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

Phase 3
18 Years
Not Enrolling
Pain, Analgesics, Opioid

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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 (OROSĀ® 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.

Inclusion Criteria:

- Patients with cancer pain who are currently receiving strong oral or transdermal
opioid analgesics or in whom strong opioid analgesics are appropriate

- Patients who requires or are expected to require between 60 and 540 mg of oral
morphine or morphine equivalents every 24 hours for the chronic management of cancer

- Patients who have pain suitable for treatment with a once-daily formulation

- Patients with concomitant chemotherapy or radiotherapy. Exclusion Criteria:

- Patient with gastrointestinal (GI) disease of sufficient severity to interfere with
orally administered analgesia (eg dysphagia, vomiting, constipation, bowel
obstruction, severe gut narrowing) were not permitted to enroll

- Patient where the risks of treatment with morphine or hydromorphone outweighed the
potential benefits such as raised intracranial pressure, hypotension, hypothyroidism,
asthma, reduced respiratory reserve, prostatic hypertrophy, hepatic or renal
impairment, convulsive disorders, and Addison's disease

- Debilitated patients were excluded.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:

The primary efficacy : Patient's assessment of "worst pain in the past 24 hours" Brief Pain Inventory (BPI) questions, scored daily in the patient's diary.

Principal Investigator

Alza Corporation Clinical Trial

Investigator Role:

Study Director

Investigator Affiliation:



United States: Institutional Review Board

Study ID:




Start Date:

Completion Date:

May 2001

Related Keywords:

  • Pain
  • Analgesics, Opioid
  • Cancer pain
  • Oral analgesic
  • OROS hydromorphone HCL
  • Morphine sulfate