An Open-Label Evaluation of the Dose Proportionality of OROS� Hydromorphone HCL Tablets 8mg, 16mg, 32mg, 64mg
Summary
The primary objective of this study was to examine the OROS® Hydromorphone HCL pharmacokinetic (the way a drug enters and leaves the blood and tissues over time) profile for dose proportionality after administration of 8mg, 16mg, 32mg and 64 mg tablets.
Description
This was a randomized (patients are assigned different treatments based on chance), open-label, four-way crossover study performed in normal, healthy adult patients. Each patient received the following orally administered treatments of OROS® Hydromorphone HCL (a different treatment during each dosing phase): Treatment A: 8mg; Treatment B: 16mg; Treatment C: 32mg; Treatment D: 64mg; A naltrexone 50mg dose was administered 12 hours prior to, at the time of, and 12 after study drug administration; Patients received a fourth dose of naltrexone 50mg 24 hours after the 64mg study drug administration. There was a 7-day washout period between study drug dosing phases.Venous blood sampling times were 0 (prior to dosing), 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 hours after each study drug administration. Three additional blood samples (at 56, 64, and 72 hours after dosing of study drug) were drawn from those patients receiving the 64 mg tablets; LC/MS/MS (Liquid Chromatography/Mass Spectroscopy/Mass Spectroscopy) techniques were employed for the analysis of plasma hydromorphone concentrations.The primary endpoints of interest were: Area under the concentration-time curve from zero to infinity; Area under the concentration-time curve from zero to time t; Peak plasma concentration; the secondary endpoint parameters were: Time to peak plasma concentration; Terminal half-life. OROS hydromorphone HCL tablets of 8mg, 16mg, 32mg, and 64mg were given orally, a different dosing treatment during each dosing phase. One naltrexone HCL 50mg tablet was given orally 12 hours prior to, at the time of, and 12 hours after hydromorphone administration during each dosing phase. Patient received a fourth dose of naltrexone 50mg 24 hours following the 64mg study drug administration; It was a four week treatment and there was a seven-day washout period between dosing phases.
Study Design
Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Analgesia
Intervention
OROS® Hydromorphone HCL; OROS® Dilaudid; Dilaudid SR (slow release); Naltrexone (an opioid antagonist).
Status
Completed
Source
Alza Corporation, DE, USA
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00398957
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:41:38-0400
Clinical Trials
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...
The purpose of this repeated dose study is to develop recommended dosing information for initiation of therapy with OROS Hydromorphone HCI (slow release) in patients with chronic cancer pa...
The purpose of this study was to characterize the effectiveness and safety of OROS hydromorphone HCL and OxyContin in patients with chronic osteoarthritis (OA) of the knee or hip who are r...
The purpose of this study was to compare the analgesic (a drug that relieves pain) effectiveness and safety of OROS hydromorphone HCI (slow release) 8 mg and 16 mg to placebo (no drug) in ...
The purpose of this open-label, extension study is to characterize the safety, effectiveness, and impact on quality of life measures of long-term repeated dosing of OROS hydromorphone slow...
PubMed Articles
Formulating prescription opioids to limit abuse remains a priority. OROS® extended-release (ER) hydromorphone HCl (EXALGO®) may have low abuse potential. Three post-marketing studies of the relative...
A double blind, placebo-controlled randomized trial (NCT00253747) evaluating osmotic-release oral system methylphenidate (OROS-MPH) for smoking-cessation revealed a significant interaction effect in w...
Hydromorphone is a standard opioid analgesic for cancer pain that, prior to this study, was not approved in Japan, where options for opioid switching are limited. We aimed to investigate the efficacy ...
To date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid depende...
To determine if extended-release naltrexone (XR-NTX) would improve or maintain viral suppression (VS) among prisoners or jail detainees with HIV and opioid use disorders (OUD) transitioning to the com...
Medical and Biotech [MESH] Definitions
Naltrexone
Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.
Chemoembolization, Therapeutic
Administration of antineoplastic agents together with an embolizing vehicle. This allows slow release of the agent as well as obstruction of the blood supply to the neoplasm.
Methenamine
An anti-infective agent most commonly used in the treatment of urinary tract infections. Its anti-infective action derives from the slow release of formaldehyde by hydrolysis at acidic pH. (From Martindale, The Extra Pharmacopoeia, 30th ed, p173)
Hydromorphone
An opioid analgesic made from MORPHINE and used mainly as an analgesic. It has a shorter duration of action than morphine.
Slow Virus Diseases
Diseases of viral origin, characterized by incubation periods of months to years, insidious onset of clinical manifestations, and protracted clinical course. Though the disease process is protracted, viral multiplication may not be unusually slow. Conventional viruses produce slow virus diseases such as SUBACUTE SCLEROSING PANENCEPHALITIS, progressive multifocal leukoencephalopathy (LEUKOENCEPHALOPATHY, PROGRESSIVE MULTIFOCAL), and AIDS. Diseases produced by unconventional agents were originally considered part of this group. They are now called PRION DISEASES.
