PF-06372865 In Subjects With Chronic Low Back Pain

A Randomized, Double Blind, Placebo- And Active-controlled, 4 Week, Multi-center, Parallel Group Study Assessing The Analgesic Effect, Safety And Tolerability Of Pf-06372865 In Subjects With Chronic Low Back Pain Using Naproxen As Positive Control

PF-06372865 In Subjects With Chronic Low Back Pain

Study Overview

• Status: Completed
• Conditions: Chronic Low Back Pain
• Intervention / Treatment: Drug: PF-06372865; Drug: Placebo; Drug: Naproxen

• Study Type: Interventional
• Enrollment (Actual): 302
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85202
      • Agave Clinical Research, LLC
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center, Inc.
  • California
    • Anaheim, California, United States, 92804
      • Global Research
    • Fresno, California, United States, 93710
      • Neuro-Pain Medical Center
    • North Hollywood, California, United States, 91606
      • Providence Clinical Research
    • Wildomar, California, United States, 92595
      • Elite Clinical Trials, Incorporate
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Fort Lauderdale, Florida, United States, 33306
      • S&W Clinical Research
    • Gainesville, Florida, United States, 32605
      • Florida Research Network, LLC
    • Hollywood, Florida, United States, 33024
      • Broward Research Group
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Pembroke Pines, Florida, United States, 33028
      • Pines Clinical Research Inc.
    • Port Orange, Florida, United States, 32129
      • Accord Clinical Research, LLC
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • South Miami, Florida, United States, 33143
      • Arthritis & Rheumatic Care Center
  • Georgia
    • Atlanta, Georgia, United States, 30344
      • Better Health Clinical Research, Inc.
    • Blue Ridge, Georgia, United States, 30513
      • River Birch Research Alliance, Llc
    • Columbus, Georgia, United States, 31904
      • Columbus Regional Research Institute
    • Columbus, Georgia, United States, 31901
      • Family medicine center
    • Marietta, Georgia, United States, 30060
      • Drug Studies America
    • Newnan, Georgia, United States, 30265
      • Better Health Clinical Research, Inc.
    • Newnan, Georgia, United States, 30265
      • Better Health Clinical Research, Inc./Georgia Pain & Spine Care, Inc.
    • Savannah, Georgia, United States, 31405
      • Southeast Regional Research Group
    • Woodstock, Georgia, United States, 30189
      • North Georgia Clinical Research
    • Woodstock, Georgia, United States, 30189
      • North Georgia Internal Medicine
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Chicago Anesthesia Associates
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Centex Studies, Inc
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research, Inc.
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • CRC of Jackson
    • Jackson, Mississippi, United States, 39202
      • Physician's Surgery Center
  • New York
    • Hartsdale, New York, United States, 10530
      • Drug Trials America
    • Rochester, New York, United States, 14618
      • AAIR Research Center
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Internal Medicine Consultants, Inc.
    • Winston-Salem, North Carolina, United States, 27103
      • The Center for Clinical Research
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network (Oregon), Inc.
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • Texas
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • San Antonio, Texas, United States, 78229
      • Progressive Clinical Research
    • San Antonio, Texas, United States, 78229
      • Lee Medical Associates, PA
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • National Clinical Research - Norfolk, Inc.
  • Washington
    • Seattle, Washington, United States, 98104
      • Summit Research Network (Seattle) Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

