A Repeated Dose Study of the Metabolism and Action Evaluation of OROS Hydromorphone HCI (Slow Release) Tablets in Patients With Chronic Pain
Condition: Pain; Analgesics, Opioid
MeSH terms: Chronic Pain
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): OROS Hydromorphone HCI (slow release)
Intervention type(s): Drug
Intervention MeSH terms: Hydromorphone
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Opioids; Chronic cancer pain; Analgesic