Chronic Pain
Conditions
Keywords
Pharmacokinetics, Hydromorphone, Hydrocodone, APAP
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.
Interventions
DRUGHydrocodone
Dose: Standard prescribed dose Frequency: Once Duration: Once
Sponsors
Medtronic - MITG
International Clinical Research Institute
NEMA Research, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration of Hydromorphone | Up to 6 hours | Determine the plasma pharmacokinetic profile of hydromorphone in chronic pain subjects taking hydrocodone within a 6 hour time frame. Note: Sensitivity of the lab test used to determine plasma hydromorphone concentrations was not sufficient. Failure to meet the lowest level of detection, all subjects plasma hydromorphone concentrations were recorded as zero at all time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of Plasma PK of Hydrocodone | 1 Month | Correlate the plasma pharmacokinetic profile of hydromorphone to their hydrocodone doses. |
| Peak Urine Concentration of Hydromorphone | Up to 4 hours | Analyze the urine concentration of hydromorphone |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Hydrocodone: Dose: Standard prescribed dose Frequency: Once Duration: Once | 16 |
| 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.
Hydrocodone: Dose: Standard prescribed dose Frequency: Once Duration: Once | 14 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Group 1 | Total | Group 2 |
|---|---|---|---|
| Age, Continuous | 43.63 years STANDARD_DEVIATION 8.937 | 48.60 years STANDARD_DEVIATION 10.062 | 54.28 years STANDARD_DEVIATION 8.279 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 29 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 28 Participants | 13 Participants |
| Region of Enrollment United States | 16 participants | 30 participants | 14 participants |
| Sex: Female, Male Female | 11 Participants | 21 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 14 |
Outcome results
Primary
Peak Plasma Concentration of Hydromorphone
Determine the plasma pharmacokinetic profile of hydromorphone in chronic pain subjects taking hydrocodone within a 6 hour time frame. Note: Sensitivity of the lab test used to determine plasma hydromorphone concentrations was not sufficient. Failure to meet the lowest level of detection, all subjects plasma hydromorphone concentrations were recorded as zero at all time points.
Time frame: Up to 6 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 | Peak Plasma Concentration of Hydromorphone | Hour 2 | NA ng/mL | — |
| Group 1 | Peak Plasma Concentration of Hydromorphone | Hour 4 | NA ng/mL | — |
| Group 1 | Peak Plasma Concentration of Hydromorphone | Hour 1 | 0 ng/mL | Standard Deviation 0 |
| Group 1 | Peak Plasma Concentration of Hydromorphone | Hour 5 | 0 ng/mL | Standard Deviation 0 |
| Group 1 | Peak Plasma Concentration of Hydromorphone | Hour 3 | 0 ng/mL | Standard Deviation 0 |
| Group 1 | Peak Plasma Concentration of Hydromorphone | Hour 6 | NA ng/mL | — |
| Group 1 | Peak Plasma Concentration of Hydromorphone | Hour 0 | 0 ng/mL | Standard Deviation 0 |
| Group 2 | Peak Plasma Concentration of Hydromorphone | Hour 6 | 0 ng/mL | Standard Deviation 0 |
| Group 2 | Peak Plasma Concentration of Hydromorphone | Hour 0 | 0 ng/mL | Standard Deviation 0 |
| Group 2 | Peak Plasma Concentration of Hydromorphone | Hour 1 | NA ng/mL | — |
| Group 2 | Peak Plasma Concentration of Hydromorphone | Hour 2 | 0 ng/mL | Standard Deviation 0 |
| Group 2 | Peak Plasma Concentration of Hydromorphone | Hour 3 | NA ng/mL | — |
| Group 2 | Peak Plasma Concentration of Hydromorphone | Hour 4 | 0 ng/mL | Standard Deviation 0 |
| Group 2 | Peak Plasma Concentration of Hydromorphone | Hour 5 | NA ng/mL | — |
Secondary
Correlation of Plasma PK of Hydrocodone
Correlate the plasma pharmacokinetic profile of hydromorphone to their hydrocodone doses.
Time frame: 1 Month
Population: Analysis could not be performed because plasma levels analyzed were too low for the assay chosen.
Secondary
Peak Urine Concentration of Hydromorphone
Analyze the urine concentration of hydromorphone
Time frame: Up to 4 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 | Peak Urine Concentration of Hydromorphone | Hour 0 | 726.69 ng/mL | Standard Deviation 1294.77 |
| Group 1 | Peak Urine Concentration of Hydromorphone | Hour 3 | 815.63 ng/mL | Standard Deviation 1396.38 |
| Group 1 | Peak Urine Concentration of Hydromorphone | Hour 4 | NA ng/mL | — |
| Group 2 | Peak Urine Concentration of Hydromorphone | Hour 0 | 211.36 ng/mL | Standard Deviation 248.356 |
| Group 2 | Peak Urine Concentration of Hydromorphone | Hour 3 | NA ng/mL | — |
| Group 2 | Peak Urine Concentration of Hydromorphone | Hour 4 | 205.57 ng/mL | Standard Deviation 239.508 |