Trial Outcomes & Findings for A Study Of The Analgesic (Pain-Relief) Effects Of Tanezumab In Adult Patients With Diabetic Peripheral Neuropathy (NCT NCT01087203)

Last Updated: 2021-02-24

Results Overview

Participants assessed their DPN pain during the past 24 hours using 11-point Numeric Rating Scale (NRS) with score range of 0 (no pain) to 10 ( worst possible pain). Baseline score was calculated as the mean of the average pain scores over the 3 days in the initial pain assessment period. The Week 16 value was the average DPN Pain score calculated for the 7 days prior to and including Day 113 (Week 16).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

73 participants

Primary outcome timeframe

Baseline, Week 16

Results posted on

2021-02-24

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Overall Study STARTED	35	38
Overall Study COMPLETED	3	3
Overall Study NOT COMPLETED	32	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	2	6
Overall Study Lack of Efficacy	1	2
Overall Study Study terminated by sponsor	27	27

Baseline Characteristics

A Study Of The Analgesic (Pain-Relief) Effects Of Tanezumab In Adult Patients With Diabetic Peripheral Neuropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.	Total n=73 Participants Total of all reporting groups
Age, Continuous	59.6 Years STANDARD_DEVIATION 11.6 • n=5 Participants	61.6 Years STANDARD_DEVIATION 8.9 • n=7 Participants	60.7 Years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	27 Participants n=7 Participants	47 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. Last Observation Carried Forward (LOCF) method of imputation was used.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Change From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 Baseline	6.91 Units on a scale Standard Deviation 1.50	6.59 Units on a scale Standard Deviation 1.40
Change From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 Change at Week 16	-1.04 Units on a scale Standard Deviation 1.92	-2.10 Units on a scale Standard Deviation 3.14

SECONDARY outcome

Timeframe: Baseline, Week 1, 2, 4, 6, 8, 12

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. LOCF method of imputation was used.

Participant rated their DPN pain using 11-point NRS with score ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicated greater level of pain. Change: score at observation minus score at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Change From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 1, 2, 4, 6, 8, and 12 Baseline	6.91 Units on a scale Standard Deviation 1.50	6.59 Units on a scale Standard Deviation 1.40
Change From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 1, 2, 4, 6, 8, and 12 Change at Week 1	-0.76 Units on a scale Standard Deviation 1.31	-0.97 Units on a scale Standard Deviation 1.50
Change From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 1, 2, 4, 6, 8, and 12 Change at Week 2	-1.00 Units on a scale Standard Deviation 1.67	-1.31 Units on a scale Standard Deviation 1.92
Change From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 1, 2, 4, 6, 8, and 12 Change at Week 4	-0.95 Units on a scale Standard Deviation 1.75	-1.78 Units on a scale Standard Deviation 2.55
Change From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 1, 2, 4, 6, 8, and 12 Change at Week 6	-0.95 Units on a scale Standard Deviation 1.68	-2.04 Units on a scale Standard Deviation 2.86
Change From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 1, 2, 4, 6, 8, and 12 Change at Week 8	-0.98 Units on a scale Standard Deviation 1.83	-2.16 Units on a scale Standard Deviation 2.96
Change From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 1, 2, 4, 6, 8, and 12 Change at Week 12	-1.00 Units on a scale Standard Deviation 1.89	-2.14 Units on a scale Standard Deviation 3.12

SECONDARY outcome

Timeframe: Week 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. LOCF method of imputation was used.

Participant rated their DPN pain using 11-point NRS with score ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicated greater level of pain.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Number of Participants With Cumulative Reduction From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 Greater than (>) 0%	23 Participants	24 Participants
Number of Participants With Cumulative Reduction From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 Greater than equal to (>=) 10%	18 Participants	20 Participants
Number of Participants With Cumulative Reduction From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 >= 20%	10 Participants	20 Participants
Number of Participants With Cumulative Reduction From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 >= 30%	7 Participants	15 Participants
Number of Participants With Cumulative Reduction From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 >= 40%	5 Participants	14 Participants
Number of Participants With Cumulative Reduction From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 >= 50%	5 Participants	12 Participants
Number of Participants With Cumulative Reduction From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 >= 60%	3 Participants	11 Participants
Number of Participants With Cumulative Reduction From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 >= 70%	2 Participants	11 Participants
Number of Participants With Cumulative Reduction From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 >= 80%	1 Participants	9 Participants
Number of Participants With Cumulative Reduction From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 >= 90%	1 Participants	4 Participants
Number of Participants With Cumulative Reduction From Baseline in Average Diabetic Peripheral Neuropathy (DPN) Pain Score at Week 16 = 100%	1 Participants	4 Participants

