Determine the Safety and Efficacy of Oxy/Nal Tablets Compared to Oxy PR in Subjects With Cancer Pain
Condition: Cancer; Pain
MeSH terms: Cancer Pain
Intervention: Oxycodone/Naloxone; Oxycodone
Intervention MeSH terms: Oxycodone; Naloxone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 232.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

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.