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

Alza Corporation

Status and phase

Completed

Phase 1

Conditions

Analgesia

Treatments

Drug: Hydromorphone HCL 16mg; Dilaudid SR 16mg; Naltrexone (opioid antagonist) 50mg.

Study type

Interventional

Funder types

Industry

Identifiers

NCT00399295

CR011608

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 patients

Sex

All

Ages

19 to 50 years old

Volunteers

Accepts Healthy Volunteers

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.