Clinical trial NCT00505414
Conditions: Pain Neoplasm Cancer
Keywords: Chronic Tumor Related Pain Analgesic Tapentadol Extended Release Morphine Sulfate Controlled Release Pain assessment Placebo
Sponsor: Grünenthal GmbH
Start date: 2007-06-01; Completion date: 2009-05-01
Enrollment: 136 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether CG5503 (tapentadol) is effective and safe in the treatment of chronic tumor related pain compared to placebo.

Detailed description:
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. Tapentadol, a newly synthesized drug with an Prolonged Release (ER) 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 Tapentadol Prolonged Release (ER) compared to a tablet with no active ingredient drug (placebo) and a 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, randomized-withdrawal, multicenter trial. To maintain the blind all subjects were re-randomized at the start of the maintenance period. To maintain the blind all tapentadol subjects were re-randomized at the start of the maintenance period. Subjects that received morphine in the titration period continued in the maintenance period on morphine.

The trial includes a 2 week titration phase starting with either 45 mg Morphine Sulfate Controlled Release (CR) twice daily or 100 mg tapentadol ER taken twice daily (bid). Based on effectiveness and side effects participants can up-titrate in steps of 50 mg Tapentadol ER or 15 mg Morphine Sulfate CR to a maximal dose of 250 mg Tapentadol ER bid or 90 mg Morphine Sulfate CR twice daily respectively. If subjects meet the stabilization 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, defined as a responder include the pain intensity numeric rating scale (NRS). The Patient Global Impression of Change scale (PGIC) will also be used as a secondary efficacy endpoint. 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 tapentadol.

Arms: arm 1: Oral Tapentadol 100 mg to 250 mg twice daily. Followed by matching placebo in the maintenance (i.e. randomized withdrawal phase). arm 2: Oral Morphine 45 mg to 90 mg twice daily. arm 3: Oral Tapentadol 100 mg to 250 mg twice daily.
Interventions: intervention 1: Tapentadol in the Titration Phase intervention 2: Morphine in the Maintenance Phase intervention 3: Matching Placebo in the Maintenance Phase after Tapentadol in the Titration Phase intervention 4: Tapentadol in the Maintenance Phase intervention 5: Morphine in the Titration Phase
Intervention descriptions: intervention 1: None intervention 2: Participant started the trials with 45 mg morphine controlled release twice daily. Upward titration could then occur at a minimum of 3-day intervals in increments of 15 mg morphine twice daily. The maximum dose of morphine controlled release was 90 mg twice daily. Downward titration (but not below 45 mg twice daily) was permitted. In the maintenance phase participants continued on the dose level established in titration phase.

Participants randomized to the morphine arm remained on morphine if they qualified for the maintenance phase of the study. The participants were maintained on the dose established at the end of the titration phase. The adverse events listed were documented in the maintenance phase. intervention 3: Participant randomized to placebo in the maintenance phase received 100 mg tapentadol prolonged release twice daily for 3 days to taper them off of the tapentadol dose they had received in the titration period. From the fourth day of the maintenance period onwards they received placebo twice daily. intervention 4: The participants re-randomized to receive tapentadol prolonged release in the maintenance phase were maintained on the dose established in the titration phase. intervention 5: After signing informed consent eligible subjects were randomized to receive morphine controlled release. The oral medication was taken twice daily, morning and evening every 12 hours (with a minimum of 6 hours between doses). Participant started the trials with 45 mg morphine controlled release twice daily. Upward titration could then occur at a minimum of 3-day intervals in increments of 15 mg morphine twice daily. The maximum dose of morphine controlled release was 90 mg twice daily. Downward titration (but not below 45 mg twice daily) was permitted.

Protocol documents: