An Open-Label Evaluation of the Independent Effects of Coadministration of a High-Fat Meal and Naltrexone Blockade on the Pharmacokinetic Profile of Dilaudid OROS (Hydromorphone HCI) 16mg

Phase 1

Completed

• Conditions: Analgesia

• Registration Number: NCT00399295
• Lead Sponsor: Alza Corporation, DE, USA

Brief Summary

The purpose of this study was to compare the pharmacokinetic (the way a drug enters and leaves the blood and tissues over time) profile of Dilaudid OROS 16mg (Dilaudid Slow Release; hydromorphone HCL) administered under fasting conditions, following a high-fat breakfast meal. The study also examined the effect of naltrexone blockade on the pharmacokinetic profile of Dilaudid SR.

Detailed Description

This was a randomized (patients are assigned different treatments based on chance), open-label, three-way crossover study, performed in normal, healthy adults. Each patient received orally administered treatments (a different treatment during each dosing phase): Treatment A: single dose of Dilaudid SR 16 mg administered under fasting conditions without the naltrexone block;Treatment B: single dose of Dilaudid SR 16 mg administered under fed conditions without the naltrexone block, Treatment C: single dose of Dilaudid SR 16 mg administered under fasting conditions with naltrexone HCL 50mg block (3 oral doses of 50mg each administered 12 hours prior to , at the time of, and 12 hours after Dilaudid SR 16mg administration). There was a 7-day washout period between 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 Dilaudid SR administration. LC/MS/MS (Liquid Chromatography/Mass Spectroscopy/Mass Spectroscopy)techniques were employed for the analysis of plasma for hydromorphone concentration. Each patient randomly received orally-administered treatments of single dose of Dilaudid SR 16mg; under fasting conditions without the naltrexone block; under fed conditions without naltrexone block; under fasting conditions with naltrexone 50mg block (3 oral doses of 50mg naltrexone HCL each administered 12 hours prior to, at the time of, and 12 hours after hydromorphone administration); 7-day washout period between dosing phases.

Study Timeline

• Study Completion: 1997-06
• Study First Submitted: 2006-11-10
• Study First Submitted QC: 2006-11-10
• Study First Posted: 2006-11-14
• Status Verified: 2010-04
• Last Update Submitted: 2010-04-26
• Last Update Posted: 2010-04-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Patients were non-smoking, healthy volunteers with body weights between 135 and 220 pounds and within + - 10% of their recommended weight range for their height and body frame according to the 1984 Metropolitan Height and Weight Tables
• A negative baseline urine drug screen for cannabinoids, opiates, cocaine, ethanol and barbiturates.

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
The primary endpoints for the statistical evaluations of the study drug were: Area Under the Concentration-Time Curve from 0 to Infinity and Peak Plasma Concentration.

Secondary Outcome Measures

Name	Time	Method
Secondary endpoints were the parameters for the study drug: Area Under the Concentration-Time Curve from 0 to Time t, Time to Peak Plasma Concentration and Terminal Half Life).