Intervention: Tilarginine
Trial phase: Phase 4
SMILES: CNC(=N)NCCC[C@H](N)C(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 220
Group description: Single-arm study

Oxycodone/Naloxone: 8 weeks treatment with Oxycodone/Naloxone
Eligibility criteria:
Inclusion Criteria:

Male or female ≥ 20 and <80 years of age
Patients who have spinal disorders related pain for over 90days
Patients who have moderate to severe pain intensity which is not controlled with weak opioids or NSAIDs: NRS ≥ 4
Naïve patients for Oxycodone/Naloxone
Naïve patients for strong opioid
Patients who signed a written informed consent form

Exclusion Criteria:

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test
Patients with known hypersensitivity to Oxycodone/Naloxone or to any of the excipients
Patients with severe respiratory depression with hypoxia and/or hypercapnoea
Patients with severe chronic obstructive pulmonary disease
Patients with cor pulmonale
Patients with severe bronchial asthma
Patients who have been diagnosed or is suspected of having paralytic or obstructive ileus.Patients with moderate to severe hepatic impairment
Targin(R) product contains lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take
Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), or alkaline phosphatase levels (>2.5 times the upper limit of normal, it is allowed >5 times the upper limit of normal in case of transition in liver) or an abnormal total bilirubin and/or creatinine level (s)(greater than 1.5 times the upper limit of normal), gamma glutamyl transpeptidase (GGT or GGTP) ≥ 3 times the upper limit of normal
Patients with uncontrolled seizures
Requiring interventional treatment for pain such as neurodestructive procedure or regional infusion
Patients with increased intracranial pressure
In the investigator's opinion, subjects who are receiving hypnotics or central nervous system (CNS) depressants that may pose a risk of additional CNS depression with opioid study medication
Patients with myxodema, not adequately treated hypothyroidism or Addisons disease
Patients receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine)
Clinically significant impairment of cardiovascular, respiratory and renal function
Major surgery within 1 month prior to screening or planned surgery
Mainly pain originated other than spinal disorders disease
Non-malignant patients or cancer patients who are receiving any oncology treatment that could affect the measure of pain control
Patients with uncontrolled constipation regardless of laxative use and/or laxative type
With a disability that may prevent the patient from completing all study requirements and in particular, interfere with 24hrs pain intensity score
Patients known to have, or suspected of having a history of drug abuse
Patients with history of opioid or drug dependence
Any situation where opioids are contraindicated
Patient who needs acute dose titration or whose pain intensity fluctuate significantly in a short period according to investigator's judgment
Having used other investigational drugs at the time of enrollment

No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.