An Interventional Study to Assess the Efficacy and Safety of Oxycodone/Naloxone in Korean Patients With Spinal Disorders

Study Overview
=================
Brief Summary
-----------------
Study Objectives: Primary objective - To assess the pain reduction after 8 weeks treatment from baseline (week 0) Secondary objectives To assess the pain reduction after 4 weeks treatment from baseline (week 0) To assess the EQ-5D To assess physician's overall satisfaction To assess subject's overall satisfaction To assess safety

Detailed Description
-----------------
Study Design (Methodology): This will be a multicenter, phase IV, interventional study to assess the efficacy and safety of TARGIN(R)(Oxycodone/Naloxone) in Korean patients who are dissatisfied with their current analgesic medication (WHO step II analgesics). Upon providing written informed consent, subject will be screened in the study and assessment will be performed at that time such as safety laboratory assessments, physical examination, vital sign, medical history taking, 24 hours pain intensity score, EQ-5D, physician's overall satisfaction and subject's overall satisfaction. If patient is eligible in inclusion/exclusion criteria at the time of visit 1, the patient will receive treatment with TARGIN(R). Re-screening, study drug dose interruption is not allowed. The duration of study drug dose interruption is defined as for 1 week. Treatment with TARGIN(R) will be started at 5/2.5mg b.i.d.,and proper titration (up titration) will be allowed at each visit or at unscheduled visit according to the investigator's decision. On-site visit or phone call will be allowed for visit 2(wk 1).The up titration will be considered by investigator's judgement as followings; (1) if the rescue medication was used more than 2 times per day, on average or (2) based on the daily average numerical rating scale , if the numerical rating scale was changed to worsen since the previous visit, (3) Investigator's judgement by considering any titration needed situation (e.g. dose, frequency of rescue medication). Pain assessment by investigator at each visit will be used for analysis and criteria for uptitration. Daily pain diary will be used for only criteria for uptitration. Safety laboratories will be obtained at baseline (visit 1) and study end (visit 4) in a local laboratory. The laboratory values within 4 weeks prior to baseline (visit 1) will be allowed to use at study visit 1. The rescue medication is the IRcodon(R). Patients will be withdrawn from the study if the following circumstance require study drug discontinuation: Failure of pain control (Failure of pain control will be decided by investigators judgement, e.g. there is poor pain control or lack of efficacy despite 2 3 times of titration.) Adjustment of the other analgesics due to Adverse event except TARGIN(R) or IRcodon(R) Adjustment of the other major pain management modality (e.g. surgery, non-surgical interventional therapy, etc.) Withdrawal of informed consent Pregnancy Any other significant risk to the patient's safety in the clinical judgement of the investigator

Official Title
-----------------
A Multicenter, Phase IV, Interventional Study to Assess the Efficacy and Safety of TARGIN(R) (Oxycodone/Naloxone) in Korean Patients With Spinal Disorders

Conditions
-----------------
Spinal Disorders

Intervention / Treatment
-----------------
* Drug: Oxycodone/naloxone


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxycodone/Naloxone<br>Single-arm study | Drug: Oxycodone/naloxone<br>* Targin 5mg, 10mg, 20mg up to 40mg b.i.d<br>* Other names: Targin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pain Intensity of Patient With Spinal Disorder as Measured by NRS. | NRS-Pain scale assessed the severity of a subject's pain of mean pain over the past 24 hours prior to the visit on a scale of 0 (No pain) and 10 (Worst possible pain). Change = mean score at Week 8/ET minus mean score at Baseline. | Baseline, 8 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in Quality of Life (EQ-5D) at Week 8 of Treatment With the Study Drug From Baseline | EQ-5D to measure of health related quality of life should be answered as one of 3 levels about current condition for 5 dimensions and was calculated total average by giving a weighting on 3 level of answers (EQ-5D levels into 'no problems' (level 1) and 'problems' (level 2 and 3)). Table of scores by each level for EQ-5D items: mobility(level 1=0, level2=0.069,level 3=0.314), self care(level 1=0, level2=0.104,level 3=0.214), usual activities(level 1=0, level2=0.036,level 3=0.094), pain/discomfort (level 1=0, level2=0.,level 3=0.386) and anxiety/depression(level 1=0, level2=0.071,level 3=0.2) *EQ-5D Total = 1 - 0.081 - (the score of the each level) - 0.269 (if at least one of level 3 presents) EQ-5D total score could be 0.919 in maximum and -0.594 in minimum if case all index indicates the level 3. So, if EQ-5D total score closed by 1 means that the healthy condition and high quality of life. | Baseline, 8 week | 
| Clinical Global Impression of Change(CGIC) | The number of patients who choose the best opinion of overall satisfaction among Clinical Global Impression of Change Scale(CGIC) among 7 point scale. Missing data was imputed by LOCF. Very much improved much improved minimally improved no change minimally worse much worse very much worse | Baseline, 8 week | 
| Change of Pain Intensity in Patient With Spinal Disorder at Week 4 of Treatment With the Study Drug From Baseline | NRS-Pain scale assessed the severity of a subject's pain of mean pain over the past 24 hours prior to the visit on a scale of 0 (No pain) and 10 (Worst possible pain). Change = mean score at Week 4/ET minus mean score at Baseline. | Baseline, 4 week | 
| Change From Baseline in Health-related Quality of Life Assessed by EuroQol Visual Analog Scale (EQ-5D VAS) | The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' (score = 100) and 'Worst imaginable health state' (score = 0). Higher points were positive results and positive points of difference gap means improvement results. | Baseline, 8 weeks | 
| Patient Global Impression of Change(PGIC) | Number of participants with categorical change in overall satisfaction. PGIC: a participant-rated instrument assessing change in participant's overall satisfaction from baseline, on a scale ranging from 1 (very much improved) to 7 (very much worse). | Baseline, 8week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
spinal disorders