Pharmacokinetic Study of Hydrocodone/APAP in Chronic Pain Patients - Full Text View

Purpose

Objective is to evaluate the pharmacokinetics profile of hydrocodone's metabolite hydromorphone in patients who are taking hydrocodone on a routine basis for more than 3 months for chronic pain and correlate hydromorphone levels to their hydrocodone usage.

Condition	Intervention	Phase
Chronic Pain	Drug: Hydrocodone	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Open Label
Official Title:	Evaluating the Pharmacokinetic Profile of Hydromorphone in Chronic Pain Patients Taking Hydrocodone/APAP

Resource links provided by NLM:

MedlinePlus related topics: Chronic Pain Urine and Urination

Drug Information available for: Hydromorphone hydrochloride Hydrocodone Hydrocodone bitartrate Hydromorphone Hycodan

U.S. FDA Resources

Further study details as provided by NEMA Research, Inc.:

Primary Outcome Measures:

Peak Plasma concentration of hydromorphone [ Time Frame: Up to 6 hours ] [ Designated as safety issue: No ]
Determine the plasma pharmacokinetic profile of hydromorphone in chronic pain subjects taking hydrocodone within a 6 hour time frame.

Secondary Outcome Measures:

Correlation of plasma PK of hydrocodone [ Time Frame: 1 Month ] [ Designated as safety issue: No ]
Correlate the plasma pharmacokinetic profile of hydromorphone to their hydrocodone doses.
Peak Urine concentration of hydromorphone [ Time Frame: Up to 4 hours ] [ Designated as safety issue: No ]
Analyze the urine concentration of hydromorphone

Enrollment:	30
Study Start Date:	February 2012
Study Completion Date:	September 2012
Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 1 Blood will be drawn at 0, 1, 3, and 5 hours after taking one dose of hydrocodone/APAP. Urine will be taken at hour 0 and 3.	Drug: Hydrocodone Dose: Standard prescribed dose Frequency: Once Duration: Once Other Names: Hydrocodone/APAP Vicodin
Experimental: Group 2 Blood will be drawn at 0, 2, 4, and 6 hours after one dose of hydrocodone/APAP. Urine will be taken at hour 0 and 4.	Drug: Hydrocodone Dose: Standard prescribed dose Frequency: Once Duration: Once Other Names: Hydrocodone/APAP Vicodin

Detailed Description:

Hydrocodone combinations are the most commonly prescribed pain medications in the United States. All the current available Hydrocodone formulations are short acting and have Acetaminophen/Ibuprofen in them. Chronic pain patients who take pain medications for extended time are overloaded with Acetaminophen and there is a very serious concern about liver failure from excessive concurrent alcohol use. Also all the current hydrocodone combinations available in the U.S. are short acting and provide pain relief for 3-6 hrs.

Hydromorphone is a metabolite of Hydrocodone and plays a significant role in providing pain relief in these patients. Although there are no long acting or extended release hydrocodone formulations that are FDA approve at this time, there is once a day extended release Hydromorphone (ER) approved by FDA and is currently marketed under the name Exalgo ®. PK study of chronic hydrocodone/acetaminophen usage is important to determine equivalent potency with hydromorphone ER, so that clinicians can use a simple conversion formula to switch to hydromorphone ER.

Although medical professionals use the Opiate conversion formula on a regular basis for Opioid rotation, there are no published studies showing the pharmacokinetic data in patients taking hydrocodone for chronic pain.

Our goal is to use this PK data to guide clinicians with this data in using extended release hydromorphone for chronic pain management to provide predictable pain relief and minimize the acetaminophen usage.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Man or woman aged 18-75
Documented clinical diagnosis of chronic pain.
Have been taking hydrocodone/APAP for their chronic non-cancer pain.
Subjects currently on hydrocodone/APAP must be taking minimal daily dose of 15mg of Hydrocodone for at least 30 days.
Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

Subjects who are taking concomitant medications or Nutraceuticals that interfere with Hydrocodone metabolism as listed in Appendix 11 and/or as deemed clinically significant by a pharmacovigilance team that is contracted to monitor and advise.
Health concerns that the study physician feels may confound study results.
Individuals who are cognitively impaired or who are not able to give informed consent.
Previous participation in a clinical research trial within 30 days prior to randomization.
The subject has an ongoing abuse of illicit substances, alcohol, or actively smoking marijuana.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01517295

Locations

United States, Florida
NEMA Research Inc. (CRO)
Naples, Florida, United States, 34108
United States, Kansas
International Clinical Research Institute
Leawood, Kansas, United States, 66211

Sponsors and Collaborators

NEMA Research, Inc.

Covidien

International Clinical Research Institute

Investigators

Principal Investigator:	Srinivas Nalamachu, MD	International Clinical Research Institute
Study Director:	Joseph Pergolizzi, MD	NEMA Research, Inc.

More Information

Publications:

Wu Y. [Studies on the analysis of hydrocodone and its metabolite in human urine by GC/MS]. Yao Xue Xue Bao. 1997 Apr;32(4):305-9. Chinese.

Chen YL, Hanson GD, Jiang X, Naidong W. Simultaneous determination of hydrocodone and hydromorphone in human plasma by liquid chromatography with tandem mass spectrometric detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Mar 25;769(1):55-64.

Menelaou A, Hutchinson MR, Quinn I, Christensen A, Somogyi AA. Quantification of the O- and N-demethylated metabolites of hydrocodone and oxycodone in human liver microsomes using liquid chromatography with ultraviolet absorbance detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Feb 25;785(1):81-8.

Hutchinson MR, Menelaou A, Foster DJ, Coller JK, Somogyi AA. CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes. Br J Clin Pharmacol. 2004 Mar;57(3):287-97.

Cone EJ, Darwin WD, Gorodetzky CW. Comparative metabolism of codeine in man, rat, dog, guinea-pig and rabbit: identification of four new metabolites. J Pharm Pharmacol. 1979 May;31(5):314-7.

Otton SV, Schadel M, Cheung SW, Kaplan HL, Busto UE, Sellers EM. CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone. Clin Pharmacol Ther. 1993 Nov;54(5):463-72.

Responsible Party:	NEMA Research, Inc.
ClinicalTrials.gov Identifier:	NCT01517295 History of Changes
Other Study ID Numbers:	NEMA-HydrocodonePK-001
Study First Received:	January 4, 2012
Last Updated:	September 30, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by NEMA Research, Inc.:

Pharmacokinetics
Hydromorphone
Hydrocodone
APAP

Additional relevant MeSH terms:

Acetaminophen
Hydromorphone
Hydrocodone
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Analgesics, Opioid
Central Nervous System Depressants
Narcotics
Antitussive Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on May 16, 2013