An Open-Label Evaluation of the Dose Proportionality of OROS� Hydromorphone HCL Tablets 8mg, 16mg, 32mg, 64mg

An Open Label Evaluation of the Dose Proportionality of Dilaudid SR (OROS� Hydromorphone HCL) Tablets 8mg, 16mg, 32mg, and 64mg

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.

Study Overview

• Status: Completed
• Conditions: Analgesia
• Intervention / Treatment: Drug: OROS® Hydromorphone HCL; OROS® Dilaudid; Dilaudid SR (slow release); Naltrexone (an opioid antagonist).

Detailed 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 Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients were non-smoking, healthy volunteers with body weight between 135 and 220 pounds and within +/- 10% of their recommended weight range for their height and body frame according to the Metropolitan Height and Weight Tables
• Patients had a negative baseline urine screen for drugs of abuse
• Patients did not have any clinically significant deviations from normal in any laboratory test value.

Exclusion Criteria:

• Patients intolerant of or hypersensitive to hydromorphone or naltrexone
• Patient with any gastrointestinal disorder that may affect the absorption of orally administered drugs
• Patients with depressed respiratory function
• Patient with impaired renal or hepatic function
• Patient with dependence to opiates
• pregnant or breast feeding
• Female patients of child bearing potential must have a negative pregnancy test each week prior to administration of study drug and required to be following a medically rhydromorphoneadministrationnaltrexone recognized contraceptive program prior to and during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The primary endpoints for the statistical evaluations of the study drug were: Area Under the Concentration-Time Curve from 0 to Infinity, Area Under the Concentration-Time Curve from 0 to time t and Peak Plasma Concentration.

Secondary Outcome Measures

Outcome Measure
The secondary endpoints were the pharmacokinetic parameters for the study drug: Time to Peak Plasma Concentration and Terminal half-life.

Collaborators and Investigators

• Sponsor: Alza Corporation, DE, USA

Publications and helpful links

General Publications

• Sathyan G, Xu E, Thipphawong J, Gupta SK. Pharmacokinetic investigation of dose proportionality with a 24-hour controlled-release formulation of hydromorphone. BMC Clin Pharmacol. 2007 Feb 2;7:3. doi: 10.1186/1472-6904-7-3.

Study record dates

Study Major Dates

• Study Completion (Actual): September 1, 1998

Study Registration Dates

• First Submitted: November 10, 2006
• First Submitted That Met QC Criteria: November 10, 2006
• First Posted (Estimate): November 14, 2006

Study Record Updates

• Last Update Posted (Estimate): April 27, 2010
• Last Update Submitted That Met QC Criteria: April 26, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: Analgesia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Alcohol Deterrents; Naltrexone; Hydromorphone; Narcotic Antagonists
• Other Study ID Numbers: CR011611