prior to randomization. Baseline assessment period was up to 5 days prior to dosing. The Weeks 1, 2, 4, 6, 12, 16 and 24 daily average pain intensity value was the mean of the daily average pain intensity NRS scores recorded for each of the 7 days prior to the each specified week. |
Baseline, Weeks 1, 2, 4, 6, 12, 16 and 24 |
|
| Secondary |
Change From Baseline in the Daily Worst Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
Daily worst pain intensity in the index bone metastasis cancer pain site is assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), higher scores signified more severity of pain. The participants describe their daily worst pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline daily worst pain intensity was mean of daily worst pain intensity NRS score during the baseline assessment period prior to randomization. Baseline assessment period was up to 5 days prior to dosing. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 daily worst pain intensity value was the mean of the daily worst pain intensity NRS scores recorded for each of the 7 days prior to the each specified week. |
Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
|
| Secondary |
Change From Baseline in the Weekly Average Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
Weekly average pain intensity in the non-index cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores signified more severity of pain. Non-index cancer pan sites were the most painful cancer pain sites other than the index bone metastasis cancer pain site. The participants described their weekly pain at the painful site by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline weekly average pain intensity was weekly average pain intensity NRS score recorded on any day during the baseline assessment period. Five days prior to dosing was considered as baseline assessment period. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 weekly average pain intensity value was the weekly average pain intensity NRS scores recorded on any day from the span of 7 days prior to specified week. |
Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
|
| Secondary |
Change From Baseline in the Weekly Worst Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
Weekly worst pain intensity in the non-index cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), higher scores signified more severity of pain. Non-index cancer pan sites were the most painful cancer pain sites other than the index bone metastasis cancer pain site. The participants describe their weekly worst pain at the painful site by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline weekly worst pain intensity was weekly worst pain intensity NRS score recorded on any day during the baseline assessment period. Five days prior to dosing was considered as baseline assessment period. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 weekly worst pain intensity value was the weekly worst pain intensity NRS scores which was recorded on any day from the span of 7 days prior to specified week. |
Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
|
| Secondary |
Change From Baseline in the Daily Average Pain Intensity NRS Score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
Daily average pain intensity in the non-index visceral cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores signified more severity of pain. The participants described their pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline is defined as the mean average daily pain intensity NRS score during the baseline assessment period prior to randomization. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value is the mean of the daily average pain intensity scores for the 7 days prior to the each specified week. |
Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
|
| Secondary |
Change From Baseline in the Daily Worst Pain Intensity NRS Score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
Daily worst pain intensity in the index bone metastasis cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores signified more severity of pain. The participants recorded their daily worst pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline pain intensity value was mean of the daily worst pain intensity NRS scores during the baseline assessment period prior to randomization. Baseline assessment period was up to 5 days prior to dosing. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value is the mean of the daily worst pain intensity scores for the 7 days prior to the each specified week. |
Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
|
| Secondary |
Number of Participants With Cumulative Reduction of >=30, 50, 70 and 90 Percent (%) From Baseline in Daily Average Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
