Determine the Safety and Efficacy of Oxy/Nal Tablets Compared to Oxy PR in Subjects With Cancer Pain

To Determine the Safety and Efficacy of Oxycodone / Naloxone Prolonged Release Tablets compared to Oxycodone PR in Subjects with Moderate to Severe, Chronic Cancer Pain

This is a randomised, double-blind, double-dummy, parallel group study using OXN and OXY PR to treat moderate to severe, chronic cancer pain. Subjects with documented history of cancer pain that requires around the clock opioid therapy will be included. Subjects must have a medical history of constipation that was induced by, or worsened by their opioid therapy.

Eligibility Criteria:
Inclusion Criteria

Males \& females, at least 18 years or older with a diagnosis of cancer.

Females less than one year post-menopausal must have a negative urine pregnancy test recorded prior to the first dose of study medication, be non-lactating, \& willing to use adequate \& highly effective method of contraception throughout the study. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (hormonal), sexual abstinence or vasectomised partner.

Subjects who are receiving WHO step II or Step III analgesic medication who have constipation induced, or worsened by their opioid medication, as shown by

1. the subject's medical need of regular intake of laxatives to have at least 3 bowel evacuations per week, or having less than 3 bowel evacuations when not taking a laxative, respectively.
2. the subject's self-assessment that their constipation was induced or worsened by their current pre-study opioid medication.

Documented history of moderate to severe, chronic cancer pain that requires around the-clock opioid therapy (starting dose of oxycodone PR between 20-80 mg/day) \& are likely to benefit from WHO step III opioid therapy for the duration of the study. Subjects must be willing to discontinue their current opioid analgesic routine.

Opioid medication continue at a stable or nearly stable dose in the investigator's opinion during the treatment.

Subjects are willing to discontinue pre study laxative medication \& take study specific laxative medication.

Subjects taking daily fibre supplementation or bulking agents are eligible if they can be maintained on a stable dose \& regimen throughout the study, \& in the investigators opinion are willing \& able to maintain adequate hydration.

Subjects willing \& able (e.g. mental \& physical condition) to participate in all aspects of the study, including use of medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts, \& compliance with protocol requirements as evidenced by providing written, informed consent.

Subjects already taking non-opioid analgesics \& all other concomitant medications (including those for the treatment of depression) are eligible to take part in the study. However, all concomitant medications that are considered necessary for the subject's welfare should be continued at a stable dose throughout the double-blind phase of the study \& under the supervision of the investigator.

Expected survival time \> 3 months.

With capability of reading, understanding \& signing inform consent form \& compliance with protocol requirements.

Exclusion Criteria Subjects that require a dose \>80 mg/day oxycodone PR at the start of the double-blind phase.

Any history of hypersensitivity to oxycodone, naloxone, morphine, bisacodyl, related products \& other ingredients.

Subjects with any situation in which opioids are contra-indicated, severe respiratory depression with hypoxia \& or hypercapnia, severe chronic obstructive pulmonary disease, cor pulmonal, severe bronchial asthma, paralytic ileus.

Subjects 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.

Evidence of clinically significant cardiovascular, renal, hepatic or psychiatric disease, as determined by medical history, clinical laboratory tests, ECG results \& physical examination, that would place the subject at risk upon exposure to the study medication or that may confound the analysis \& or interpretation of the study results.

Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), r-glutamyltransferase (GGT) or alkaline phosphatase levels (\>3 times the upper limit of normal) or an abnormal total bilirubin \& or creatinine level(s) (greater than 1.5 times the upper limit of normal).

Cyclic chemotherapy in the two weeks before the screening visit or planned during the core study that has shown in the past to influence bowel function. If subjects are having their first cycle of chemotherapy during the 2 weeks before the screening visit or during the double-blind phase of the study they should be excluded from the study.

Radiotherapy that, in the investigators opinion, would influence bowel function or pain during the double-blind phase of the study.

Subjects with known or suspected unstable brain metastases or spinal cord compression that may require changes in steroid treatment throughout the duration of the study.

Subjects with uncontrolled seizures.

Subjects with increased intracranial pressure.

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.

Subjects with myxoedema, not adequately treated hypothyroidism or Addisons disease.

Subjects who have a confirmed diagnosis of ongoing irritable bowel syndrome(IBS).

Surgery completed within 4 weeks prior to the start of the Screening Period, or planned surgery during the study that would influence pain or bowel function during the study or preclude completion of the study.

Subjects receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine).

Active alcohol or drug abuse \& or history of opioid abuse.

Subjects suffering from diarrhoea \& or opioid withdrawal.

Subjects presently taking, or who have taken, naloxone ≤30 days prior to the start of the Screening Period.

Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days of study entry (defined as the start of the Screening Period), unless the subject is on data collection phase for Overall Survival.