SECONDARY outcome

Timeframe: Week 1, 2, 4, 6, 8, 12, 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. LOCF method of imputation was used.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 1: >= 30% Reduction	4 Participants	8 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 1: >= 50% Reduction	2 Participants	3 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 1: >= 70% Reduction	0 Participants	1 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 1: >= 90% Reduction	0 Participants	0 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 2: >= 30% Reduction	6 Participants	12 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 2: >= 50% Reduction	3 Participants	7 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 2: >= 70% Reduction	2 Participants	1 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 2: >= 90% Reduction	1 Participants	0 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 4: >= 30% Reduction	6 Participants	15 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 4: >= 50% Reduction	3 Participants	9 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 4: >= 70% Reduction	2 Participants	5 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 4: >= 90% Reduction	1 Participants	1 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 6: >= 30% Reduction	6 Participants	15 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 6: >= 50% Reduction	2 Participants	10 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 6: >= 70% Reduction	2 Participants	7 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 6: >= 90% Reduction	1 Participants	3 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 8: >= 30% Reduction	6 Participants	15 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 8: >= 50% Reduction	4 Participants	12 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 8: >= 70% Reduction	2 Participants	8 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 8: >= 90% Reduction	1 Participants	5 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 12: >= 30% Reduction	7 Participants	15 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 12: >= 50% Reduction	4 Participants	12 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 12: >= 70% Reduction	2 Participants	11 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 12: >= 90% Reduction	1 Participants	4 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 16: >= 30% Reduction	7 Participants	15 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 16: >= 50% Reduction	5 Participants	12 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 16: >= 70% Reduction	2 Participants	11 Participants
Number of Participants With at Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average DPN Pain Score: Last Observation Carried Forward (LOCF) Week 16: >= 90% Reduction	1 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline, Week 8, 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. LOCF method of imputation was used. Here, Overall Number of Participants Analyzed signifies participants evaluable for this measure.

BPI-sf (Brief Pain Inventory-short form) is a participant-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the 24-hour period prior to evaluation. It consists of 5 questions. Questions 1-4 measure the magnitude of pain at its worst and least (in the last 24 hours), average, and right now. Responses are provided by the participant on an 11-point numeric rating scale with anchors at 0 (No Pain) and 10 (Pain as bad as you can imagine). Question 5 consists of 7 item subsets (A to G) which measure the level of interference of pain on daily functions. Responses are given on an 11-point numeric rating scale with anchors at 0 (Does not interfere) and 10 (Completely interferes). The instrument is scored by item and by dimension, with lower scores indicating less pain or pain interference.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=37 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Worst and Average Pain Score at Week 8 and 16 Worst Pain: Baseline	7.33 Units on a scale Standard Deviation 1.24	6.92 Units on a scale Standard Deviation 1.38
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Worst and Average Pain Score at Week 8 and 16 Worst Pain: Change at Week 8	-1.13 Units on a scale Standard Deviation 1.70	-2.38 Units on a scale Standard Deviation 3.06
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Worst and Average Pain Score at Week 8 and 16 Worst Pain: Change at Week 16	-1.10 Units on a scale Standard Deviation 1.65	-2.32 Units on a scale Standard Deviation 3.06
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Worst and Average Pain Score at Week 8 and 16 Average Pain: Baseline	6.17 Units on a scale Standard Deviation 1.21	5.62 Units on a scale Standard Deviation 1.40
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Worst and Average Pain Score at Week 8 and 16 Average Pain: Change at Week 8	-0.77 Units on a scale Standard Deviation 1.43	-1.65 Units on a scale Standard Deviation 2.14
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Worst and Average Pain Score at Week 8 and 16 Average Pain: Change at Week 16	-0.73 Units on a scale Standard Deviation 1.36	-1.59 Units on a scale Standard Deviation 2.15

SECONDARY outcome

Timeframe: Baseline, Week 8, 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. Here, 'Overall Number of Participants Analyzed'= participants evaluable for this measure. 'Number Analyzed' = participants who were evaluable for this measure at given time point for each arm, respectively. LOCF method of imputation was used.

