Discontinuation vs Continuation of Long-term Opioid Therapy in Suboptimal and Optimal Responders With Chronic Pain

NCT02741076 | Terminated Phase 4 Results

• 1 other identifier: 2065-5
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 61

Brief Summary

The purpose of this study is to evaluate the effect on pain intensity (PI) of structured discontinuation of long-term opioid analgesic therapy compared to continuation of opioid therapy in Suboptimal and Optimal Responders to high-dose, long-term opioid analgesic therapy for chronic low back pain (CLBP).

Conditions

Opioid-Related Disorders; Opiate Addiction; Narcotic Abuse; Drug Abuse

Outcome Measures

Primary Outcomes (1)

• Change in the Mean Average Pain Intensity (PI) Score on the 0-10 Numerical Ratings Scale (NRS)

  Baseline is defined as the mean of the available Average PI scores on the 0-10 Numerical Ratings Scale (NRS) over the 7-day Baseline Period. For the scheduled post-randomization visits, mean Average Pain Intensity is defined as the means of the respective PI scores over the 7 days preceding the visit. If there is only one daily PI score available, the mean is not calculated, and the data point is considered missing. PI = Pain Intensity. Higher scores indicate more pain intensity; lower scores less pain intensity. Scale range 0-10.

  From baseline to the 1 week period prior to the Week 12 visit

Secondary Outcomes (12)

• Change in Mean Average Pain Intensity Score (PI) Score on the 0-10 Numerical Ratings Scale (NRS)

  From baseline to weeks 4, 8, 16, 20, and 24

• Number of Suboptimal Responders With Pain Intensity (PI) Score Improvement Relative to Baseline PI Measured on the 0-10 Numerical Ratings Scale (NRS)

  Weeks 12 and 24

• Number of Suboptimal Responders With Pain Intensity (PI) Score Worsening Relative to Baseline PI Measured on the 0-10 Numerical Ratings Scale (NRS)

  Weeks 12 and 24

• Change From Baseline on Sleep Quality Measured by Medical Outcomes Study (MOS)

  Weeks 12 and 24

• Participants Sleep Quantity Measured by Medical Outcomes Study (MOS)

  4 weeks prior to baseline and prior to 12 and 24 week visits

Study Arms (4)

Structured discontinuation opioid therapy Suboptimal Responder

EXPERIMENTAL

Drug: Structured discontinuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER); Drug: Continuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER)

Structured discontinuation opioid therapy Optimal responders

EXPERIMENTAL

Drug: Structured discontinuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER); Drug: Continuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER)

Continuation of opioid therapy Suboptimal responders

EXPERIMENTAL

Drug: Structured discontinuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER); Drug: Continuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER)

Structured Continuation of opioid therapy Optimal responders

EXPERIMENTAL

Drug: Structured discontinuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER); Drug: Continuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER)

Interventions

Structured discontinuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER) DRUG

Structured discontinuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER)

Continuation of opioid therapy Suboptimal responders; Structured Continuation of opioid therapy Optimal responders; Structured discontinuation opioid therapy Optimal responders; Structured discontinuation opioid therapy Suboptimal Responder

Continuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER) DRUG

Continuation of opioid therapy (morphine sulfate ER, oxycodone ER, oxymorphone ER)

Continuation of opioid therapy Suboptimal responders; Structured Continuation of opioid therapy Optimal responders; Structured discontinuation opioid therapy Optimal responders; Structured discontinuation opioid therapy Suboptimal Responder

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be male or non-pregnant, non-lactating female aged 18 to 75 years, inclusive.
• Have a clinical diagnosis of non-radicular CLBP (pain that occurs in an area with boundaries between the lowest rib and the crease of the buttocks) of Class 1 or proximal radicular (above the knee) pain of Class 2 based on the Quebec Task Force Classification for Spinal Disorders (subjects with previous surgery or chronic pain syndrome, i.e., classes 9.2 or 10, will be allowed if their pain does not radiate or radiates only proximally) for a minimum of 12 months and
• For the Suboptimal Responder group, pain must have been present for at least several hours a day and have an Average PI score of 6-9 on an 11-point NRS within the past 24 hours of screening.
• For the Optimal Responder group, subjects must have an Average PI score of 1-4 on an 11-point NRS within the past 24 hours of screening.
• Have been taking ER/LA opioids or immediate release opioids (at least 4 times at day) for at least 12 months.
• Have been taking one of the 3 index ER opioid drugs around-the-clock at a twice-a-day frequency for at least 3 consecutive months at a total daily dose within the range shown below.
• Daily Dose Range
• Morphine sulfate extended-release: 120-540mg
• Oxycodone extended-release: 80-360mg
• Oxymorphone extended-release: 40-180mg
• Be considered, in the opinion of the Investigator, to be in generally good health other than CLBP at screening based upon the results of a medical history, physical examination, 12-lead ECG, and laboratory profile.
• Speak, read, write, and understand English (to reduce heterogeneity of data), understand the consent form, and be able to effectively communicate with the study staff.
• Have access to the Internet (to access the patient support program).
• Voluntarily provide written informed consent.
• Be willing and able to complete study procedures.

