A Study to Evaluate Efficacy and Safety of Oxycodone/Naloxone Compared to OxyContin in Korean Cancer Patients (TOP)

Objectives:

To prove non-inferiority of Targin compared to Oxycontin in terms of reduction of pain intensity

1. Primary objective: Actual reduction of pain intensity (0-10) score (average pain over 24 hours obtained each evening) within 4 weeks
2. Secondary objectives: Bowel Habit (worsening/no change/improving), Total dose and frequency of rescue medication, Quality of Life (QOL; EORTC QLQ-C30), Duration to need of laxative use and Adverse events, Long term safety and efficacy

This will be a 4-week multicentre, randomized, open label, parallel group, active control study to evaluate efficacy and safety of Targin in comparison with Oxycontin in Korean patients with cancer pain who are administered weak opioid or naïve patients including patient not on the long term strong opioid medication within 3 months.

• Experimental: Oxycodone and Naloxone
  Daily dose can be titrated up to 40mg B.I.D.
  Intervention: Drug: oxycodone and naloxone
• Active Comparator: Oxycodone
  Intervention: Drug: oxycodone and naloxone

Inclusion Criteria:

1. Male or female cancer patients 20 years of age or older
2. Cancer related pain that requires treatment with continuous around-the-clock strong opioid analgesic
3. Moderate to severe pain intensity(NRS pain score 4)
4. Opioid naïve patients or patients not treated with strong opioids(except PRN) within 4 weeks or patients who has been on weak opioids
5. Subject who provide signed and dated written voluntary informed consent

Exclusion Criteria:

1. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. UNLESS they are:

   • women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner
   • women shoes partners have been sterilized by vasectomy or other means
   • two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent.
2. 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.
3. Have previously received treatment with Targin or Oxycontin within 4weeks(28days) of screening periods(including PRN)

4. If subjects started first cycle of chemotherapy during the 2 weeks before the screening visit or during the study, they should be excluded from the study.

   And If the chemotherapy regimen or dosage to be planned to change during the study, the subjects should be excluded from the study.

5. Patient who is administered laxatives with stable dose for more than 1 week
6. Patient with evidence of significant structural/functional abnormalities of GI tract which is not appropriate for oral medicine administration. Any history of hypersensitivity to Oxycodone and Naloxone
7. Patients with significant respiratory depression
8. Patients with acute or severe bronchial asthma or hypercarbia
9. Any patient who has or is suspected of having paralytic ileus
10. Severe Chronic obstructive pulmonary disease, pulmonary heart disease
11. Targin product contains lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take
12. Patients with moderate and severe hepatic impairment
13. 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)
14. Any situation where opioids are contraindicated
15. Major surgery within 1 month prior to screening or planned surgery
16. Mainly pain originated other than cancer or cancer related conditions (eg. Musculoskeletal pain, inflammatory pain, diabetic polyneuropathy)
17. Patients with known or suspected unstable brain metastases or spinal cord compression that may require changes in steroid treatment throughout the duration of the study
18. Patients with uncontrolled seizures
19. Requiring interventional treatment for pain such as neurodestructive procedure or regional infusion
20. With a history of alcohol abuse within 6 months of screening
21. With a history of illicit drug abuse within 6 months of screening
22. Patients with increased intracranial pressure
23. In the investigator's opinion, subjects who are receiving hypnotics or other central nervous system (CNS) depressants that may pose a risk of additional CNS depression with opioid study medication
24. Patients with myxodema, not adequately treated hypothyroidism or Addison's disease
25. Patients receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine)
26. Patients with evidence of clinically significant gastrointestinal disease (e.g. paralytic ileus, peritoneal carcinosis), significant structural abnormalities of the gastrointestinal tract (e.g. scarring, obstruction etc) either related or not related to the underlying cancer or disease progression
27. Patients suffering from diarrhea and/or opioid withdrawal
28. With a disability that may prevent the patient from completing all study requirements and in particular, interfere with 24hrs pain intensity score
29. Clinically significant impairment of cardiovascular, respiratory and renal function
30. Patient who needs acute dose titration or whose pain intensity fluctuate significantly in a short period according to investigator's judgment
31. Having used other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer