Study of the Effectiveness and Tolerability of OROS Hydromorphone HCI SR(Slow-release) Tablets and Immediate-Release Hydromorphone Tablets in Patients With Chronic Pain

Last updated: April 26, 2010
Sponsor: Alza Corporation, DE, USA
Overall Status: Completed

Phase

3

Condition

Pain

Chronic Pain

Treatment

N/A

Clinical Study ID

NCT00410943
CR013276
  • Ages > 18
  • All Genders

Study Summary

The purpose of this study was to characterize a safe and effective means of conversion and titration to an appropriate dose of hydromorphone HCI, to demonstrate comparable efficacy of OROS hydromorphone HCI SR (slow release) and hydromorphone HCI IR (immediate release) following administration of approximately equivalent total daily doses and demonstrate a significant dose-response relationship between OROS hydromorphone HCI SR (slow release) for breakthrough pain medication use or alternatively, diary-based analgesic scores

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Patients who have chronic non-malignant or cancer pain currently receiving strong ortransdermal opioid analgesics on a daily basis or patients suitable for advancement oftherapy to step 3 on the WHO (World Health Organization) analgesic ladder

  • Patients who, at Visit 2, require the equivalent of at least 80 mg but no more than 300 mg of oral morphine sulfate (exclusive of breakthrough pain medication) every 24hours or at least 25 micrograms an hour but no more than 75 micrograms an hour ofFentanyl

  • Patients must be on a stable dose of a strong opioid medication at Visit 2. Patientswill be considered stabilized when the total daily dose of their prestudy opioidmedication remains unchanged, with no more than three opioid breakthrough paindoses/day administered for breakthrough pain, for two consecutive days

  • Patients who can be expected to have reasonably stable opioid requirements for theduration of the study

Exclusion

Exclusion Criteria:

  • Patients intolerant of or hypersensitive to hydromorphone (or other opioid agonists)

  • Patients who have difficulty swallowing or are unable to swallow tablets

  • Patients who are pregnant or breast-feeding. Female patients of child-bearingpotential must be following a medically recognized contraceptive program prior to andduring the study. A negative pregnancy test is required prior to administration ofstudy drug

  • Patients with any gastrointestinal disorder, including pre-existing severegastrointestinal narrowing that may affect the absorption or transit of orallyadministered drugs

  • Patients with any intracranial lesion, increased intracranial pressure, seizuredisorder, stroke within the past 6 months, and disorders of cognition

  • Patients with clinically significant impaired kidney or liver function, thyroiddisease, enlarged prostate, or urethral narrowing

  • Patients who may be at risk for serious decreases in blood pressure uponadministration of an opioid analgesic

Study Design

Total Participants: 169
Study Start date:
Estimated Completion Date:
June 30, 1999

Study Description

This was a randomized (patients are assigned different treatments based on chance), double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), repeated-dose, three-arm parallel group study conducted in three phases. Following a Prior Opioid Stabilization Phase, wherein patients were required to be on a stable dose of chronic opioid therapy, patients were converted, titrated and stabilized on hydromorphone HCI IR (immediate release) to achieve acceptable levels of analgesia in the Open-Label Hydromorphone HCI IR (immediate release) Conversion, Titration, and Stabilization Phase. Supplementary hydromorphone HCI IR (immediate release) was provided for breakthrough pain, and patients were considered stabilized on hydromorphone HCI IR (immediate release) when the total daily dose of hydromorphone HCI IR (immediate release) remained unchanged with no more than three hydromorphone HCI IR (immediate release) breakthrough pain medication doses per day for 2 consecutive days. Patients who were able to achieve a stable total daily dose of at least 20 mg but not more than 60 mg of hydromorphone HCI IR (immediate release) (exclusive of breakthrough pain medication) within the 14 day Open-Label hydromorphone HCI IR (immediate release) Conversion, Titration, and Stabilization Phase of the study entered the Double-Blind, Randomized, Repeat Dosing Phase of the study. Patients were randomized to receive 7 days of either OROS hydromorphone HCI SR (slow release) at a daily dose approximately equal to their stabilized total daily dose of hydromorphone HCI IR (immediate release), OROS hydromorphone HCI SR (slow release) at a daily dose approximately equal to one-half their stabilized total daily dose of hydromorphone HCI IR (immediate release) (1/2 OROS hydromorphone slow release), or hydromorphone HCI IR (immediate release) at the same daily dose on which they were stabilized (hydromorphone immediate release). Patients who completed the study were eligible for participation in an open-label OROS hydromorphone SR (slow release) long-term extension study (Protocol DO-109). OROS hydromorphone slow release 8, 16 and 32 mg tablets, hydromorphone immediate release 2 and 4 mg tablets, placebo immediate release 2 and 4 mg tablets and placebo slow release 8, 16, and 32 mg tablets taken orally for 7 days