Participant rated questionnaire to evaluate different symptoms of neuropathic pain (burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]) during past 24-hour period and included 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generated a score in each of the relevant dimensions and a total score of 0-100. Higher score indicated a greater intensity of pain.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=36 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score at Week 8 and 16: Last Observation Carried Forward (LOCF) Baseline	0.50 Units on a scale Standard Deviation 0.21	0.45 Units on a scale Standard Deviation 0.18
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score at Week 8 and 16: Last Observation Carried Forward (LOCF) Change at Week 8	-0.15 Units on a scale Standard Deviation 0.21	-0.20 Units on a scale Standard Deviation 0.21
Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score at Week 8 and 16: Last Observation Carried Forward (LOCF) Change at Week 16	-0.13 Units on a scale Standard Deviation 0.18	-0.17 Units on a scale Standard Deviation 0.22

SECONDARY outcome

Timeframe: Baseline, Week 8, 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. Here, 'Overall Number of Participants Analyzed= participants evaluable for this measure. 'Number Analyzed' =participants who were evaluable for this measure at given time point for each arm, respectively.

BPI-sf (Brief Pain Inventory-short form) is a participant-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the 24-hour period prior to evaluation. It consisted of 5 questions. Questions 1-4 measure the magnitude of pain at its worst and least (in the last 24 hours), average, and right now. Responses were provided by the participant on an 11-point numeric rating scale with anchors at 0 (No Pain) and 10 (Pain as bad as you can imagine). Question 5 consisted of 7 item subsets (A to G) as being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point numeric rating scale with anchors at 0 (Does not interfere) and 10 (Completely interferes). The instrument was scored by item and by dimension, with lower scores indicated less pain or pain interference.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=37 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 Pain Interference Index (PII);Baseline	5.23 Units on scale Standard Deviation 2.36	4.71 Units on scale Standard Deviation 2.41
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PII: Change at Week 8	-1.12 Units on scale Standard Deviation 2.32	-1.75 Units on scale Standard Deviation 3.15
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PII: Change at Week 16	-1.64 Units on scale Standard Deviation 0.51	-1.24 Units on scale Standard Deviation 2.18
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI General Activity: Baseline	5.30 Units on scale Standard Deviation 2.23	4.49 Units on scale Standard Deviation 3.02
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI General Activity: Change at Week 8	-1.26 Units on scale Standard Deviation 2.20	-1.81 Units on scale Standard Deviation 3.86
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI General Activity: Change at Week 16	-2.00 Units on scale Standard Deviation 0.00	-1.33 Units on scale Standard Deviation 3.51
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI Walking Ability: Baseline	5.43 Units on scale Standard Deviation 2.50	5.54 Units on scale Standard Deviation 2.80
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI Walking Ability: Change at Week 8	-1.09 Units on scale Standard Deviation 3.18	-2.25 Units on scale Standard Deviation 3.21
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI Walking Ability: Change at Week 16	-2.00 Units on scale Standard Deviation 1.41	-2.33 Units on scale Standard Deviation 2.52
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI Sleep: Baseline	5.70 Units on scale Standard Deviation 2.78	5.95 Units on scale Standard Deviation 2.59
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI Sleep: Change at Week 8	-0.87 Units on scale Standard Deviation 2.69	-2.34 Units on scale Standard Deviation 3.60
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI Sleep: Change at Week 16	-1.00 Units on scale Standard Deviation 0.00	-2.00 Units on scale Standard Deviation 1.00
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI Normal Work: Baseline	5.33 Units on scale Standard Deviation 2.59	4.78 Units on scale Standard Deviation 2.89
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI Normal Work: Change at Week 8	-1.04 Units on scale Standard Deviation 2.53	-1.44 Units on scale Standard Deviation 3.86
Change From Baseline in BPI-sf Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and Week 16 PI Normal Work: Change at Week 16	-1.50 Units on scale Standard Deviation 0.71	-0.67 Units on scale Standard Deviation 3.51

SECONDARY outcome

Timeframe: Baseline, Week 4, 8, 12, 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. Here, 'Overall Number Analyzed' signifies those participants who were evaluable for this measure. LOCF method of imputation was used.

The PGA is a global evaluation that utilizes a 5-point Likert scale with a score of 1 being the best (very good: Asymptomatic and no limitation of normal activities) and a score of 5 being the worst (very poor: Very severe symptoms which are intolerable and inability to carry out all normal activities).

