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

NCT ID: NCT02741076

Last Updated: 2019-11-06

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-14

Study Completion Date

2018-04-27

Brief Summary

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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).

Detailed Description

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This was a multicenter, randomized, double-blind, placebo-controlled study which consisted of a common Screening Visit for all subjects, then different schedules for Optimal and Suboptimal Responders, followed by a common schedule for the Blinded Structured Opioid Discontinuation Period (BSODP) and Follow-up Period.

The original protocol (10 Jan 2016) was amended twice: Amendment 1 (07 Jul 2016) and Amendment 2 (08 Feb 2017). Screening of subjects only started after Amendment 1 approval. Approximately half the subjects were screened under Amendment 1 and half under Amendment 2. The original statistical analysis plan (SAP) was amended twice as well based on the protocol amendments. The current SAP is version 1.3, dated 11 April 2018, which added a section to list the analyses that were not being completed as a result of the premature termination of this study.

The duration of the entire study for each subject was approximately 33 to 37 weeks. For Suboptimal Responders: the study duration included Screening Period of up to 3 weeks, Run-in Period of 1 week, Baseline Period of 1 week, Blinded Structured Opioid Discontinuation Period of 24 weeks, and Follow-up Period of 4 weeks.

For Optimal Responders: the study duration included Screening Period of up to 3 weeks, Observation Period of 1 week, Taper Period up to 2 weeks, Open Label Titration Period of 3 weeks, Blinded Structured Opioid Discontinuation Period of 24 weeks, and Follow-up Period of 4 weeks.

The primary endpoint was the change in the mean Average PI score on the 0-10 Numerical Ratings Scale (NRS) from Baseline to the 1 week period before the Week 12 visit. Data were summarized using descriptive statistics (number of observations \[n\], mean, standard deviation, median, first and third quartiles, minimum, and maximum for continuous variables; and frequency and percentage for categorical variables). Due to the inability to recruit a sufficient number of subjects over an acceptable period of time, the study was terminated prematurely and efficacy analyses were reduced and only a brief summary of the statistical analyses of the primary endpoint in each group (Suboptimal Responders and Optimal Responders) were performed.

Conditions

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Opioid-Related Disorders Opiate Addiction Narcotic Abuse Drug Abuse

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Structured discontinuation opioid therapy Suboptimal Responder

Group Type EXPERIMENTAL

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

Intervention Type DRUG

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

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

Intervention Type DRUG

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

Structured discontinuation opioid therapy Optimal responders

Group Type EXPERIMENTAL

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

Intervention Type DRUG

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

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

Intervention Type DRUG

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

Continuation of opioid therapy Suboptimal responders

Group Type EXPERIMENTAL

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

Intervention Type DRUG

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

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

Intervention Type DRUG

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

Structured Continuation of opioid therapy Optimal responders

Group Type EXPERIMENTAL

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

Intervention Type DRUG

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

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

Intervention Type DRUG

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

Interventions

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

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

Intervention Type DRUG

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

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Be male or non-pregnant, non-lactating female aged 18 to 75 years, inclusive.
2. 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

1. 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.
2. 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.
3. Have been taking ER/LA opioids or immediate release opioids (at least 4 times at day) for at least 12 months.
4. 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
1. Morphine sulfate extended-release: 120-540mg
2. Oxycodone extended-release: 80-360mg
3. Oxymorphone extended-release: 40-180mg
5. 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.
6. 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.
7. Have access to the Internet (to access the patient support program).
8. Voluntarily provide written informed consent.
9. Be willing and able to complete study procedures.

Exclusion Criteria

1. 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.
2. 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.
3. Have undergone a surgical procedure for back pain within 6 months prior to the Screening Visit.
4. 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.
5. 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.
6. 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.
7. 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.
8. Have clinically significant depression based on a score of ≥20 on the Patient Health Questionnaire (PHQ-8)
9. 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).
10. 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.
11. 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.)
12. 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.
13. Have severe enough psychiatric or substance abuse disorder to compromise the subject's safety or scientific integrity of the study.
14. 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.
15. Have used a monoamine oxidase inhibitor within 14 days prior to the start of study medication.
16. Are taking agonist-antagonists (pentazocine, butorphanol or nalbuphine), buprenorphine, methadone, barbiturates, or more than one type of benzodiazepine within 1 month prior to screening.
17. Have a positive urine drug test (UDT) for illicit drugs (including marijuana), non-prescribed controlled substances (opioid or non-opioid), or alcohol at screening.
18. Have taken any investigational drug within 30 days prior to the Screening Visit or are currently enrolled in another investigational drug study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Member Companies of the Opioid PMR Consortium

