A Randomised, Double-blind, Active-controlled, Double-dummy, Parallel Group Study to Determine the Safety and Efficacy of Oxycodone/Naloxone Prolonged Release Tablets in Subjects With Moderate to Severe, Chronic Cancer Pain
1. Male or female subjects 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 at the screening visit, be non-lactating, and willing to use adequate and
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 and correctly such as
sterilization, 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 at the beginning of the double-blind
phase of oxycodone PR between 20 - 80 mg/day) and 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. Subjects are willing to discontinue pre-study laxative medication and take study
specific laxative medication.
6. Subjects taking daily fibre supplementation or bulking agents are eligible if they
can be maintained on a stable dose and regimen throughout the study, and in the
investigators opinion are willing and able to maintain adequate hydration.
7. Subjects willing and able (e.g. mental and 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, and
compliance with protocol requirements as evidenced by providing written, informed
8. Subjects already taking non-opioid analgesics and 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 and under the supervision of the investigator. Regarding cyclic
chemotherapy please see exclusion criteria list.
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, bisacodyl, related products,
and other ingredients.
3. Subjects with any situation in which opioids are contra-indicated, severe respiratory
depression with hypoxia and/or hypercapnia, severe chronic obstructive pulmonary
disease, cor pulmonale, severe bronchial asthma, paralytic ileus.
4. Evidence of clinically significant cardiovascular, renal, hepatic or psychiatric
disease, as determined by medical history, clinical laboratory tests, ECG results,
and physical examination, that would place the subject at risk upon exposure to the
study medication or that may confound the analysis and/or interpretation of the study
5. Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT;
SGPT), or alkaline phosphatase levels (>3 times the upper limit of normal) or an
abnormal total bilirubin and/or creatinine level(s) (greater than 1.5 times the upper
limit of normal).
6. 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.
7. Subjects with uncontrolled seizures.
8. Subjects with increased intracranial pressure.
9. 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.
10. Subjects with myxodema, not adequately treated hypothyroidism or Addisons disease.
11. Active alcohol or drug abuse and/or history of opioid abuse.
12. Subjects receiving opioid substitution therapy for opioid addiction (e.g. methadone
13. 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.
14. Subjects who have a confirmed diagnosis of ongoing irritable bowel syndrome.
15. Subjects suffering from diarrhea and/or opioid withdrawal.
16. Surgery completed 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.
17. 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
18. Radiotherapy that, in the investigators opinion, would influence bowel function or
pain during the double-blind phase of the study.
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).