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

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 withboundaries between the lowest rib and the crease of the buttocks) of Class 1 orproximal radicular (above the knee) pain of Class 2 based on the Quebec Task ForceClassification for Spinal Disorders (subjects with previous surgery or chronic painsyndrome, i.e., classes 9.2 or 10, will be allowed if their pain does not radiate orradiates only proximally) for a minimum of 12 months and

3. For the Suboptimal Responder group, pain must have been present for at leastseveral hours a day and have an Average PI score of 6-9 on an 11-point NRS withinthe past 24 hours of screening.

4. For the Optimal Responder group, subjects must have an Average PI score of 1-4 onan 11-point NRS within the past 24 hours of screening.

5. Have been taking ER/LA opioids or immediate release opioids (at least 4 times at day)for at least 12 months.

6. Have been taking one of the 3 index ER opioid drugs around-the-clock at a twice-a-dayfrequency for at least 3 consecutive months at a total daily dose within the rangeshown below. Daily Dose Range

7. Morphine sulfate extended-release: 120-540mg

8. Oxycodone extended-release: 80-360mg

9. Oxymorphone extended-release: 40-180mg

10. Be considered, in the opinion of the Investigator, to be in generally good healthother than CLBP at screening based upon the results of a medical history, physicalexamination, 12-lead ECG, and laboratory profile.

11. Speak, read, write, and understand English (to reduce heterogeneity of data),understand the consent form, and be able to effectively communicate with the studystaff.

12. Have access to the Internet (to access the patient support program).

13. Voluntarily provide written informed consent.

14. Be willing and able to complete study procedures.

Exclusion Criteria:

1. Have any clinically significant condition that would, in the opinion of theInvestigator, preclude study participation or interfere with the assessment of painand other symptoms of CLBP or increase the risk of opioid-related AEs.

2. Have a primary diagnosis of fibromyalgia, complex regional pain syndrome, neurogenicclaudication due to spinal stenosis, spinal cord compression, acute nerve rootcompression, severe or progressive lower extremity weakness or numbness, bowel orbladder dysfunction as a result of cauda equina compression, diabetic amyotrophy,meningitis, diskitis, back pain because of secondary infection or tumor, or paincaused by a confirmed or suspected neoplasm.

3. Have undergone a surgical procedure for back pain within 6 months prior to theScreening Visit.

4. Have had a nerve or plexus block, including epidural steroid injections or facetblocks, within 1 month prior to the Screening Visit or botulinum toxin injection inthe lower back region within 3 months prior to screening.

5. Have a history of confirmed malignancy within past 2 years, with exception of basalcell 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 Hgat screening.

7. Have a body mass index (BMI) >45 kg/m2. Anyone with a BMI >40 but <45 will complete ascreening tool (STOPBang Questionnaire) to rule out high risk of obstructive sleepapnea.

8. Have clinically significant depression based on a score of ≥20 on the Patient HealthQuestionnaire (PHQ-8)

9. Have suicidal ideation associated with actual intent and a method or plan in the pastyear: "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 (forevents that occurred in the past 5 years) to any of the suicidal behavior items of theC-SSRS.

11. Have any lifetime history of serious or recurrent suicidal behavior. (Non-suicidalself-injurious behavior is not a trigger for a risk assessment unless in theInvestigator's judgment it is indicated.)

12. Have clinically significant abnormality in clinical chemistry, hematology orurinalysis, including serum glutamic-oxaloacetic transaminase/aspartateaminotransferase or serum glutamic pyruvic transaminase/alanine aminotransferase ≥3times the upper limit of the reference range or a serum creatinine >2 mg/dL atscreening.

13. Have severe enough psychiatric or substance abuse disorder to compromise the subject'ssafety or scientific integrity of the study.

14. Have on-going litigation associated with back pain or pending applications for workerscompensation or disability issues or subjects who plan on filing litigation or claimswithin the next 12 months; subjects with settled past litigations will be allowed aswill 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 studymedication.

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 arecurrently enrolled in another investigational drug study.