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=37 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Change From Baseline in Patient's Global Assessment (PGA) of Diabetic Peripheral Neuropathy (DPN) at Week 4, 8, 12 and 16 Baseline	3.17 Units on a scale Standard Deviation 0.65	2.89 Units on a scale Standard Deviation 0.61
Change From Baseline in Patient's Global Assessment (PGA) of Diabetic Peripheral Neuropathy (DPN) at Week 4, 8, 12 and 16 Change at Week 4	-0.47 Units on a scale Standard Deviation 0.86	-0.54 Units on a scale Standard Deviation 0.84
Change From Baseline in Patient's Global Assessment (PGA) of Diabetic Peripheral Neuropathy (DPN) at Week 4, 8, 12 and 16 Change at Week 8	-0.63 Units on a scale Standard Deviation 0.76	-0.57 Units on a scale Standard Deviation 0.93
Change From Baseline in Patient's Global Assessment (PGA) of Diabetic Peripheral Neuropathy (DPN) at Week 4, 8, 12 and 16 Change at Week 12	-0.63 Units on a scale Standard Deviation 0.76	-0.62 Units on a scale Standard Deviation 0.89
Change From Baseline in Patient's Global Assessment (PGA) of Diabetic Peripheral Neuropathy (DPN) at Week 4, 8, 12 and 16 Change at Week 16	-0.63 Units on a scale Standard Deviation 0.76	-0.59 Units on a scale Standard Deviation 0.90

SECONDARY outcome

Timeframe: Week 4, 8, 12, 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. LOCF method of imputation was used.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Number of Participants With Improvement of at Least 2 Points in Patient's Global Assessment (PGA) of Diabetic Peripheral Neuropathy Week 16	2 Participants	5 Participants
Number of Participants With Improvement of at Least 2 Points in Patient's Global Assessment (PGA) of Diabetic Peripheral Neuropathy Week 4	1 Participants	6 Participants
Number of Participants With Improvement of at Least 2 Points in Patient's Global Assessment (PGA) of Diabetic Peripheral Neuropathy Week 8	2 Participants	5 Participants
Number of Participants With Improvement of at Least 2 Points in Patient's Global Assessment (PGA) of Diabetic Peripheral Neuropathy Week 12	2 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. 'Overall Number of Participants Analyzed'=participants evaluable for this measure. Here, 'Number Analyzed' signifies those participants who were evaluable for this measure at given time point for each 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: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression; 1 indicates better health state (no problems); 3 indicates worst health state (extreme problems). Scoring formula developed by Euro Quality of life 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 indicated a better health state.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=37 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Change From Baseline in Euro Quality of Life (EQ-5D)- Health State Profile Utility at Week 16 Baseline	0.54 Units on a scale Standard Deviation 0.29	0.62 Units on a scale Standard Deviation 0.22
Change From Baseline in Euro Quality of Life (EQ-5D)- Health State Profile Utility at Week 16 Change at Week 16	0.00 Units on a scale Standard Deviation 0.05	-0.06 Units on a scale Standard Deviation 0.11

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Time to Discontinuation Due to Lack of Efficacy	5.0 Days Interval 5.0 to 5.0	21.0 Days Interval 20.0 to 22.0

SECONDARY outcome

Timeframe: Week 1, 2, 4, 6, 8, 12, 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. LOCF method of imputation was used. 'Overall Number of Participants Analyzed'=participants evaluable for this measure. Here, 'Number Analyzed' signifies those participants who were evaluable for this measure at given time point for each arm, respectively.

Participants who did not experience adequate pain relief for DPN pain during the treatment period took acetaminophen 3000 mg/day up to 3 days/week as rescue medication.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=28 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Number of Participants Who Used Rescue Medication Week 1	14 Participants	20 Participants
Number of Participants Who Used Rescue Medication Week 2	13 Participants	17 Participants
Number of Participants Who Used Rescue Medication Week 4	12 Participants	13 Participants
Number of Participants Who Used Rescue Medication Week 6	13 Participants	13 Participants
Number of Participants Who Used Rescue Medication Week 8	12 Participants	12 Participants
Number of Participants Who Used Rescue Medication Week 12	12 Participants	12 Participants
Number of Participants Who Used Rescue Medication Week 16	12 Participants	12 Participants

SECONDARY outcome

Timeframe: Week 1, 2, 4, 6, 8, 12, 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. LOCF method of imputation was used. Here, 'Overall Number of Participants Analyzed'=participants evaluable for this measure. 'Number Analyzed' signifies those participants who were evaluable for this measure at given time point for each arm, respectively.

