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

• ClinicalTrials.gov Identifier: NCT01087203
• Recruitment Status: Terminated
• First Posted: March 16, 2010
• Last Update Posted: August 30, 2012
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: March 11, 2010
• First Posted Date: March 16, 2010
• Last Update Posted Date: August 30, 2012
• Study Start Date: March 2010
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 12, 2010): Change from Baseline to Week 16 in the average Diabetic Peripheral Neuropathy (DPN) pain as measured by an 11-point Numeric Rating Scale (NRS) for tanezumab vs. placebo treatment. [ Time Frame: Baseline, Wk 16 ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT01087203 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: April 9, 2010)

• Change from Baseline to Weeks 1, 2, 4, 6, 8, and 12 in the average DPN pain NRS score derived from the patient daily diary. [ Time Frame: Baseline, Wks 2, 4, 6, 8 & 12 ]
• Cumulative distribution of percent change from Baseline in the average DPN pain NRS score to Week 16. [ Time Frame: Baseline & Wk 16 ]
• Response as defined by a ≥30%, ≥50%, ≥70% and a ≥90% reduction from Baseline in the average DPN pain NRS score derived from the patient daily diary at Weeks 1, 2, 4, 6, 8,12 and 16. [ Time Frame: Baseline, Wks 1, 2, 4, 6, 8, 12, & 16 ]
• Change from Baseline to Weeks 8 and 16 in the Brief Pain Inventory-short form (BPI-sf) scores. [ Time Frame: Baseline, Wks 8 & 16 ]
• Change from Baseline to Weeks 8 and 16 in the Neuropathic Pain Symptom Inventory (NPSI). [ Time Frame: Baseline, Wks 8 & 16 ]
• Change from Baseline to Weeks 4, 8, 12 and 16 in Patient's Global Assessment of Diabetic Peripheral Neuropathy. [ Time Frame: Baseline, Wks 8 & 16 ]
• Treatment Response: Improvement of ≥2 points in Patient's Global Assessment of Diabetic Peripheral Neuropathy at Weeks 4, 8, 12 and 16. [ Time Frame: Baseline, Wks 4, 8, 12 & 16 ]
• Change from Baseline to Week 16 in the EuroQol (EQ-5D) Health Questionnaire. [ Time Frame: Baseline & Wk 16 ]
• Time to discontinuation due to lack of efficacy. [ Time Frame: Time to discontinuation ]
• Usage of Rescue Medication. [ Time Frame: Wks 1, 2, 4, 6, 8, 12, & 16 ]
• Adverse events. [ Time Frame: Baseline, Wks 2, 4, 6, 8, 12, 16 & 24 ]
• Safety laboratory testing (chemistry, hematology, urinalysis). [ Time Frame: Baseline, Wks 4, 8, 16, & 24 ]
• Single Electrocardiogram (ECG) 12-lead. [ Time Frame: Baseline, Wks 2, 4, 6, 8, 12, 16, & 24 ]
• Physical examinations. [ Time Frame: Wks 16 & 24 ]
• Vital signs. [ Time Frame: Baseline, Wks 2, 4, 6, 8, 12, 16 & 24 ]
• Anti drug antibody (ADA): serum samples collected predose on Day 1 (Baseline), predose at Week 8 (trough sample), Weeks 16 and 24 for assessment of immunogenicity. [ Time Frame: Baseline, Wks 8, 16 & 24 ]
• Neurological exam. [ Time Frame: Baseline, Wks 2, 4, 6, 8, 12, 16 & 24 ]
• Change in the Neuropathy Symptoms and Change (NSC) score from Baseline to Week 16. [ Time Frame: Baseline & Wk 16 ]
• Change in Quantitative Sensory Testing (QST) in leg from Baseline to Week 16. [ Time Frame: Baseline & Wk 16 ]
• Change in density of nerve fibers in the leg from Baseline to Week 16. [ Time Frame: Baseline & Wk 16 ]
• Plasma tanezumab samples predose on Day 1 (Baseline), Weeks 2, 4, predose at Week 8 (trough sample), Weeks 12, 16 and 24 to characterize tanezumab pharmacokinetics in patients with DPN. [ Time Frame: Baseline, Wks 2, 4, 8, 12, 16 & 24 ]
• Serum nerve growth factor (NGF) samples predose on Day 1 Baseline), predose at Week 8 (trough sample), Weeks 16 and 24 for pharmacodynamic analysis. [ Time Frame: Baseline, Wks 8, 16, & 24 ]

