Clinical trial NCT00399295: 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
Official title: An Open-Label Evaluation of the Independent Effect of Coadministration of a High Fat Meal and Naltrexone Blockade on the Pharmacokinetic Profile of Dilaudid OROS (Hydromorphone HCL) 16 mg
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Analgesia
Keywords: Analgesia
Lead sponsor: Alza Corporation, DE, USA
Sponsor class: INDUSTRY
First posted: 2006-11-14
Enrollment: 30
Sex: ALL
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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 outcomes:
measure: 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).
Other outcomes:
Locations:
Study officials:
affiliation: ALZA
name: Alza Corporation Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Sathyan G, Xu E, Thipphawong J, Gupta SK. Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence and absence of food. BMC Clin Pharmacol. 2007 Feb 2;7:2. doi: 10.1186/1472-6904-7-2.