You may not qualify if:

• Have any clinically significant condition that would, in the opinion of the Investigator, preclude study participation or interfere with the assessment of pain and other symptoms of CLBP or increase the risk of opioid-related AEs.
• Have a primary diagnosis of fibromyalgia, complex regional pain syndrome, neurogenic claudication due to spinal stenosis, spinal cord compression, acute nerve root compression, severe or progressive lower extremity weakness or numbness, bowel or bladder dysfunction as a result of cauda equina compression, diabetic amyotrophy, meningitis, diskitis, back pain because of secondary infection or tumor, or pain caused by a confirmed or suspected neoplasm.
• Have undergone a surgical procedure for back pain within 6 months prior to the Screening Visit.
• Have had a nerve or plexus block, including epidural steroid injections or facet blocks, within 1 month prior to the Screening Visit or botulinum toxin injection in the lower back region within 3 months prior to screening.
• Have a history of confirmed malignancy within past 2 years, with exception of basal cell or squamous cell carcinoma of the skin that has been successfully treated.
• Have uncontrolled blood pressure, i.e., subject has a sitting systolic blood pressure \>180 mm Hg or \<90 mm Hg, or a sitting diastolic blood pressure \>110 mmHg or \<40 mm Hg at screening.
• Have a body mass index (BMI) \>45 kg/m2. Anyone with a BMI \>40 but \<45 will complete a screening tool (STOPBang Questionnaire) to rule out high risk of obstructive sleep apnea.
• Have clinically significant depression based on a score of ≥20 on the Patient Health Questionnaire (PHQ-8)
• Have suicidal ideation associated with actual intent and a method or plan in the past year: "Yes" answers on items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Have a previous history of suicidal behaviors in the past 5 years: "Yes" answer (for events that occurred in the past 5 years) to any of the suicidal behavior items of the C-SSRS.
• Have any lifetime history of serious or recurrent suicidal behavior. (Non-suicidal self-injurious behavior is not a trigger for a risk assessment unless in the Investigator's judgment it is indicated.)
• Have clinically significant abnormality in clinical chemistry, hematology or urinalysis, including serum glutamic-oxaloacetic transaminase/aspartate aminotransferase or serum glutamic pyruvic transaminase/alanine aminotransferase ≥3 times the upper limit of the reference range or a serum creatinine \>2 mg/dL at screening.
• Have severe enough psychiatric or substance abuse disorder to compromise the subject's safety or scientific integrity of the study.
• Have on-going litigation associated with back pain or pending applications for workers compensation or disability issues or subjects who plan on filing litigation or claims within the next 12 months; subjects with settled past litigations will be allowed as will subjects who have been on workers compensation or disability claims for at least 3 months.
• Have used a monoamine oxidase inhibitor within 14 days prior to the start of study medication.

Sponsors & Collaborators

• Member Companies of the Opioid PMR Consortium: lead

Study Sites (61)