Original Secondary Outcome Measures (submitted: March 12, 2010)

• Change from Baseline to Weeks 1, 2, 4, 6, 8, and 12 in the average DPN pain NRS score derived from the patient daily diary. [ Time Frame: Baseline, Wks 2, 4, 6, 8 & 12 ]
• Cumulative distribution of percent change from Baseline in the average DPN pain NRS score to Week 16. [ Time Frame: Baseline & Wk 16 ]
• Response as defined by a ≥30%, ≥50%, ≥70% and a ≥90% reduction from Baseline in the average DPN pain NRS score derived from the patient daily diary at Weeks 1, 2, 4, 6, 8,12 and 16. [ Time Frame: Baseline, Wks 1, 2, 4, 6, 8, 12, & 16 ]
• Change from Baseline to Weeks 8 and 16 in the Brief Pain Inventory-short form (BPI-sf) scores. [ Time Frame: Baseline, Wks 8 & 16 ]
• Change from Baseline to Weeks 8 and 16 in the Neuropathic Pain Symptom Inventory (NPSI). [ Time Frame: Baseline, Wks 8 & 16 ]
• Change from Baseline to Weeks 4, 8, 12 and 16 in Patient's Global Assessment of Diabetic Peripheral Neuropathy. [ Time Frame: Baseline, Wks 8 & 16 ]
• Treatment Response: Improvement of ≥2 points in Patient's Global Assessment of Diabetic Peripheral Neuropathy at Weeks 4, 8, 12 and 16. [ Time Frame: Baseline, Wks 4, 8, 12 & 16 ]
• Change from Baseline to Week 16 in the EuroQol (EQ-5D) Health Questionnaire. [ Time Frame: Baseline & Wk 16 ]
• Time to discontinuation due to lack of efficacy.
• Usage of Rescue Medication. [ Time Frame: Wks 1, 2, 4, 6, 8, 12, & 16 ]
• Adverse events. [ Time Frame: Baseline, Wks 2, 4, 6, 8, 12, 16 & 24 ]
• Safety laboratory testing (chemistry, hematology, urinalysis). [ Time Frame: Baseline, Wks 4, 8, 16, & 24 ]
• Single Electrocardiogram (ECG) 12-lead. [ Time Frame: Baseline, Wks 2, 4, 6, 8, 12, 16, & 24 ]
• Physical examinations. [ Time Frame: Wks 16 & 24 ]
• Vital signs. [ Time Frame: Baseline, Wks 2, 4, 6, 8, 12, 16 & 24 ]
• Anti drug antibody (ADA): serum samples collected predose on Day 1 (Baseline), predose at Week 8 (trough sample), Weeks 16 and 24 for assessment of immunogenicity. [ Time Frame: Baseline, Wks 8, 16 & 24 ]
• Neurological exam. [ Time Frame: Baseline, Wks 2, 4, 6, 8, 12, 16 & 24 ]
• Change in the Neuropathy Symptoms and Change (NSC) score from Baseline to Week 16. [ Time Frame: Baseline & Wk 16 ]
• Change in Quantitative Sensory Testing (QST) in leg from Baseline to Week 16. [ Time Frame: Baseline & Wk 16 ]
• Change in density of nerve fibers in the leg from Baseline to Week 16. [ Time Frame: Baseline & Wk 16 ]
• Plasma tanezumab samples predose on Day 1 (Baseline), Weeks 2, 4, predose at Week 8 (trough sample), Weeks 12, 16 and 24 to characterize tanezumab pharmacokinetics in patients with DPN. [ Time Frame: Baseline, Wks 2, 4, 8, 12, 16 & 24 ]
• Serum nerve growth factor (NGF) samples predose on Day 1 Baseline), predose at Week 8 (trough sample), Weeks 16 and 24 for pharmacodynamic analysis. [ Time Frame: Baseline, Wks 8, 16, & 24 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Of The Analgesic (Pain-Relief) Effects Of Tanezumab In Adult Patients With Diabetic Peripheral Neuropathy
• Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel Group, Proof Of Concept Study Of The Analgesic Effects Of Tanezumab In Adult Patients With Diabetic Peripheral Neuropathy
• Brief Summary: The purpose of this study is to determine the effectiveness and safety of the investigational drug, tanezumab, in adult patients with painful diabetic peripheral neuropathy.
• Detailed Description: This study was terminated on 18 November 2010 following a US FDA clinical hold for the tanezumab diabetic peripheral neuropathy clinical study which halted dosing and enrollment of patients on 19 July 2010 for potential safety issues.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Diabetic Peripheral Neuropathy

