A Repeated Dose Study of the Metabolism and Action Evaluation of OROS Hydromorphone HCI (Slow Release) Tablets in Patients With Chronic Pain
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 HCI (slow release) (Drug)
Phase: Phase 1
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 characterize the steady-state pharmacokinetic (metabolism
and action) profile of OROS hydromorphone HCI (slow release) in patients who required opioid
therapy on a daily basis for chronic pain conditions. Patients stabilized on prior opioids
were converted to OROS hydromorphone slow release and titrated (slowly increased or
decreased) to adequate analgesia (pain relief). They were maintained at that dose for 4-10
days and had blood samples drawn over 24 hours on the last day of study.
Official title: A Repeated-Dose Pharmacokinetic Evaluation of Dilaudid SR Tablets (Hydromorphone HCI) in Patients With Chronic Pain
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The pharmacokinetic (absorption, distribution, excretion) profile of OROS hydromorphone. The time required for absorption and distribution in the body.
Secondary outcome: Relationships between pharmacokinetic (absorption, distribution, excretion) and pharmacodynamic (drug action on body systems) responses. Patients rated their pain intensity prior to each time blood was draw.
This was an open-label, repeated-dose study involving patients who required opioid therapy
on a daily basis for chronic pain conditions. In this study, baseline evaluations were
performed at Visit 1. Patients were given a diary in which to record daily opioid
medication use and daily pain-relief ratings throughout the study. During the time between
Visit 1 and Visit 2 patients continued taking their prior oral or transdermal opioid
medication for pain. Patients were considered stabilized when during usual activity, the
total daily dose of baseline medication remained unchanged, with no more than three opioid
breakthrough pain medication doses/day administered, for two consecutive days. Patients
returned within 1 week of Visit 1 for Visit 2. During this visit, patient's 24-hour
baseline oral opioid dose was converted to hydromorphone at a conversion ratio of
approximately 5: 1 (oral morphine sulfate to oral hydromorphone HCI mg equivalents).
Patients were dispensed OROS hydromorphone HCI slow release tablets and were then increased
to acceptable analgesia (pain relief). Eligible stabilized patients requiring a total daily
dose of at least 8 mg but no more than 64 mg of OROS hydromorphone HCI slow release
(exclusive of breakthrough medication) began the 5-10 day maintenance therapy phase at Visit
3. Morphine sulfate (immediate-release tablets) were provided as breakthrough pain
medication. Patients returned to the clinic in the morning following a minimum of 4 days of
continuous OROS hydromorphone HCI slow release therapy at a constant daily dose for Visit 4.
Upon arrival at the clinic, an initial (trough) blood sample was taken prior to witnessed
administration of the usual dosage of OROS hydromorphone HCI slow release. The exact time
of the drug administration was documented. Patients were instructed to return the following
morning and not to consume food or beverage within 3 hours of their scheduled visit.
Patients were instructed not to self administer their OROS hydromorphone HCI slow release
the following morning; they were dosed in the clinic. Patients could take immediate release
morphine sulfate as needed. Patients returned to the clinic the next morning (visit 5) and
remained for a 24-hour period for witnessed dosing and plasma (blood) sampling for
pharmacokinetic (metabolism/action) analysis. Dosing and plasma (blood) sampling began 24
hours following the time of dosing at the clinic the previous day. Water (240 mL) was taken
with the medication. Immediately prior to each blood draw, patients rated their pain
intensity using an 11-point scale and rated their pain intensity from 0 (no pain) to 10
(pain as bad as you can imagine). Blood samples for analysis were drawn at: 0 (prior to
dosing), 1,2,4,6,8,10,12,15,18,21 and 24 hours after dosing. Urine output was collected
over the 24-hour period from selected patients. Vital signs were taken. At the conclusion
of Visit 5 or in the event of early study termination, a Global Evaluation and physical
examination were performed. The patient's diary was reviewed with the patient and all
unused study medication was collected. Safety assessments included vital signs and physical
examination at the start and end of study. OROS Hydromorphone HCL (slow release) 8,16,32,and
64 mg tablets orally. Patients were stabilized on prior opioids then converted to OROS
Hydromorphone HCL (slow release) and slowly increased or decreased to adequate analgesia.
Then the patients were maintained at that dose for 4 - 10 days. Duration of treatment was
up to 31 days.
Minimum age: 18 Years.
Maximum age: N/A.
- Patients who had chronic nonmalignant or chronic cancer pain and were currently
receiving strong oral or transdermal opioid analgesics (drug that relieves pain) on a
daily basis or patients suitable for advancement of therapy to step 3 on the WHO
(World Health Organization) analgesic (drug that relieves pain) ladder
- Patients who required the opioid equivalent of at least 32 mg but no more than 300 mg
of oral morphine sulfate or opioid equivalent (exclusive of breakthrough pain
medication) every 24 hours for the management of chronic nonmalignant or cancer pain
- Patients who were expected to have reasonably stable opioid requirements for the
duration of the study
- Patients intolerant of or hypersensitive to hydromorphone (or other opioid drugs)
- Patients who were pregnant or breast-feeding. Patients with any dysphagia or unable to
swallow tablets, acute abdominal conditions that may be obscured by opioids or
gastrointestinal disorders, including pre-existing severe GI narrowing, that may
affect the absorption or transit of orally administered drugs
- Patients with any significant CNS disorder, including but not limited to head injury,
intracranial lesion, increased intracranial pressure, seizure disorder, stroke within
the past 6 months, and disorders of cognition, and clinically significant impaired
- Patients that may be at risk for serious decreases in blood pressure following
administration of an opioid analgesic (pain relief)
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