Participants who did not experience adequate pain relief for DPN pain during the treatment period took acetaminophen 3000 mg/day up to 3 days/week as rescue medication.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=28 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Days Per Week of Rescue Medication Usage Week 2	1 Days per week Interval 0.0 to 7.0	1 Days per week Interval 0.0 to 7.0
Days Per Week of Rescue Medication Usage Week 4	1 Days per week Interval 0.0 to 7.0	0 Days per week Interval 0.0 to 7.0
Days Per Week of Rescue Medication Usage Week 8	1 Days per week Interval 0.0 to 7.0	0 Days per week Interval 0.0 to 5.0
Days Per Week of Rescue Medication Usage Week 12	1 Days per week Interval 0.0 to 7.0	0 Days per week Interval 0.0 to 5.0
Days Per Week of Rescue Medication Usage Week 16	1 Days per week Interval 0.0 to 7.0	0 Days per week Interval 0.0 to 5.0

SECONDARY outcome

Timeframe: Week 1, 2, 4, 6, 8, 12, 16

Participants who did not experience adequate pain relief for DPN pain during the treatment period took acetaminophen 3000 mg/day up to 3 days/week as rescue medication.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=28 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Amount of Rescue Medication Taken Week 1	2666.67 mg/week Standard Deviation 4090.46	2759.26 mg/week Standard Deviation 3716.83
Amount of Rescue Medication Taken Week 2	2020.83 mg/week Standard Deviation 2939.53	2178.57 mg/week Standard Deviation 3174.59
Amount of Rescue Medication Taken Week 4	1354.17 mg/week Standard Deviation 1997.17	1464.29 mg/week Standard Deviation 2567.35
Amount of Rescue Medication Taken Week 6	1395.83 mg/week Standard Deviation 1978.03	1250.00 mg/week Standard Deviation 2420.97
Amount of Rescue Medication Taken Week 8	1354.17 mg/week Standard Deviation 1997.17	1160.71 mg/week Standard Deviation 2419.27
Amount of Rescue Medication Taken Week 12	1416.67 mg/week Standard Deviation 2009.04	1160.71 mg/week Standard Deviation 2419.27
Amount of Rescue Medication Taken Week 16	1416.67 mg/week Standard Deviation 2009.04	1160.71 mg/week Standard Deviation 2419.27

SECONDARY outcome

Timeframe: Baseline up to 112 days after last dose of study treatment (up to 169 days)

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication.

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 112 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	19 Participants	24 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. Here, 'Overall Number of Participants Analyzed'= total number of participants with at least one observation of the given laboratory test while on study treatment or during lag time.

Criteria:Hemoglobin(Hgb),hematocrit,red blood cell(RBC)count:less than(\<)0.8\*lower limit of normal(LLN), mean cell Hgb,mean corpuscular volume,mean corpuscular Hgb concentration,mean platelet volume:\<0.9\*LLNor\>1.1\*upper limit of normal(ULN),platelet:\<0.5\*LLN \>1.75\* ULN, lymphocyte,neutrophil:\<0.8\*LLN or\>1.2\*ULN,basophil, eosinophil,monocyte:\>1.2\*ULN;bilirubin(total, direct,)\>1.5\*ULN, aspartate and alanine aminotransferase,alkaline phosphatase:\> 3.0\*ULN;gamma GT\>3.0;cholestrol,triglycerides:\>1.3\*ULN; total protein, albumin:\<0.8\*LLN or\>1.2\*ULN ;blood urea nitrogen,creatinine:\>1.3\*ULN,uric acid\>1.2\*ULN;sodium \<0.95\*LLNor\>1.05\*ULN,potassium,chloride,calcium,bicarbonate, magnesium:\<0.9\*LLN or \>1.1\*ULN;phosphate\<0.8\*LLN or\>1.2\*ULN;glucose \<0.6\*LLNor\>1.5\*ULN,glycosylated Hgb\>1.3\*ULN,creatine kinase \>2.0\*ULN;urine(specific gravity\<1.003or\>1.030;pH \<4.8or\>8;glucose,ketone,proteins,blood/Hgb,bilirubin,nitrite\>=1;WBC, RBC≥20/HPF;hyaline cast≥1;epithelial cell\>=6;bacteria \>1);serum pregnancy \>=1.

