A Study of OROS Hydromorphone HCL vs Morphine in Cancer Pain Patients.
Information source: Alza Corporation, DE, USA
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pain; Analgesics, Opioid
Intervention: OROS hydromorphone HCL ; Morphine sulfate (Drug)
Phase: Phase 3
Sponsored by: Alza Corporation, DE, USA
Official(s) and/or principal investigator(s):
Alza Corporation Clinical Trial, Study Director, Affiliation: ALZA
The purpose of this study was to demonstrate the clinical equivalence of hydromorphone and
morphine (immediate-release [IR] and sustained-release [SR] formulations) using the "worst
pain in the past 24 hours" item of the Brief Pain Inventory (BPI). The secondary objective
of this study was to compare hydromorphone and morphine in the following variables: other
pain measures, various questionnaires, and safety and tolerability variables.
Official title: A Randomized, Double-Blind, Controlled Trial of Hydromorphone (Immediate and Sustained- Release) vs Morphine (Immediate and Sustained-release) in Cancer Pain
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Primary outcome: 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.
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.
Minimum age: 18 Years.
Maximum age: N/A.
- 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.
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