A Study of Oxycodone/Naloxone Controlled-release Tablets (OXN) to Assess Analgesic Efficacy and Management of Opioid-induced Constipation (OIC) in Opioid-experienced Subjects With Moderate to Severe Chronic Low Back Pain

Inclusion Criteria include:

• Male and female subjects ≥ 18 years of age with moderate to severe, chronic low back pain (lasting at least several hours daily) as their predominant pain condition for at least 3 months prior to screening period;
• The low back pain must be related to nonmalignant and nonneuropathic conditions and without radiation or with only proximal radiation (above the knee);

• Subjects must be:

  1. On ongoing opioid analgesic medication for at least 4 weeks prior to the screening visit and on a stable dose of opioid analgesic medication equivalent to 20 to 160 mg (inclusive) of morphine per day for the last 2 weeks prior to the screening visit, or
  2. Taking 0 to less than 20 mg of morphine or its equivalent per day for the last 2 weeks prior to the screening visit due to OIC.

Subjects taking any dose of tramadol or wearing ≤ 70 mcg/h buprenorphine patch (as long as it does not exceed highest approved dose for buprenorphine in the country the study site is located) on a stable regimen for the last 2 weeks prior to the screening visit will also meet this criterion;

• For subjects on <40 mg of morphine or equivalent per day, both the "average pain over the last 24 hours" and the "average pain over the past 14 days" scores at the screening visit must be ≥ 5;

• Subjects must have a reported history of OIC as defined by having had while on opioids <3 spontaneous bowel movements (SBM) per week and 1 or more of the following for at least 25% of SBMs:

  1. Hard or lumpy stools
  2. Straining during bowel movements
  3. A sensation of incomplete evacuation after bowel movements

where an SBM is defined as a bowel movement occurring in the absence of laxative or enema use in the previous 24 hours;

• Subjects must be willing to discontinue their current laxative regimen, including prokinetic drugs (e.g., metoclopramide);
• Subjects must agree to the use of oral bisacodyl as their only laxative rescue medication;
• Subjects who are willing and able to be compliant with the protocol, and who provide written informed consent.

Exclusion Criteria include:

• Subjects with any contraindication or any history of hypersensitivity to oxycodone, naloxone, or other opioids. This does not include subjects who have experienced common opioid side effects (e.g., nausea, constipation);
• Subjects with pain with distal radiation (below the knee) with or without neurologic signs, or presumptive or confirmed compression of a spinal nerve root;
• Subjects with acute spinal cord compression, acute compression fracture, seronegative spondyloarthropathy, acute nerve root compression, cauda equina compression, fibromyalgia, reflex sympathetic dystrophy or causalgia (complex regional pain syndrome), diabetic amyotrophy, meningitis, discitis, or back pain due to secondary infection, tumor, or postherpetic neuralgia;
• Subjects with gout, unless controlled on stable suppressive treatment with colchicine or uric-acid-lowering therapy without any attacks for ≥ 2 years and the subject has not been using NSAIDs or COX-2 inhibitors on a regular basis;
• Subjects with pseudogout, psoriatic arthritis, active Lyme disease, rheumatoid arthritis or other inflammatory arthritis, or neuropathic pain conditions (in addition to those stated in Exclusion Criterion above);
• Subjects with evidence of significant structural abnormalities of the gastrointestinal tract (e.g., bowel obstruction, strictures) or any diseases/conditions that affect bowel transit (e.g., ileus, uncontrolled hypothyroidism);
• Subjects with a history of prior chronic constipation (including functional constipation or pelvic floor dyssynergy) that was present for more than three months and that was not related to opioid use;
• Subjects currently with clinically diagnosed diarrhea, defined as 3 stools/day that are loose or watery in nature within 2 weeks before visit 3;
• Subjects with irritable bowel syndrome (IBS) or inflammatory bowel disease (eg, ulcerative colitis, Crohn's disease);
• Subjects who had surgery that may affect gastrointestinal motility or gastrointestinal pain within 2 months prior to the start of the screening period, or who plan such surgery during the study;
• Subjects with a history of fecal incontinence;
• Subjects who require ongoing therapy with medications (other than opioids) that have contributed to the subjects' constipation in the judgment of the investigator;

• The subject must not have had any of the following within the indicated time periods before screening:

  • nerve/plexus block within 4 weeks
  • neuroablation within 6 months
  • Botulinum toxin injection for pain control in the lumbar spine within 3 months
  • steroid injections of the lumbar spine within 6 weeks or any intravenous or intramuscular steroid injections within 4 weeks;
• Subjects who had surgical procedures directed towards the source of chronic low back pain within 6 months of the screening visit or planned during the study;
• Subjects with a history of malignancy within past 2 years, with exception of basal cell carcinoma that has been successfully treated;
• Subjects with current uncontrolled depression or other uncontrolled psychiatric disorder (subjects with controlled depression or other psychiatric disorder must be on stable medication for at least 1 month prior to the screening visit to participate in the study);
• Subjects currently taking, or who have taken naloxone, naltrexone, methylnaltrexone, or alvimopan within 10 days before the screening visit;
• Subjects who have used any investigational medication within 30 days prior to the first dose of study medication;
• Subjects who had received a monoamine oxidase inhibitor within the last 14 days prior to the screening visit;
• Subjects with any condition in which opioids are contraindicated, such as severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma, or paralytic ileus;
• Subjects with increase of intracranial pressure and/or epilepsy (not including history of pediatric febrile seizures);
• Subjects with clinically significant cardiovascular disease or dysrhythmias;
• Subjects with biliary tract disease, hypothyroidism, adrenal cortical insufficiency, or any other medical condition that in the investigator's opinion is inadequately treated and precludes entry into the study;
• Subjects who, in the opinion of the Investigator, are unsuitable to participate in this study for any other reason;
• Subjects who have received study drug in a clinical study of OXN or ONU.

Other protocol specific inclusion/exclusion criteria may apply.