The Purpose of this study is to determine whether CG5503 is effective and safe in the treatment of chronic tumor related pain compared to placebo. In addition CG5503 will also be compared to morphine SR.

Normally chronic tumor related pain is controlled when subjects receive repeated doses of opioid analgesics. However, opioid therapy is commonly associated with side effects such as nausea, vomiting, sedation, constipation, addiction, tolerance, and respiratory depression. CG5503, a newly synthesized drug with an prolonged release (PR) formulation, also acts as a centrally acting pain reliever but has a dual mode of action. The aim of this trial is to investigate the effectiveness (level of pain control) and safety (side effects) of CG5503 PR compared with no drug (placebo) and corresponding dose of morphine (an opioid commonly used to treat tumor related pain). This trial is a randomized, double-blind (neither investigator nor patient will know which treatment was received), active- and placebo-controlled, parallel-group, multicenter trial.

The trial includes a 2 week titration phase starting with either 40 mg morphine (PR) bid or 100 mg CG5503 PR bid. Based on effectiveness and side effects subjects can up-titrate in steps of 50 mg CG5503 PR (20 mg morphine PR) to a maximal dose of 250 mg CG5503 PR bid or 100 mg morphine PR bid. If subjects meet the stabilisation criteria at the end of the titration phase they will be re-randomized to either placebo or active treatment and will continue 4 weeks at the last dose level in the maintenance phase.

Assessments of pain relief include the pain intensity numeric rating scale (NRS), patient global impression of change scale (PGIC). Safety evaluations include monitoring of adverse events, physical examinations, and clinical laboratory tests. Venous blood samples will be collected for the determination of serum concentrations of CG5503

• Tumor
• Pain

• Drug: CG5503 ER
  Tablet taken orally, twice daily, morning & evening with preferably 12 hrs (not less than 6 hrs) between doses. Titration phase: Starting at 100 mg, increasing at a minimum of 3 day intervals by 50 mg, with a maximum dose of 250 mg. Maintenance phase: continuing on dose level established in titration phase.
• Drug: Placebo to match CG5503
  Tablet taken orally, twice daily, morning & evening with preferably 12 hrs (not less than 6 hrs) between doses
• Drug: Morphine Sulphate CR
  Capsule taken orally, twice daily, morning & evening with preferably 12 hrs (not less than 6 hrs) between doses. Titration phase: Starting at 40 mg, increasing at a minimum of 3 days intervals by 20 mg, with a maximum dose of 100 mg. Maintenance phase: continuing on dose level established in titration phase.
• Drug: Placebo to match Morphine Sulphate CR
  Capsule taken orally, twice daily, morning & evening with preferably 12 hrs (not less than 6 hrs) between doses

• A: Experimental
  Entering the titration phase subjects will be randomized into either ARM A or ARM C, with a ratio of 2:1 respectively. In the maintenance phase subjects in ARM A will be re-randomized into either ARM A or ARM B, with a ratio of 1:1.
  Interventions:

  • Drug: CG5503 ER
  • Drug: Placebo to match Morphine Sulphate CR
• B: Placebo Comparator
  In the maintenance phase subjects in ARM A will be re-randomized into either ARM A or ARM B with a ratio of 1:1.
  Interventions:

  • Drug: Placebo to match CG5503
  • Drug: Placebo to match Morphine Sulphate CR
• C: Active Comparator
  Entering the titration phase subjects will be randomized into either ARM A or ARM B, with a ratio of 2:1 respectively. In the maintenance phase subjects in ARM C will continue in ARM C
  Interventions:

  • Drug: Placebo to match CG5503
  • Drug: Morphine Sulphate CR

Inclusion Criteria

• Male and non-pregnant, non-lactating female subjects.
• Of at least 18 years of age with chronic malignant tumor-related pain with a mean pain intensity (NRS) of 5 points or higher.
• Subjects who are opioid-naïve or pretreated with an equianalgesic dose range equivalent of up to 160 mg oral morphine per day and are dissatisfied with prior treatment.
• Women must be postmenopausal, surgically sterile, or practicing or agree to practice an effective method of birth control throughout the trial.

Exclusion Criteria

Key Exclusion Criteria:

• Subjects will be excluded from the study if they have a history of seizure disorder or epilepsy;
• cerebral metastases;
• history of alcohol or drug abuse;
• uncontrolled hypertension,
• clinical laboratory values reflecting severe renal insufficiency,
• moderate or severe hepatic impairment,
• hepatitis B or C, HIV,
• thrombopenia, leukopenia or hypercalcemia,
• currently treated with radiotherapy,
• pain inducing chemotherapy,
• anti-parkinsonian drugs, neuroleptics, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitor (SNRI) or any other analgesic therapy than investigational medication or rescue medication during the trial.
• selective serotonin reuptake inhibitor (SSRI) treatments are allowed if taken for at least 30 days before the screening period of the study at an unchanged dose.