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Flurbiprofen Tape for Treatment of Chronic Low Back Pain

Phase 2
Completed
Conditions
Chronic Low Back Pain
Interventions
Drug: Placebo Tape (Arm 1)
Drug: Placebo Tape (Arm 3)
Registration Number
NCT00759330
Lead Sponsor
Teikoku Pharma USA, Inc.
Brief Summary

The purpose of this trial is to evaluate the analgesic efficacy and safety of flurbiprofen tape for chronic low back pain (lasting greater than 3 months).

Detailed Description

This study is a multi-center, randomized, double-blind, placebo-controlled study in patients with daily low back pain below the 12th thoracic vertebra of greater than 3 months duration. Patients also had an average daily pain score of 4 or greater on an 11-point categorical pain scale for the last 3 days of the baseline phase. The study began with a 14-day washout period of previously used pain medications. At the end of the 14-day baseline phase, patients were randomized to 1 of 4 treatments: Flurbiprofen tape applied once daily for 12 hours, Flurbiprofen tape applied once daily for 24 hours, placebo tape applied once daily for 12 hours, or placebo tape applied once daily for 24 hours. During the 7-day treatment phase, patients applied 2 treatment tapes once daily for 7 days. The tapes remained on for 12 or 24 hours of continuous treatment, depending on the treatment to which they were randomized. Patients were provided with rescue medication. After 7 days of tape treatment, patients returned to the clinic for a study exit visit.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
127
Inclusion Criteria
  • male or female 18 to 80 years;
  • signed an informed consent;
  • daily LBP below the 12th thoracic vertebra of greater than 3 months' duration;
  • able to ambulate at least 100 meters;
  • in stable general health with laboratory values within normal limits
  • no evidence of drug abuse or residual opiates; determined by urine drug screening;
  • diagnosis of chronic LBP verified by medical records;
  • female patients must be postmenopausal (defined as 1 year without menses), physically incapable of becoming pregnant, or using an acceptable birth control method. Non-postmenopausal patients must have confirmation of a negative urine pregnancy test;
  • must read and speak English;
  • must be reliable and mentally competent to complete study measurements;
  • must be available for the study visits and telephone checks from study entry to study completion.
  • male patients must use an acceptable method of birth control with their female partners;
  • rates their pain at 3 or higher on an 11-point Categorical Pain Scale for LBP over the prior week (7 days) of Visit 1.
  • over the last 3 days of the Baseline Phase, had a computed average pain score of 4 or greater on an 11-point Categorical Pain Scale
  • discontinued the use of any topical pain medications, salves, anticonvulsants, oral NSAIDs, muscle relaxants, opioids, or anti-inflammatory steroids during the Baseline Phase. Acetaminophen, at a dose of ≤ 1000 mg per day is acceptable;
  • able to discontinue the use of therapy defined as ice, heat, chiropractic care, physical therapy, acupuncture and acupressure on their lower back area during the Baseline Phase.
Exclusion Criteria
  • open skin lesion within the painful area;
  • experiencing LBP for less than 3 months;
  • undergone back surgery within the past 3 months or has plans for back surgery within 30 days post-study;
  • participated in clinical treatment studies within 30 days of study entry;
  • chronic back pain which is due to fibromyalgia or connective tissue disorder (lupus, rheumatoid arthritis, ankylosing spondylitis, Reiter's syndrome, etc.);
  • LBP due to malignancy, vertebral fracture, or infection;
  • used opioids (including low potency/low dose opioid combinations and tramadol) more than 2 times per week within 30 days of study entry. Opioids and tramadol must not have been taken at least 4 days prior to study entry;
  • had injection therapy within 30 days of study entry, including corticosteroids;
  • a clinically significant psychiatric disorder (severe depression, other Axis I or Axis II disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV);
  • taking lithium, furosemide, and/or thiazides;
  • considered unreliable as to medication compliance (if any medication other than 1000 mg or less of acetaminophen a day was taken for any type of pain, the patient was discontinued) or adherence to scheduled appointments as determined by the investigators;
  • a prior history of GI bleeds/ulcers or clinically significant liver/kidney disease;
  • known hypersensitivity to flurbiprofen or other NSAIDs;
  • has a coagulation disorder or is taking warfarin or other anticoagulants (aspirin at a dose of [≤ 81 mg] is acceptable);
  • clinically significant fluid retention, cardiovascular disease (CVD), hypertension, or heart failure;
  • had coronary artery bypass graft surgery (CABG), cardiovascular thrombotic event, myocardial infarction (MI) and/or stroke within 1 year of Visit 1;
  • had unresolved litigation related to back injury or other pain complaints; settled disability claims/payments (Worker's Compensation, state/federal/private disability plans) were allowed.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Flurbiprofen Tape (Arm 2)Flurbiprofen Tape (Arm 2)Flurbiprofen tape remained on for 12 hours of continuous treatment per day.
Flurbiprofen Tape (Arm 4)Flurbiprofen Tape (Arm 4)Flurbiprofen tape remained on for 24 hours of continuous treatment per day.
Placebo Tape (Arm 1)Placebo Tape (Arm 1)Placebo tape remained on for 12 hours of continuous treatment per day.
Placebo Tape (Arm 3)Placebo Tape (Arm 3)Placebo tape remained on for 24 hours of continuous treatment per day.
Primary Outcome Measures
NameTimeMethod
Cumulative Summed Pain Intensity Difference (SPID+)Days 4 and 7 of tape treatment phase

The primary efficacy endpoint was the cumulative summed pain intensity difference (SPID+) at Days 4 and 7 of the tape treatment phase as computed from the daily categorical pain scale score reported on the patient's daily diary during the tape treatment phase; pain was rated on an 11-point scale, where: 0 = no pain, 10 = worst pain imaginable.

