Pharmacokinetic Study of Hydrocodone/APAP in Chronic Pain Patients

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.

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.