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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G & L Research

Foley, Alabama, United States

Site Status

Horizon Research Partners

Mobile, Alabama, United States

Site Status

Healthscan Clinical Trials

Montgomery, Alabama, United States

Site Status

Center for Pain and Supportive Care

Phoenix, Arizona, United States

Site Status

The Pain Center of Arizona

Phoenix, Arizona, United States

Site Status

Quality of Life Medical and Research Centers

Tucson, Arizona, United States

Site Status

Coastal Pain and Spinal Diagnostics

Carlsbad, California, United States

Site Status

Aviva Research

Escondido, California, United States

Site Status

Global Clinical Trials

Irvine, California, United States

Site Status

The Helm Center for Pain Management

Laguna Woods, California, United States

Site Status

Alexander Ford, MD

Los Angeles, California, United States

Site Status

Samaritan Center for Medical Research

Los Gatos, California, United States

Site Status

Catalina Research Institute

Montclair, California, United States

Site Status

North Country Clinical Research

Oceanside, California, United States

Site Status

Westview Clinical Research

Placentia, California, United States

Site Status

Foothills Pain Management Clinic

Pomona, California, United States

Site Status

Northern California Research

Sacramento, California, United States

Site Status

Breakthrough Clinical Trials

San Bernardino, California, United States

Site Status

Optimus Medical Group

San Francisco, California, United States

Site Status

Mountain View Clinical Research

Denver, Colorado, United States

Site Status

Care Research Center

Doral, Florida, United States

Site Status

Direct Helpers Research Center

Hialeah, Florida, United States

Site Status

Eastern Research

Hialeah, Florida, United States

Site Status

Finlay Medical Research

Miami, Florida, United States

Site Status

Future Clinical Research

Miami, Florida, United States

Site Status

South Florida Clinical Research

Miami, Florida, United States

Site Status

Empire Clinical Research

Miami Lakes, Florida, United States

Site Status

Martin E Hale, MD

Plantation, Florida, United States

Site Status

Florida Medical Pain Management

St. Petersburg, Florida, United States

Site Status

Clinical Research of West Florida

Tampa, Florida, United States

Site Status

Palm Beach Research Center

West Palm Beach, Florida, United States

Site Status

Georgia Institute for Clinical Research

Marietta, Georgia, United States

Site Status

Sestron Clinical Research

Marietta, Georgia, United States

Site Status

Healthcare Research Network II

Blue Island, Illinois, United States

Site Status

Indiana Pain and Spine Clinic

South Bend, Indiana, United States

Site Status

Mid-American Psysiatrists

Overland Park, Kansas, United States

Site Status

WK River Cities Clinical Research Center

Shreveport, Louisiana, United States

Site Status

MedVadis Research Corporation

Watertown, Massachusetts, United States

Site Status

Oakland Medical Research

Troy, Michigan, United States

Site Status

Healthcare Research Network

Hazelwood, Missouri, United States

Site Status

St Louis Clinical Trials

St Louis, Missouri, United States

Site Status

Red Rock Clinical Research

Las Vegas, Nevada, United States

Site Status

OnSite Clinical Solutions

Mooresville, North Carolina, United States

Site Status

Clinical Trials of America

Winston-Salem, North Carolina, United States

Site Status

The Center for Clinical Research

Winston-Salem, North Carolina, United States

Site Status

Prestige Clinical Research

Franklin, Ohio, United States

Site Status

North Star Medical Research

Middleburg Heights, Ohio, United States

Site Status

Cutting Edge Research Group

Oklahoma City, Oklahoma, United States

Site Status

Medical Research International

Oklahoma City, Oklahoma, United States

Site Status

SP Research

Oklahoma City, Oklahoma, United States

Site Status

Brandywine Clinical Research

Downingtown, Pennsylvania, United States

Site Status

Founders Research Corporation

Philadelphia, Pennsylvania, United States

Site Status

Carolina Center for Advanced Management of Pain

Spartanburg, South Carolina, United States

Site Status

Healthy Concepts

Rapid City, South Dakota, United States

Site Status

Comprehensive Pain Specialists

Hendersonville, Tennessee, United States

Site Status

New Phase Research and Development

Knoxville, Tennessee, United States

Site Status

Biopharma Informatic Research Center

Houston, Texas, United States

Site Status

Coastal Medical Group

Houston, Texas, United States

Site Status

Highland Clinical Research

Salt Lake City, Utah, United States

Site Status

Interventional Pain and Spine Specialists

Chester, Virginia, United States

Site Status

Healing Hands of Virginia

Richmond, Virginia, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2065-5

Identifier Type: -

Identifier Source: org_study_id

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