A Study of Tanezumab in Adults With Chronic Low Back Pain

RMDQ: back-specific, participant administered questionnaire that assesses how well participants with low back pain were able to function with regard to daily activities. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement if it describes his/her functional ability on the day of assessment. The number of statements marked are added up by the clinician. Total RMDQ score is calculated as the sum of number of statements marked. Total possible RMDQ score: 0 (best functioning) to 24 (worst functioning), with higher scores indicated greater disability.

Participants answered: "Considering all ways your low back pain affects you, how are you doing today?" Participants rated their condition using scale assessing symptoms and limitations to carry out normal daily activities. Score range:1 to 5. 1: Very Good (No symptoms and limitations); 2: Good (Mild symptoms and no limitations); 3: Fair (Moderate symptoms and some limitations); 4: Poor (Severe symptoms and inability to carry out most activities); 5: Very Poor (Very severe, intolerable symptoms and inability to carry all activities).

Daily average back pain was assessed on an 11-point numeric rating scale (NRS) captured through an interactive voice response system (IVRS). The participant described the chronic low back pain (CLBP) during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain). Baseline value was calculated as mean of the scores over 5 days prior to randomization (initial pain assessment period). Post-baseline value was calculated as mean of the scores over the 7-day period prior to and including the post-baseline visit.

Daily average back pain was assessed on an 11-point numeric rating scale (NRS) captured through an interactive voice response system (IVRS). The participant described the chronic low back pain (CLBP) during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain). Baseline value was calculated as mean of the scores over 5 days prior to randomization (initial pain assessment period). Post-baseline value was calculated as mean of the scores over the 7-day period prior to and including the post-baseline visit. Participants with specified reduction (as percent) from baseline at Week 16 are reported.

Daily average back pain was assessed on an 11-point numeric rating scale (NRS) captured through an interactive voice response system (IVRS). The participant described the chronic low back pain (CLBP) during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain). Baseline value was calculated as mean of the scores over 5 days prior to randomization (initial pain assessment period). Post-baseline value was calculated as mean of the scores over the 7-day period prior to and including the post-baseline visit.

BPI-sf: self-report questionnaire rated on an 11-point scale, consists of 5 questions to assess severity and impact of pain on daily functions. Question 1-4 (Q1-Q4) measure severity of pain (worst, least, average, right now), each question ranging between 0 (no pain) to 10 (pain as bad as you can imagine). Question 5 (Q5) consists of 7 items which measure level of interference of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life), each item ranging from 0 (does not interfere) to 10 (completely interferes). Results are reported for worst and average pain, each with a score range: 0 (no pain) and 10 (pain as bad as you can imagine), higher scores indicated worse pain.

BPI-sf: self-report questionnaire rated on an 11-point scale, consists of 5 questions to assess severity and impact of pain on daily functions. Question 1-4 (Q1-Q4) measure severity of pain (worst, least, average, right now), each question ranging between 0 (no pain) to 10 (pain as bad as you can imagine). Question 5 (Q5) consists of 7 items which measure pain interference (PI) on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life), each item ranging from 0 (does not interfere) to 10 (completely interferes); higher score = greater impairment. The 7 items in Q5 averaged to obtain pain interference index (function composite score), range: 0 (no interference) to 10 (complete interference); higher score = greater impairment.

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

Chronic Low Back Pain (CLBP) Responder Index: A response was defined as reduction of at least 30% in mean daily average LBPI from baseline to a specified week, decrease of at least 30% in PGA of low back pain from baseline to the specified week and no worsening (increase) in RMDQ total score from baseline to the specified week. Participants who were responders were reported.

WPAI:SHP is a self-administered questionnaire that measures the effect of general health and symptom severity on work productivity and regular activities. Four scores are derived as percent: activity impairment (AI), impairment while working (IW), overall work impairment (OWI), work time missed (WTM). Each of 4 scores expressed as impairment percentages with a total possible score range of 0 to 100, high percentage= more impairment, less productivity.

In case of inadequate pain relief for CLBP or for non-CLBP related pain, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication.

In case of inadequate pain relief for CLBP or for non-CLBP related pain, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication.

In case of inadequate pain relief for CLBP or for non-CLBP related pain, acetaminophen up to 3000 mg per day up to 3 days per week could be taken as rescue medication.

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.

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

Analysis was done by setting concentration values below the lower limit of quantification (LLOQ) to zero.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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 Week 24 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.