Summed pain intensity difference is the sum of the pain intensity differences (PID). PID at each post-baseline evaluation was computed as the average baseline categorical pain scale score minus the post-baseline categorical pain scale score from the daily dairy. For patients with multiple pain scores reported on a given post-baseline study day, the PID scores were averaged to compute one daily PID score for each patient.

Secondary Outcome Measures
NameTimeMethod
Average Daily Categorical Pain Scale ScoresDays 1 through 7 of tape treatment phase

Patients rated their lower back pain, caused by normal activity and movement, on an 11-point categorical pain scale, where:

0 = no pain, and 10 = worst pain imaginable. Patients rated their lower back pain every 12 hours, at any time they took medication including rescue medication for any type of pain, and if they applied or removed their treatment tapes at a time other than the scheduled time.

Data are reported as the daily average categorical pain scale score by treatment group.

Patient Global Impression of Change (PGIC)Day 7

At Day 7, patients provided their PGIC with regard to lower back pain response to treatment, using a 7-point scale, where:

1 = very much improved, 7 = very much worse.

Change From Baseline in Total Tender Point Examination ScoreBaseline to Day 7 of tape treatment phase

At baseline and Day 7 of the tape treatment phase, patients had an assessment of tenderness bilaterally at the sacroiliac joint, greater trochanter of the hip, gluteus medius and minimus, and paraspinal muscles at L3-L4, L4-L5, and L5-S1. The investigator or research nurse pressed 12 specific areas of the body (6 locations, left and right sides), and patients were asked to rate the intensity of their pain at those 12 areas using an 11-point scale, where:

0 = no pain, 10 = the worst pain the patient has ever experienced. The total tender point examination score ranged from 0 (best outcome) to 120 (worst outcome). Change from baseline = baseline - Day 7. A positive change indicates a favorable treatment effect.

Pain Intensity Difference (PID+)Days 1 through 7 of tape treatment phase

+PID = pre-treatment value at baseline - post-treatment value at day of evaluation, where: pre-treatment value at baseline = average daily pain over the last 3 days of the baseline phase (ie, average of daily averages of the categorical pain scale scores for the last 3 days of the baseline phase). Pain was rated on an 11-point scale, where: 0 = no pain, 10 = worst pain imaginable.

A positive PID indicates a reduction in pain.

Percent Change From Baseline in Total Functional Rating Index (FRI)baseline to Day 7 of tape treatment phase

Patients completed the FRI, a 10-item back pain-specific measure of function questionnaire describing the condition at the time the questionnaire was completed; each item (pain intensity, sleeping, personal care, travel, etc.) was rated on a 5-point scale, where 0 = best outcome, 4 = worst outcome.

FRI was reported as the percent change from baseline at Day 7 of the tape treatment phase, where:

Total FRI score = sum of the 10 questions. The total FRI score ranged from 0 (best outcome) to 40 (worst outcome). Percent change = (\[baseline - Day 7\]/baseline)\*100.

A positive percent change indicates a favorable treatment effect.

Acetaminophen Used During the Tape Treatment PhaseDay 1 through Day 7 of the tape treatment phase

The total amount (mg) of rescue medication used during the tape treatment phase.

Patient Assessment of Wearability of TherapyDay 7

At Day 7, patients assessed the wearability of their treatment tape (ease of application, stays in place, comfortable to wear) using a 4-point scale, where:

1 = Excellent, 4 = Poor.

Percentage of Patients Who DiscontinuedDays 1 through Day 7 of tape treatment phase

The percentage of patients who discontinued the study during the tape treatment phase due to lack of efficacy.

Trial Locations

Locations (10)

Sarah Cannon Research Institute

🇺🇸

Memphis, Tennessee, United States

Internal Medicine Associates of Cordova

🇺🇸

Cordova, Tennessee, United States

Rainier Clinical Research Center, Inc.

🇺🇸

Renton, Washington, United States

Senior Adults Specialty Research

🇺🇸

Austin, Texas, United States

Redpoint Research

🇺🇸

Phoenix, Arizona, United States

Diablo Clinical Research, Inc.

🇺🇸

Walnut Creek, California, United States

Palm Beach Research Center

🇺🇸

West Palm Beach, Florida, United States

University Foundation for Education and Research, Inc.

🇺🇸

Tampa, Florida, United States

Charolettesville Medical Research

🇺🇸

Charlottesville, Virginia, United States

Aurora Advanced Healthcare, Inc.

🇺🇸

Milwaukee, Wisconsin, United States

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