Clinical trial NCT00513656 (phase 2, status: completed)
Conditions: cancer, pain, constipation
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2, N50.82, R07.2, R07.82, R10.13, R10.33, R14.1, R52, K59.00, K59.09, K59.01, K59.02, K59.03, K59.04, K58.1
Drugs: oxycodone, oxycodone/naloxone
SMILES: CC(=O)OC1=CC=CC=C1C(O)=O, OC1=CC=C2C[C@H]3N(CC=C)CC[C@@]45[C@@H](OC1=C24)C(=O)CC[C@@]35O
Eligibility criteria:

        Inclusion Criteria:

          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
             consent.

          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.

        Exclusion Criteria:

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

          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
             results.

          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 or
             buprenorphine).

         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 study.

         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).