Intervention

• Biological: Tanezumab
  20 mg subcutaneous injection every 8 weeks x 2 doses (at Baseline and week 8)
  Other Name: PF-04383119
• Biological: placebo
  Placebo to match tanezumab 20 mg subcutaneous injection every 8 weeks x 2 doses (at Baseline and week 8)

Study Arms

• Experimental: Tanezumab
  Intervention: Biological: Tanezumab
• Placebo Comparator: Placebo
  Intervention: Biological: placebo

• Publications *: Bramson C, Herrmann DN, Carey W, Keller D, Brown MT, West CR, Verburg KM, Dyck PJ. Exploring the role of tanezumab as a novel treatment for the relief of neuropathic pain. Pain Med. 2015 Jun;16(6):1163-76. doi: 10.1111/pme.12677. Epub 2015 Jan 16.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 23, 2012): 73
• Original Estimated Enrollment (submitted: March 12, 2010): 160
• Actual Study Completion Date: November 2010
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of diabetes mellitus (high blood sugar) with HbA1c levels of ≤11% at Screening, and on a stable anti-diabetic medication regimen for the 30 days prior to randomization.
• Diagnosis of diabetic peripheral neuropathy pain in the legs or feet with decreased sensation in the feet or decreased/absent ankle jerk/ reflexes.
• Presence of ongoing pain due to diabetic peripheral neuropathy for at least 3 months.
• A pain score of greater than or equal to (≥) 4 for from diabetic peripheral neuropathy on the Numerical Rating Scale (NRS), a 11-point scale with 0 meaning no pain and 10 meaning worst pain at Screening.
• Be willing to stop all pain medications for diabetic peripheral neuropathy except for the limited use of acetaminophen (Tylenol) or ibuprofen-like (Motrin) medications between Screening and Baseline and not use prohibited pain medications throughout the duration of the study except as permitted by the study guidelines.

Exclusion Criteria:

• Painful neuropathies other than diabetic peripheral neuropathy.
• Other types of diabetic neuropathies.
• Patients with a past history of carpal tunnel syndrome (CTS) with signs or symptoms of CTS in the one year prior to Screening are not eligible for participation.
• Patients with fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to severe pain.
• Patients with a present (current) history of sciatica are not eligible for participation.
• The presence of pain conditions that cannot be distinguished from diabetic peripheral neuropathy such as peripheral vascular disease.
• Amputations dues to diabetes.
• Patient with any clinically significant medical condition or laboratory abnormalities.
• History, diagnosis, or signs and symptoms of clinically significant neurological diseases (such as Alzheimer's disease, head trauma, epilepsy or stroke).
• History, diagnosis, or signs and symptoms of clinically significant psychiatric diseases (such as bipolar disorder or schizophrenia).
• History of known alcohol, analgesic or drug abuse within 2 years of Screening.
• Pregnant women, lactating mothers, women suspected of being pregnant, and women who wish to be pregnant during the course of clinical study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States
• Removed Location Countries: Puerto Rico

Administrative Information

• NCT Number: NCT01087203
• Other Study ID Numbers: A4091031
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: August 2012