Tapentadol Prolonged Release (PR) Versus Oxycodone/Naloxone Prolonged Release in Severe Chronic Low Back Pain With a Neuropathic Component.

Evaluation of the Effectiveness, Safety, and Tolerability of Tapentadol PR Versus Oxycodone/Naloxone PR in Non-opioid Pre-treated Subjects With Uncontrolled Severe Chronic Low Back Pain With a Neuropathic Pain Component.

This was a clinical effectiveness trial designed to compare the effectiveness, safety, and tolerability of treatment with tapentadol prolonged release with that of oxycodone/naloxone prolonged release in non-opioid pre-treated subjects with severe chronic low back pain with a neuropathic pain component.

Both tapentadol and the opioid oxycodone are effective in chronic severe pain and tapentadol and oxycodone/naloxone have shown advantages in gastrointestinal tolerability versus oxycodone. Therefore, it was of high scientific interest to compare the latter 2 analgesics with respect to gastrointestinal tolerability. Tapentadol may have advantages regarding the neuropathic pain-related symptoms of low back pain due to its 2 mechanisms of action.

Inclusion Criteria:

• Informed consent signed.
• Male or female 18 years of age or older.
• Women of childbearing potential must have a negative pregnancy test at the Enrollment Visit.
• Women of childbearing potential must practice medically acceptable methods of birth control during the trial.
• Participant must be appropriately communicative and able to differentiate with regard to location and intensity of the pain, and to complete the questionnaires used in this trial.
• Participants must have a diagnosis of chronic low back pain; chronic pain defined as pain lasting for at least 3 months prior to enrollment.
• Participant's pain must require a strong analgesic (defined as World Health Organization Step III) as judged by the investigator.
• Participants who require a washout of co-analgesics at enrolment must have an average pain score (NRS-3) of 5 points or higher. Participants who do not require a washout of co-analgesics at enrollment must have an average pain intensity score (NRS-3) during the last 3 days of 6 points or higher.
• The painDETECT diagnostic screening questionnaire must be either "positive" (score of 19 to 38 inclusive) or "unclear" (score of 13 to 18 inclusive). If the participant is being treated with a stable regimen of centrally acting co-analgesics, a "negative" painDETECT score (score 9 points or higher).

Inclusion criteria prior to allocation to treatment:

• Participants must have an average pain intensity score (NRS-3) during the last 3 days of 6 points or higher.
• Participants must score either "positive" (score of 19 to 38 inclusive) or "unclear" (score of 13 to 18 inclusive) on the painDETECT diagnostic screening questionnaire.

Exclusion Criteria:

• Presence of a clinically significant disease or clinical laboratory values that in the investigator's opinion may affect effectiveness, quality of life, or safety/tolerability assessments.
• Presence of active systemic or local infections that may, in the opinion of the investigator, affect the effectiveness, quality of life, or safety/tolerability assessments.
• Employees of the investigator or trial site, with direct involvement in this trial or other trials under the direction of the investigator or trial site, as well as family members of employees of the investigator.
• Participation in another trial concurrently, or within 4 weeks prior to the Enrollment Visit.
• Known to or suspected of not being able to comply with the protocol and/or appropriate use of the Investigational Medicinal Products.
• Any painful procedures (e.g., major surgery) scheduled during the trial duration (Enrollment Visit until Final Evaluation Visit) that may, in the opinion of the investigator, affect the effectiveness, quality of life, or safety assessments.
• Pending litigation or application for insurance/governmental benefits due to chronic pain or disability and/or if the granted benefits might be influenced by a successful participation in the trial.
• Low back pain caused by cancer and/or metastatic diseases.
• History of alcohol or drug abuse, or suspicion thereof in the investigator's judgment.
• Presence of concomitant autoimmune inflammatory conditions.
• Participants with acute intoxication with alcohol, hypnotics, centrally acting analgesics, or psychotropic active substances.
• Participants with severe renal impairment, i.e., estimated glomerular filtration rate less than 30 mL/min (according to the National Kidney Foundation 2002).
• Known history of clinical laboratory values or current clinical laboratory values reflecting moderately or severely impaired hepatic function.
• History of seizure disorder or epilepsy.
• Any of the following within 1 year: mild/moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm (including brain metastases if present at the Enrollment Visit). Severe traumatic brain injury within 15 years (consisting of 1 or more of the following: brain contusion, intracranial hematoma, either unconsciousness or post traumatic amnesia lasting more than 24 hours) or residual sequelae suggesting transient changes in consciousness.
• Pregnant or breast-feeding women.
• Severe respiratory depression with hypoxia and/or hypercapnia, acute or severe bronchial asthma or severe chronic obstructive pulmonary disease.
• Presence or suspicion of paralytic ileus.
• Participants with severe cardiac impairment, e.g., New York Heart Association class >3, myocardial infarction less than 6 months prior to the Enrollment Visit, and/or unstable angina pectoris and/or cor pulmonale.
• Participant with known history of rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption.
• History of allergy or hypersensitivity to tapentadol, oxycodone, naloxone, and their formulations.
• Participants with acute biliary obstruction or acute pancreatitis.
• Participants with hypothyroidism (including myxedema) or Addison's disease.
• Participants taking any prohibited concomitant medication.