Outcome measures

Outcome measures
Measure	Placebo n=34 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=36 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Number of Participants With Clinically Significant Laboratory Values	33 Participants	32 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication.

Following parameters were analyzed for ECG abnormality: PR interval, QRS interval, QT interval, QT interval corrected using the Fridericia's formula (QTcF), QT interval corrected using the Bazett's formula (QTcB), RR interval and heart rate (HR). Number of participants with clinically significant abnormal ECG findings reported as adverse events were presented.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities	1 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication.

Physical examination included examination of following sites in addition to general examination: abdomen, ears, extremities, eyes, head, heart, musculoskeletal, neck, nose, skin, throat, lungs and thyroid.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Number of Participants With Clinically Significant Change From Baseline Physical Examination	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication.

Following parameters were analyzed for examination of vital signs: body temperature, blood pressure, pulse rate and respiratory rate. Number of participants with clinically significant abnormality in vital signs reported as adverse events were presented.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Number of Participants With Clinically Significant Vital Signs Abnormalities	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 8, 16, 24

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. Here, 'Number Analyzed' signifies those participants who were evaluable for this measure at given time points for Tanezumab 20 mg group.

Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Number of Participants With Anti Drug Antibody (ADA) for Tanezumab Baseline	0 Participants	—
Number of Participants With Anti Drug Antibody (ADA) for Tanezumab Week 8	0 Participants	—
Number of Participants With Anti Drug Antibody (ADA) for Tanezumab Week 16	1 Participants	—
Number of Participants With Anti Drug Antibody (ADA) for Tanezumab Week 24	0 Participants	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12, 16 and 24

Neurologic examination assessed strength of groups of muscles of the head and neck, upper limbs and lower limbs, deep tendon reflexes and sensation (tactile, vibration, joint position sense and pin prick) of index fingers and great toes in order to complete the NIS. The NIS consists of 74 items (37 items assessed on the right side and 37 items assessed on the left side). Each item was rated on a scale of either 0 to 4 or 0 to 2 points, which were summed to calculate a total score. The NIS total score ranges from 0 to 244, where higher scores represent greater impairment.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=37 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16 and 24: Last Observation Carried Forward (LOCF) Baseline	16.42 Units on a scale Standard Deviation 10.42	15.86 Units on a scale Standard Deviation 10.77
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16 and 24: Last Observation Carried Forward (LOCF) Change at Week 2	-1.90 Units on a scale Standard Deviation 3.13	-1.40 Units on a scale Standard Deviation 4.93
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16 and 24: Last Observation Carried Forward (LOCF) Change at Week 4	-1.30 Units on a scale Standard Deviation 4.02	-0.35 Units on a scale Standard Deviation 7.12
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16 and 24: Last Observation Carried Forward (LOCF) Change at Week 8	-1.63 Units on a scale Standard Deviation 3.37	-0.24 Units on a scale Standard Deviation 5.40
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16 and 24: Last Observation Carried Forward (LOCF) Change at Week 12	-2.27 Units on a scale Standard Deviation 3.87	-1.19 Units on a scale Standard Deviation 6.13
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16 and 24: Last Observation Carried Forward (LOCF) Change at Week 16	-1.58 Units on a scale Standard Deviation 3.83	-0.51 Units on a scale Standard Deviation 6.31
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16 and 24: Last Observation Carried Forward (LOCF) Change at Week 24	-1.18 Units on a scale Standard Deviation 3.77	-0.51 Units on a scale Standard Deviation 6.31

SECONDARY outcome

Timeframe: Baseline, Week 16

The NSC (Neuropathy symptoms and change) is a standardized instrument and has been used to evaluate participants for number of symptoms of peripheral neuropathy. The NSC score included 38 (muscle weakness, Q1-19; sensation, Q20-29; and autonomic symptoms, Q30-38) symptom questions where the participants indicated experiencing the number of symptoms (to any severity). The score ranged from 0 to 38, with higher scores indicated more symptoms. The change score is the participant's comparison of the symptoms at last evaluation to the symptoms at onset. A change from baseline \> 0 indicated increased neuropathy.

