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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00398957
Recruitment Status : Completed
First Posted : November 14, 2006
Last Update Posted : April 27, 2010
Information provided by:
Alza Corporation, DE, USA

Brief 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.

Condition or disease Intervention/treatment Phase
Analgesia Drug: OROS® Hydromorphone HCL; OROS® Dilaudid; Dilaudid SR (slow release); Naltrexone (an opioid antagonist). Phase 1

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  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Evaluation of the Dose Proportionality of Dilaudid SR (OROS� Hydromorphone HCL) Tablets 8mg, 16mg, 32mg, and 64mg
Actual Study Completion Date : September 1998

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. 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 :
  1. The secondary endpoints were the pharmacokinetic parameters for the study drug: Time to Peak Plasma Concentration and Terminal half-life.

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00398957

Sponsors and Collaborators
Alza Corporation, DE, USA
Study Director: Alza Corporation Clinical Trial ALZA

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00398957     History of Changes
Other Study ID Numbers: CR011611
First Posted: November 14, 2006    Key Record Dates
Last Update Posted: April 27, 2010
Last Verified: April 2010

Keywords provided by Alza Corporation, DE, USA:

Additional relevant MeSH terms:
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Analgesics, Opioid
Central Nervous System Depressants