G & L Research

Foley, Alabama, United States

Location

Horizon Research Partners

Mobile, Alabama, United States

Location

Healthscan Clinical Trials

Montgomery, Alabama, United States

Location

Center for Pain and Supportive Care

Phoenix, Arizona, United States

Location

The Pain Center of Arizona

Phoenix, Arizona, United States

Location

Quality of Life Medical and Research Centers

Tucson, Arizona, United States

Location

Coastal Pain and Spinal Diagnostics

Carlsbad, California, United States

Location

Aviva Research

Escondido, California, United States

Location

Global Clinical Trials

Irvine, California, United States

Location

The Helm Center for Pain Management

Laguna Woods, California, United States

Location

Alexander Ford, MD

Los Angeles, California, United States

Location

Samaritan Center for Medical Research

Los Gatos, California, United States

Location

Catalina Research Institute

Montclair, California, United States

Location

North Country Clinical Research

Oceanside, California, United States

Location

Westview Clinical Research

Placentia, California, United States

Location

Foothills Pain Management Clinic

Pomona, California, United States

Location

Northern California Research

Sacramento, California, United States

Location

Breakthrough Clinical Trials

San Bernardino, California, United States

Location

Optimus Medical Group

San Francisco, California, United States

Location

Mountain View Clinical Research

Denver, Colorado, United States

Location

Care Research Center

Doral, Florida, United States

Location

Direct Helpers Research Center

Hialeah, Florida, United States

Location

Eastern Research

Hialeah, Florida, United States

Location

Finlay Medical Research

Miami, Florida, United States

Location

Future Clinical Research

Miami, Florida, United States

Location

South Florida Clinical Research

Miami, Florida, United States

Location

Empire Clinical Research

Miami Lakes, Florida, United States

Location

Martin E Hale, MD

Plantation, Florida, United States

Location

Florida Medical Pain Management

St. Petersburg, Florida, United States

Location

Clinical Research of West Florida

Tampa, Florida, United States

Location

Palm Beach Research Center

West Palm Beach, Florida, United States

Location

Georgia Institute for Clinical Research

Marietta, Georgia, United States

Location

Sestron Clinical Research

Marietta, Georgia, United States

Location

Healthcare Research Network II

Blue Island, Illinois, United States

Location

Indiana Pain and Spine Clinic

South Bend, Indiana, United States

Location

Mid-American Psysiatrists

Overland Park, Kansas, United States

Location

WK River Cities Clinical Research Center

Shreveport, Louisiana, United States

Location

MedVadis Research Corporation

Watertown, Massachusetts, United States

Location

Oakland Medical Research

Troy, Michigan, United States

Location

Healthcare Research Network

Hazelwood, Missouri, United States

Location

St Louis Clinical Trials

St Louis, Missouri, United States

Location

Red Rock Clinical Research

Las Vegas, Nevada, United States

Location

OnSite Clinical Solutions

Mooresville, North Carolina, United States

Location

Clinical Trials of America

Winston-Salem, North Carolina, United States

Location

The Center for Clinical Research

Winston-Salem, North Carolina, United States

Location

Prestige Clinical Research

Franklin, Ohio, United States

Location

North Star Medical Research

Middleburg Heights, Ohio, United States

Location

Cutting Edge Research Group

Oklahoma City, Oklahoma, United States

Location

Medical Research International

Oklahoma City, Oklahoma, United States

Location

SP Research

Oklahoma City, Oklahoma, United States

Location

Brandywine Clinical Research

Downingtown, Pennsylvania, United States

Location

Founders Research Corporation

Philadelphia, Pennsylvania, United States

Location

Carolina Center for Advanced Management of Pain

Spartanburg, South Carolina, United States

Location

Healthy Concepts

Rapid City, South Dakota, United States

Location

Comprehensive Pain Specialists

Hendersonville, Tennessee, United States

Location

New Phase Research and Development

Knoxville, Tennessee, United States

Location

Biopharma Informatic Research Center

Houston, Texas, United States

Location

Coastal Medical Group

Houston, Texas, United States

Location

Highland Clinical Research

Salt Lake City, Utah, United States

Location

Interventional Pain and Spine Specialists

Chester, Virginia, United States

Location

Healing Hands of Virginia

Richmond, Virginia, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Narcotic-Related Disorders; Substance-Related Disorders

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Limitations and Caveats

This study was terminated because it could not recruit the planned study population. Randomized study participants were too few to show changes in pain intensity scores or clinical effects. The safety profile reflects current prescribing information.

Results Point of Contact

• Title: John Han, Associate Director, Statistics
• Organization: Janssen Pharmaceuticals, Inc.

jhan9@its.jnj.com

484-354-3547

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2016
• First Posted: April 18, 2016
• Study Start: September 14, 2016
• Primary Completion: April 27, 2018
• Study Completion: April 27, 2018
• Last Updated: November 6, 2019
• Results First Posted: November 6, 2019

Record last verified: 2019-10

Locations

US (61)