Outcome measures

Outcome measures
Measure	Placebo n=31 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=37 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Change From Baseline Neuropathy Symptoms and Change (NSC) Score at Week 16: Last Observation Carried Forward (LOCF) Baseline	6.97 Units on a scale Standard Deviation 4.04	7.57 Units on a scale Standard Deviation 3.49
Change From Baseline Neuropathy Symptoms and Change (NSC) Score at Week 16: Last Observation Carried Forward (LOCF) Change at Week 16	-1.07 Units on a scale Standard Deviation 1.84	-1.56 Units on a scale Standard Deviation 2.85

SECONDARY outcome

Timeframe: Baseline, Week 16

QST was performed on dorsum of foot and anterior thigh (at midpoint of a line from inguinal crease to midpoint of patella) to assess and quantify sensory function in lower extremity. Parameters were selected to assess small fiber function such as cooling detection threshold (mainly small diameter myelinated fibers, A delta), heat pain detection threshold (A delta and C fiber functions), and large fiber function via vibration detection threshold. normal deviate scores derived from a normal distribution of a reference population. A standard deviate score of 0 corresponds to 50th percentile of control population. Standard deviate score 1.96 corresponds to 95th percentile of normal distribution and -1.96 corresponds to 5th percentile of normal distribution. A normal deviate score indicated how many standard deviations higher (in case of positive normal deviate score) or lower (in case of negative normal deviate score) participant's value was relative to mean of reference population.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication. LOCF method of imputation was used.

IENF density was quantified in 3 millimeter (mm) immunostained skin punch biopsies containing epidermis and superficial dermis to evaluate the amount and morphological appearance of small diameter nerve fibers, both somatic and autonomic, in sensory neuropathies. IENF density was assessed from skin biopsies taken from the distal calves and distal thigh.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Change From Baseline in the Average Density of Protein Gene Product (PGP) 9.5-Positive Intraepidermal Nerve Fiber (IENF) at Week 16: LOCF Change at Week 16: Distal Calves	0.40 Fibers/mm Standard Error 0.22	-0.15 Fibers/mm Standard Error 0.21
Change From Baseline in the Average Density of Protein Gene Product (PGP) 9.5-Positive Intraepidermal Nerve Fiber (IENF) at Week 16: LOCF Change at Week 16: Distal Thighs	0.40 Fibers/mm Standard Error 0.45	-0.30 Fibers/mm Standard Error 0.45

SECONDARY outcome

Timeframe: Baseline(Day 1), Week 2, 4, 8, 12, 16, 24

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Plasma Tanezumab Concentration Day 1	13.66 nanogram per milliliter (ng/mL) Standard Deviation 59.710	—
Plasma Tanezumab Concentration Week 2	1752 nanogram per milliliter (ng/mL) Standard Deviation 610.54	—
Plasma Tanezumab Concentration Week 4	1316 nanogram per milliliter (ng/mL) Standard Deviation 438.16	—
Plasma Tanezumab Concentration Week 8	591.9 nanogram per milliliter (ng/mL) Standard Deviation 232.07	—
Plasma Tanezumab Concentration Week 12	475.9 nanogram per milliliter (ng/mL) Standard Deviation 430.22	—
Plasma Tanezumab Concentration Week 16	265.6 nanogram per milliliter (ng/mL) Standard Deviation 282.50	—
Plasma Tanezumab Concentration Week 24	97.77 nanogram per milliliter (ng/mL) Standard Deviation 59.975	—

SECONDARY outcome

Timeframe: Day 1, Week 8, 16, 24

Serum samples were analyzed for determining total NGF concentration. Total NGF was analyzed using a validated, sensitive and specific immunoaffinity enrichment liquid chromatography tandem mass spectrometric (IA/LC/MS/MS) method.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=37 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Serum Nerve Growth Factor (NGF) Day 1	48.10 picogram per milliliter (pg/mL) Standard Deviation 11.04	45.54 picogram per milliliter (pg/mL) Standard Deviation 12.25
Serum Nerve Growth Factor (NGF) Week 8	50.15 picogram per milliliter (pg/mL) Standard Deviation 11.21	4193.9 picogram per milliliter (pg/mL) Standard Deviation 1304
Serum Nerve Growth Factor (NGF) Week 16	46.12 picogram per milliliter (pg/mL) Standard Deviation 10.65	2811.3 picogram per milliliter (pg/mL) Standard Deviation 1284
Serum Nerve Growth Factor (NGF) Week 24	38.69 picogram per milliliter (pg/mL) Standard Deviation 4.47	2689.0 picogram per milliliter (pg/mL) Standard Deviation 316.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 up to Week 8

Population: ITT analysis set included all randomized participants who received at least 1 dose of study medication.

