Trial Information

A Randomized, Double-Blind, Controlled Trial of Hydromorphone (Immediate and Sustained- Release) vs Morphine (Immediate and Sustained-release) in Cancer Pain

This was a phase-3, multicenter, multinational, randomized (patients are assigned different
treatments based on chance), active-controlled, double-blind, multiple-ascending-dose,
parallel-group study in adult patients with cancer pain who receive and/or require strong
oral or transdermal opioid analgesics (60-540 mg of oral morphine equivalents daily). This
study consisted of 2 phases: an initial immediate release (IR) phase and a subsequent slow
release (SR) phase. Eligible patients were randomized 1:1 to receive either OROS
hydromorphone HCl or morphine sulfate (immediate release formulation in the immediate
release phase, slow release formulation in the slow release phase). In the immediate release
phase (2-9 days), patients were started on the appropriate initial dose of immediate release
medication every 4 hours (q4h), (6 doses/day) using a 5:1 conversion ratio (morphine
equivalents:hydromorphone dosage). If the patient had greater than 3 breakthrough-pain
episodes requiring additional pain medication in 24 hours, the study medication dosage was
increased, at most once a day. When the patient had achieved dose-stable pain control (2
days with 3 or less than 3 breakthrough-pain episodes per day), the patient was permitted
to continue into the slow release phase. The patient was given an equivalent dosage of a
slow release formulation of the same drug (OROS® hydromorphone HCL each day or morphine
sulfate slow release two times per day), administered using a double-dummy technique. Dosage
increases were permitted every 2 days if the patient had more than 3 breakthrough-pain
episodes in 24 hours. To complete the slow release phase, patients had to achieve
dose-stable pain control for at least 2 days.Safety assessments of physical examination,
labs and adverse event reporting were done. OROS hydromorphone HCL slow release 8, 16, 32,
and 64mg tablets; Morphine sulfate immediate release10, 20, 50 mg capsules;Morphine
sulfate slow release 5, 30, 60, 90, 120, 160, and 200mg capsules;hydromorphone immediate
release 2, 4, 8 mg;The immediate release medications orally every 4 hours;The OROS
hydromorphone slow release formulation orally every 24 hours and morphine slow release
orally twice daily.