-

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-06372865; Daily BID dosing for 4 weeks	Drug: PF-06372865; Dose level 1 daily dosing BID for 1 week followed by dose level 2 daily BID for 3 weeks
Placebo Comparator: Placebo; Daily BID dosing for 4 weeks	Drug: Placebo; Placebo for PF-06372865 and placebo for naproxen daily
Active Comparator: Naproxen; Daily BID dosing for 4 weeks	Drug: Naproxen; 500 mg BID for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Daily Low Back Pain Intensity (LBPI) Score as Measured by an 11-point Numeric Rating Scale (NRS) at Week 4	Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicate higher pain. Baseline value was calculated as the mean of the scores over the last 7 days in the placebo run-in period, prior to randomization. Post-baseline weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week.	Baseline, Week 4
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. The 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 or incapacity, congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.	Baseline up to 28 days after the last dose of study treatment (Day 56)
Number of Participants With Laboratory Abnormalities	Abnormality criteria included: hemoglobin, hematocrit and red blood cells (RBCs) (less than [<] 0.8*lower limit of normal [LLN]); white blood cells (WBC) (<0.6*LLN, greater than [>] 1.5*upper limit of normal [ULN]); MCV, MCH, MCHC (<0.9*LLN, >1.1*ULN); platelets (<0.5*LLN>, >1.75*ULN); neutrophils, lymphocytes(<0.8*LLN, >1.2*ULN); eosinophils, basophils, monocytes (>1.2*ULN); total bilirubin (>1.5*ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (>3*ULN); total protein, albumin (<0.8*LLN, >1.2*ULN); creatinine, blood urea nitrogen (>1.3*ULN); glucose (<0.6*LLN, >1.5*ULN); uric acid (>1.2*ULN); sodium, potassium, chloride, calcium, bicarbonate (<0.9*LLN, >1.1*ULN); urine pH (<4.5, >8); qualitative urine glucose, ketones, protein, blood values (greater than or equal to [>=] 1) in urine dipstick test; urine RBC, WBC (>=20); hyaline casts (>1), bacteria (>20).	Baseline up to 28 days after the last dose of study treatment (Day 56)
Number of Participants With Vital Sign Abnormalities	Participants who met the criteria for abnormal findings in vital signs data were reported. Criteria for abnormalities in vital signs: supine systolic blood pressure (SBP) <90 millimeter of mercury (mmHg), supine diastolic BP (DBP) <50 mmHg, supine pulse rate <40 beats per minute (bpm) or >120 bpm. Maximum increase or decrease from baseline in supine SBP >=30 mmHg and maximum increase or decrease from baseline in supine DBP >=20 mmHg.	Baseline up to Follow-up (44 days)
Number of Participants With Electrocardiogram (ECG) Abnormalities	Participants with abnormal ECG findings were reported. Criteria for potential clinical concern in ECG parameters: maximum (max.) PR interval of >=300 milliseconds (msec), maximum QRS interval >=140 msec, maximum QTCF interval (Fridericia's Correction) of 450 to <480 msec, 480 to <500 msec and >=500 msec, maximum of >=25 percent (%) increase from baseline (IFB) value of >200 msec and >=50% for baseline value of less than or equal to (<=) 200 msec for PR interval, maximum increase from baseline of >=50% for QRS interval, maximum increase from baseline of >=30 msec to <60 msec and maximum increase from baseline of >60 msec in QTCF interval (Fridericia's Correction).	Baseline up to Follow-up (44 days)
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment [C-CASA]) is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide =1, suicide attempt =2 (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior =3 ("Yes" on "preparatory acts or behavior"), suicidal ideation =4 ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior =7 ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").	Screening, Baseline, Week 1, 2, 3, 4
Change From End of Treatment Visit in Physician's Withdrawal Checklist (PWC) Score at Follow-up Visit	PWC is a 20 item physician rated interview to measure anxiolytic drug withdrawal-related signs and symptoms. Each individual item score ranges from 0 (not present) to 3 (severe), where higher scores = more affected condition. PWC total score range from 0 (not present) to 60 (severe), where higher score = more affected condition. Change: score at follow-up visit minus score at the end of treatment visit.	End of treatment (Day 30), follow-up (Day 44)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Daily Low Back Pain Intensity (LBPI) as Measured by an 11-point Numeric Rating Scale (NRS) at Week 1, 2 3 and 4	Average back pain was assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Participants described their average low back pain during the past 24 hours by choosing the appropriate number from 0 to 10.	Baseline, Week 1, 2, 3, 4
Percent Change From Baseline in Daily Low Back Pain Intensity (LBPI) as Measured by an 11-point Numeric Rating Scale (NRS) at Week 1, 2, 3 and 4	Average back pain was assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Participants described their average low back pain during the past 24 hours by choosing the appropriate number from 0 to 10.	Baseline, Week 1, 2, 3, 4
