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
Information obtained from ClinicalTrials.gov on June 20, 2008
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 Corporation, DE, USA
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: Treatment, Non-Randomized, Open Label, Single Group Assignment, Pharmacokinetics Study
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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Ending date: August 1999
Last updated: April 17, 2008