A Phase III, Randomized, Double-blind, Double-dummy, Parallel Group Study to Determine the Safety and Efficacy of Oxycodone / Naloxone Prolonged Release Tablets 5/2.5mg, 10/5mg, 20/10mg or 40/20mg Compared to Oxycodone PR 5mg, 10mg, 20mg or 40mg in Subjects With Moderate to Severe, Chronic Cancer Pain
1. Males & females, at least 18 years or older with a diagnosis of cancer.
2. 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.
3. 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.
4. 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.
5. Opioid medication continue at a stable or nearly stable dose in the investigator's
opinion during the treatment.
6. Subjects are willing to discontinue pre study laxative medication & take study
specific laxative medication.
7. 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.
8. 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
9. 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.
10. Expected survival time > 3 months.
11. With capability of reading, understanding & signing inform consent form & compliance
with protocol requirements.
1. Subjects that require a dose >80 mg/day oxycodone PR at the start of the double-blind
2. Any history of hypersensitivity to oxycodone, naloxone, morphine, bisacodyl, related
products & other ingredients.
3. 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.
4. 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.
5. 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
6. 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).
7. 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
8. Radiotherapy that, in the investigators opinion, would influence bowel function or
pain during the double-blind phase of the study.
9. 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.
10. Subjects with uncontrolled seizures.
11. Subjects with increased intracranial pressure.
12. 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.
13. Subjects with myxoedema, not adequately treated hypothyroidism or Addisons disease.
14. Subjects who have a confirmed diagnosis of ongoing irritable bowel syndrome(IBS).
15. 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.
16. Subjects receiving opioid substitution therapy for opioid addiction (e.g. methadone
17. Active alcohol or drug abuse & or history of opioid abuse.
18. Subjects suffering from diarrhoea & or opioid withdrawal.
19. Subjects presently taking, or who have taken, naloxone ≤30 days prior to the start of
the Screening Period.
20. 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