Number of Participants With Sustained Response Rates in Daily Average LBPI NRS Scores at Greater Than or Equal to (>=) 30 Percent and >=50 Percent Reduction From Baseline	Average back pain was assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Participants described their average low back pain during the past 24 hours by choosing the appropriate number from 0 to 10. Percentage of reduction from baseline in the daily average LBPI NRS score was calculated as: ([daily value - baseline value] divided by baseline value) multiplied by 100. Number of participants with sustained response rates (for a minimum of 4 consecutive days) in the daily average LBPI NRS scores that were at >=30 percent and >=50 percent reduced from baseline were reported.	Baseline up to Week 4
Number of Participants Withdrawn Due to Lack of Efficacy	Participants withdrew from the study due to lack of efficacy (insufficient clinical response) were reported.	Baseline up to Week 4
Time to Withdrawal Due to Lack of Efficacy	Kaplan Meier and Cox Proportional Hazards analyses were to be used to compute the time to withdrawal due to lack of efficacy. Withdrawal due to lack of efficacy was identified from the participant summary case report form (CRF) page and where reason was identified as "Insufficient Clinical Response". Time to withdrawal was calculated as Date of withdrawal - Date of Randomization.	Baseline up to Week 4
Number of Participants Using Rescue Medication	Participants were permitted to use any commercial product (tablet/caplet/capsule) of acetaminophen (paracetamol) 500 mg as a rescue medication. Number of participants who used rescue medication were reported.	Week 1, 2, 3, 4
Number of Days Participants Used the Rescue Medication	The number of days for which the participants used the rescue medication were reported. Participants recorded the usage of acetaminophen rescue medication in the daily diary.	Week 1, 2, 3, 4
Amount of Rescue Medication Used by the Participants	The amount of rescue medication (Acetaminophen [paracetamol]) used was reported. Participants were permitted to use any commercial product of acetaminophen tablet/caplet/capsule.	Week 1, 2, 3, 4
Change From Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 1, 2, and 3	Each participant assessed his or her own disability due to low back pain using the RMDQ worksheet. The RMDQ total score was calculated as the total number of statements that were checked; the RMDQ total possible scores ranges from 0 to 24, with higher scores indicating greater disability.	Baseline, Week 1, 2, 3
Change From Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 4	Each participant assessed his or her own disability due to low back pain using the RMDQ worksheet. The RMDQ total score was calculated as the total number of statements that were checked; the RMDQ total possible scores ranges from 0 to 24, with higher scores indicating greater disability.	Baseline, Week 4
Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) at Week 2 and 4	This test assesses verbal learning and memory. Participants are given a list of 12 words and asked to repeat as many words as they can recall during 3 separate learning trials. The total recall score ranges from 0 (no memory) to 36 (best memory) while the delayed recall trial score ranges from 0 (no memory) to 12 (best memory); higher scores indicated greater verbal learning and recall.	Baseline, Week 2, Week 4
Chronic Low Back Pain (CLBP) Responder Index Analysis	Participants were successful responders if they had any of the following: >=30 percent reduction in mean daily average LBPI from baseline to particular week; decrease of >=30 percent in participant's global assessment of low back pain (disease activity) from baseline to particular week or no worsening (increase) in RMDQ total score from baseline to particular week.	Week 1, 2, 3, 4
Change From Baseline in Participant's Global Assessment (PtGA) of Low Back Pain Score at Week 1, 2, 3 and 4	Participant rated 5-point Likert scale ranging from 0 (no pain) to 4 (worst possible pain) with a higher score indicating greater level of pain.	Baseline, Week 1, 2, 3, 4
Patient Global Impression of Change (PGI-C) Score	PGI-C was a participant rated instrument to measure participant's assessment of change in his or her overall status since the previous visit on a 7-point scale; ranging from 1 (very much improved) to 7 (very much worse), where higher scores indicated more worsening.	Week 1, 2, 3, 4
Number of Participants With Global Evaluation of Study Medication (GESM) at Week 4	Participants rated their study treatment by GESM questionnaire. It was a qualitative measure of efficacy utilizing a 4-point Likert scale ranging from 1 (poor) to 4 (excellent), where higher score indicated a better overall response to the treatment. Number of participants who reported a particular score had been reported.	Week 4
Plasma Concentration of PF-06372865	Data was calculated by setting concentration values below the lower limit of quantification (LLOQ) to zero. The LLOQ was <0.0100 nanogram per milliliter (ng/mL).	Baseline, Week 1, 2, 3, 4
Plasma Concentration of Naproxen	Data was calculated by setting concentration values below the LLOQ to zero. The LLOQ was <1000 ng/mL.	Baseline, Week 1, 2, 3, 4

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: October 9, 2014
• First Submitted That Met QC Criteria: October 9, 2014
• First Posted (Estimate): October 13, 2014

Study Record Updates

• Last Update Posted (Estimate): January 4, 2017
• Last Update Submitted That Met QC Criteria: November 4, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; GABA Modulators; GABA Agents; Gout Suppressants; Naproxen; PF-06372865
• Other Study ID Numbers: B7431006