A Phase III Double-Blind Equivalence Study of Two Different Formulations of Slow-Release Morphine Followed by a Randomization Between Dextromethorphan or Placebo Plus Statex SR for Chronic Cancer Pain Relief in Terminally Ill Patients

OBJECTIVES:

• Compare the analgesic efficacy of two formulations of morphine (Statex SR versus MS-Contin) in patients requiring morphine for the treatment of chronic cancer pain.
• Compare the effect of these 2 formulations of morphine on the total analgesic consumption, sleep disturbances, sleep and nausea, responses of different types of pain, and toxic effects experienced in the two treatment groups.
• Compare the effect of coadministration of morphine and dextromethorphan versus morphine and placebo on pain control in the respective patient groups (phase B).
• Compare the effect of morphine and dextromethorphan or placebo on total analgesic consumption, sleep disturbances, sleep and nausea, responses of different types of pain, and toxic effects on the two treatment groups (phase B).

OUTLINE: This is a randomized, double-blind, parallel-group, multicenter study. Patients are stratified by stabilization dose (less than 120 mg/day vs greater than 120 mg/day of morphine) and institution in phase A, and neuropathic pain (yes vs no) in phase B.

• Phase A: Patients are randomized to receive oral morphine in one of two formulations (MS Contin or Statex SR) every 12 hours for 7 days.
• Phase B: Eligible patients from phase A who have taken no more than 2 breakthrough doses of analgesic per day in the previous 2 days are re-randomized to receive dose escalated oral dextromethorphan capsules or placebo every 4 hours, and oral morphine tablets every 12 hours for 14 days.
• Phase C: All patients fulfilling entry criteria at the end of phase A or any time during phase B may receive compassionate use morphine tablets for up to 90 days.

Patients complete a pain diary twice each day during treatment.