Daily average pain intensity in the index bone metastasis cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores = more severity of pain. The participants recorded their daily average pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value = mean of the daily average pain intensity NRS scores for the 7 days prior to the each week. Number of participants with cumulative reduction of >= 30, 50, 70, and 90 % in daily average pain intensity NRS score in the index bone metastasis cancer pain site from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 were reported. Participants might be reported more than once in the specified rows for a time point. Rows with only non-zero data for cumulative reduction at specified time points, for at least 1 reporting arm, are reported below. |
Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
|
| Secondary |
Number of Participants With Reduction of >=30, 50, 70 and 90% From Baseline in Daily Worst Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
Daily worst pain intensity in the index bone metastasis cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores = more severity of pain. The participants recorded their daily worst pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value = mean of the daily worst pain intensity NRS scores for the 7 days prior to the each week. Number of participants with cumulative reduction of >= 30, 50, 70, and 90 % in daily worst pain intensity NRS score in the index bone metastasis cancer pain site from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 were reported. Participants might be reported more than once in the specified rows for a time point. Rows with only non-zero data for cumulative reduction at specified time points, for at least 1 reporting arm, are reported below. |
Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
|
| Secondary |
Change From Baseline in Participant's Global Assessment of Cancer Pain (PGA-CP) at Weeks 2, 4, 8, 16 and 24 |
Participants at specified time points, answered to the following question, "Considering all the ways your cancer pain affects you, how are you doing today?" on a Likert scale ranging from 1 to 5, on IRT diaries. Scores: 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 scores signified worsening of condition. |
Baseline, Weeks 2, 4, 8, 16 and 24 |
|
| Secondary |
Number of Participants With Reduction of >=2 Points From Baseline in PGA-CP Scores at Weeks 2, 4, 8, 16 and 24 |
Participants at specified time points, answered to the following question, "Considering all the ways your cancer pain affects you, how are you doing today?" on a Likert scale ranging from 1 to 5, on IRT diaries. Scores: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 scores signified worsening of condition. |
Baseline, Weeks 2, 4, 8, 16 and 24 |
|
| Secondary |
Average Daily Total Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
In this outcome measure average daily opioid consumption was reported in milligram of morphine equivalent dose (mg of MED). |
Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
|
| Secondary |
Average Number of Doses of Rescue Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
In this outcome measure average number of doses of rescue opioid consumption at specified time points were reported. |
Weeks 1, 2, 4, 6, 8, 12, 16 and 24 |
|
| Secondary |
Change From Baseline in the Weekly Opioid-Related Symptom Distress Scale (OR-SDS) at Weeks 2, 4, 8, 16, and 24 |
OR-SDS: questionnaire evaluated opioid-related 12 symptoms. For each symptom, participants assigned integer scores to assess severity (none =0 to very severe =4), distress (none =0 to very much =5), and frequency (none =0 to almost constantly =4; participants reported number of retching/vomiting episodes (none =0, 1-2 episodes =1, 3-4 episodes =2, 5-6 episodes =3, >6 episodes =4). Frequency composite score: mean of frequency scores from all symptoms, ranged from 0 (none) to 4 (almost constantly); higher scores = worse condition. Severity composite score: mean of severity scores from all 12 symptoms, ranged from 0 (none) to 4 (maximum severity); higher scores = worse condition. Distress composite score: mean of distress scores from all 12 symptoms, ranged from 0 (none) to 5 (maximum distress); higher scores = worse condition. Multi domain average (MDA): average of each symptom for frequency, severity, and distress; ranged from 0 (none) to 4.34 (worse); higher scores = worse condition. |
Baseline, Weeks 2, 4, 8, 16, and 24 |
|
| Secondary |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (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 post last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and all non-serious AEs. Participants were followed up to 24 weeks after study drug last dose. |
Day 1 of dosing up to 24 weeks post last dose (maximum up to Week 48) |
|
| Secondary |
Number of Participants With Laboratory Abnormalities (Normal Baseline) |
