Clinical trial NCT01517295: Pharmacokinetic Study of Hydrocodone/APAP in Chronic Pain Patients
Official title: Evaluating the Pharmacokinetic Profile of Hydromorphone in Chronic Pain Patients Taking Hydrocodone/APAP
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Pain
Keywords: Pharmacokinetics
Hydromorphone
Hydrocodone
APAP
Lead sponsor: NEMA Research, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Medtronic - MITG
name: International Clinical Research Institute
First posted: 2012-01-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: 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.

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 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.

Primary outcomes:
measure: Peak Plasma Concentration of Hydromorphone
timeFrame: Up to 6 hours
Secondary outcomes:
measure: Correlation of Plasma PK of Hydrocodone
timeFrame: 1 Month
measure: Peak Urine Concentration of Hydromorphone
timeFrame: Up to 4 hours
Other outcomes:
Locations:
city: Naples
country: United States
facility: NEMA Research Inc. (CRO)
state: Florida
city: Leawood
country: United States
facility: International Clinical Research Institute
state: Kansas
Study officials:
affiliation: International Clinical Research Institute
name: Srinivas Nalamachu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NEMA Research, Inc.
name: Joseph Pergolizzi, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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. doi: 10.1016/s1570-0232(01)00616-x.
citation: 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. doi: 10.1016/s1570-0232(02)00856-5.
citation: 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. doi: 10.1046/j.1365-2125.2003.02002.x.
citation: 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. doi: 10.1111/j.2042-7158.1979.tb13507.x.
citation: 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. doi: 10.1038/clpt.1993.177.