Number of participants are reported based on the maximum number of Subcutaneous doses of either tanezumab or placebo received.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Number of Participants With Subcutaneous Doses of Study Medication 1 dose	32 Participants	35 Participants
Number of Participants With Subcutaneous Doses of Study Medication 2 doses	3 Participants	3 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Tanezumab

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=35 participants at risk Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 participants at risk Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Cardiac disorders Carotid Artery Stenosis	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.6% 1/38 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=30 Participants Placebo matched to tanezumab (RN624 or PF-04383119) subcutaneous injection on Day 1 and Week 8.	Tanezumab n=38 Participants Tanezumab (RN624 or PF-04383119) 20 milligram (mg) subcutaneous injection on Day 1 and Week 8.
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Baseline: VDT Left Foot	1.64 Normal deviate score Standard Deviation 1.14	1.47 Normal deviate score Standard Deviation 1.22
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Baseline: CDT Left Foot	1.72 Normal deviate score Standard Deviation 0.87	1.54 Normal deviate score Standard Deviation 1.18
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Baseline: HPDT 0.5 Left Foot	0.07 Normal deviate score Standard Deviation 1.88	0.38 Normal deviate score Standard Deviation 2.21
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Baseline: HPDT 5.0 Left Foot	0.40 Normal deviate score Standard Deviation 2.23	1.06 Normal deviate score Standard Deviation 2.00
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Baseline: HPDT 5.0-0.5 Left Foot	0.64 Normal deviate score Standard Deviation 1.39	0.80 Normal deviate score Standard Deviation 1.38
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Baseline: VDT Left Thigh	1.31 Normal deviate score Standard Deviation 1.16	1.07 Normal deviate score Standard Deviation 1.28
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Baseline: CDT Left Thigh	1.52 Normal deviate score Standard Deviation 1.09	1.76 Normal deviate score Standard Deviation 1.05
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Baseline: HPDT 0.5 Left Thigh	-0.82 Normal deviate score Standard Deviation 1.50	-0.48 Normal deviate score Standard Deviation 1.17
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Baseline: HPDT 5.0 Left Thigh	-0.55 Normal deviate score Standard Deviation 1.70	-0.04 Normal deviate score Standard Deviation 1.41
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Baseline: HPDT 5.0-0.5 Left Thigh	0.71 Normal deviate score Standard Deviation 1.32	0.71 Normal deviate score Standard Deviation 1.42
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Change at Week 16: VDT Left Foot	-0.07 Normal deviate score Standard Deviation 0.66	-0.01 Normal deviate score Standard Deviation 0.90
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Change at Week 16: CDT Left Foot	0.02 Normal deviate score Standard Deviation 0.50	-0.16 Normal deviate score Standard Deviation 0.81
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Change at Week 16: HPDT 0.5 Left Foot	-0.27 Normal deviate score Standard Deviation 1.52	-0.04 Normal deviate score Standard Deviation 1.54
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Change at Week 16: HPDT 5.0 Left Foot	0.26 Normal deviate score Standard Deviation 1.53	0.09 Normal deviate score Standard Deviation 1.20
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Change at Week 16:HPDT 5.0-0.5 Left Foot	0.38 Normal deviate score Standard Deviation 1.27	0.21 Normal deviate score Standard Deviation 1.48
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Change at Week 16: VDT Left Thigh	-0.11 Normal deviate score Standard Deviation 0.88	-0.06 Normal deviate score Standard Deviation 0.87
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Change at Week 16: CDT Left Thigh	0.19 Normal deviate score Standard Deviation 0.95	0.09 Normal deviate score Standard Deviation 0.87
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Change at Week 16: HPDT 0.5 Left Thigh	-0.23 Normal deviate score Standard Deviation 1.36	-0.27 Normal deviate score Standard Deviation 1.40
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Change at Week 16: HPDT 5.0 Left	-0.11 Normal deviate score Standard Deviation 1.26	-0.05 Normal deviate score Standard Deviation 1.57
Change From Baseline in Quantitative Sensory Testing (QST) at Week 16 Change at Week 16:HPDT 5.0-0.5 Left Thigh	0.23 Normal deviate score Standard Deviation 1.57	0.22 Normal deviate score Standard Deviation 1.38