Laboratory 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; leukocytes<0.6*LLN, >1.5*ULN; lymphocytes, neutrophils <0.8*LLN, >1.2*ULN; basophils, eosinophils, monocytes >1.2*ULN; total bilirubin>1.5*ULN; activated partial thromboplastin time, prothrombin time, prothrombin intl. normalized ratio >1.1*ULN; bilirubin >1.5*ULN; aspartate aminotransferase (AT), alanine AT, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase >3.0*ULN; protein; albumin<0.8*LLN, >1.2*ULN; 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; Urine: glucose, ketones, protein, HGB, bilirubin, nitrite >=1. |
Baseline (Day 1, before dosing) up to Week 48 |
|
| Secondary |
Number of Participants With Laboratory Abnormalities (Abnormal Baseline) |
Laboratory abnormality criteria included: HGB; hematocrit; erythrocytes < 0.8* 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; leukocytes <0.6*LLN, >1.5*ULN; lymphocytes, neutrophils <0.8*LLN, >1.2*ULN; basophils, eosinophils, monocytes >1.2*ULN; activated partial thromboplastin time, prothrombin time >1.1*ULN; bilirubin>1.5*ULN; aspartate AT, alanine AT, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase >3.0*ULN; protein; albumin<0.8*LLN, >1.2*ULN; urea nitrogen, 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; creatine kinase >2.0*ULN. |
Baseline (Day 1, before dosing) up to Week 48 |
|
| Secondary |
Number of Participants With Categorical Change From Baseline to Last Post-Baseline in Sitting Systolic and Diastolic Blood Pressure During Treatment Period |
Change categories for sitting systolic blood pressure measured in millimeter of mercury (mm Hg) were as follows: change <=-40, change >-40 to -30, change >-30 to -20, change >-20 to -10, change >-10 to 0, change >0 to <10, change >=10 to <20, change >=20 to <30, change >=30 to <40 and change >=40. Change categories for sitting diastolic blood pressure measured in mm Hg were as follow: change <=-30, change >-30 to -20, change >-20 to -10, change >-10 to 0, change >0 to <10, change >=10 to <20, change >=20 to <30 and change >=30. Rows with only non-zero data/values, for at least 1 reporting arm, are reported below. |
Baseline (Day 1, before dosing) up to Week 24 |
|
| Secondary |
Number of Participants With Categorical Summary of Electrocardiogram (ECG) (QTC) Data |
Electrocardiogram assessment included QT interval corrected using Fridericia's formula (QTcF), QT interval corrected using Bazett's formula (QTcB), both had following categories: 450<=Value<480 millisecond (msec), 480<=Value<500 msec and Value>=500 msec. |
Baseline (Day 1, before dosing) up to Week 24 |
|
| Secondary |
Number of Participants With Confirmed Orthostatic Hypotension |
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. |
Baseline (Day 1, before dosing), Weeks 8, 16, 24 and 48 |
|
| Secondary |
Number of Participants With Clinically Significant Findings in Weight Measurement, Counted as an AE |
The number of participants with clinically significant findings in weight measurement and were counted as an AE in the study were reported in this outcome measure. |
Day 1 of dosing up to maximum of Week 48 |
|
| Secondary |
Number of Participants With Abnormal Physical Examination at Screening |
Physical examination included assessment of general, head, eyes, ears, nose, neck, thyroid, lungs, heart, abdomen, extremities, skin, throat and other. Investigator judged abnormality in physical examinations. |
Screening (up to 37 days prior to Day 1) |
|
| Secondary |
Number of Participants With Individual Adjudicated Joint Safety Outcome/Event |
Joint-related safety events resulting in total joint replacement and/or discontinuation from the study as well as adverse events were reviewed by the External Adjudication Committee to confirm the potential events as adjudicated join safety event. In this outcome measure, number of participants with any of the joint safety adjudication outcomes of primary osteonecrosis, rapidly progressive osteoarthritis (OA) (type 1 and type 2), subchondral insufficiency fracture (or SPONK), or pathological fracture were reported. Other adjudication outcomes included normal progression of OA and other joint outcome. |
During the study, maximum up to Week 48 |
|
| Secondary |
Number of Participants With At Least 1 Total Joint Replacements (TJR) |
Number of participants with joint replacement surgery were reported. |
During the study, maximum up to Week 48 |
|
| Secondary |
Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Anti-Drug Antibodies (NAb) |
Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using a semi quantitative enzyme linked immunosorbent assay (ELISA). Number of participants with presence of anti-tanezumab antibodies and neutralizing anti-drug antibodies are reported. |
Baseline (Day 1, before dosing) up to Week 48 |
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