Chronic PainPhase 4NCT01517295
Pharmacokinetic Study of Hydrocodone/APAP in Chronic Pain Patients
A Phase 4 study testing Hydrocodone in people with Chronic Pain, run by NEMA Research, Inc. at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Pain
- What is being tested?
- Hydrocodone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2012to Sep 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
International Clinical Research Institute
Leawood, Kansas, 66211
NEMA Research Inc. (CRO)
Naples, Florida, 34108
About this study
Official title: Evaluating the Pharmacokinetic Profile of Hydromorphone in Chronic Pain Patients Taking Hydrocodone/APAP
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.
Read the 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.
- Conditions
- Chronic Pain
- Being tested
- Hydrocodone
- Keywords
- Pharmacokinetics, Hydromorphone, Hydrocodone, APAP
- Medical subject headings
- Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydrocodoneDrug
Also called Hydrocodone/APAP, Vicodin
Dose: Standard prescribed dose Frequency: Once Duration: Once
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | 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. Receives: Drug: Hydrocodone |
| Group 2 | Experimental | 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. Receives: Drug: Hydrocodone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 6 hours
Secondary outcomes (2)
Correlation of Plasma PK of Hydrocodone
Correlate the plasma pharmacokinetic profile of hydromorphone to their hydrocodone doses.
Measured: 1 Month
Peak Urine Concentration of Hydromorphone
Analyze the urine concentration of hydromorphone
Measured: Up to 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study startFeb 2012
- Primary completionMay 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- NEMA Research, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medtronic - MITG, International Clinical Research Institute
- Responsible party
- Sponsor
- Investigators
- Srinivas Nalamachu, MD, Principal investigator, International Clinical Research InstituteJoseph Pergolizzi, MD, Study director, NEMA Research, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01517295
- Sponsor's protocol ID
- NEMA-HydrocodonePK-001
- Status last verified
- Jun 2016
- First submitted
- 4 Jan 2012
- Last updated
- 28 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 11499035Chen 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.
PubMed 11936695Menelaou 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.
PubMed 12535841Hutchinson 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.
PubMed 14998425Cone 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.
PubMed 37301Otton 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.
PubMed 7693389
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Pharmacokinetic Profile of Hydromorphone in Chronic Pain Patients Taking Hydrocodone/APAP
- ClinicalTrials.gov ID
- NCT01517295
- Acronym / sponsor ID
- NEMA-HydrocodonePK-001
- Conditions
- Chronic Pain
- Keywords
- Pharmacokinetics, Hydromorphone, Hydrocodone, APAP
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- NEMA Research, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Medtronic - MITG, International Clinical Research Institute
- Study start
- Feb 2012
- Primary completion
- May 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 25 Jan 2012 (estimated)
- Results
- Posted 28 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: HydrocodoneBlood 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. |
| Group 2 | Experimental | Drug: HydrocodoneBlood 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydrocodoneAlso: Hydrocodone/APAP, VicodinDose: Standard prescribed dose Frequency: Once Duration: Once | Drug | Group 1, Group 2 |
Primary outcome
Peak Plasma Concentration of Hydromorphone
Time frame: 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.
2 secondary outcomes
Correlation of Plasma PK of Hydrocodone
Time frame: 1 Month
Peak Urine Concentration of Hydromorphone
Time frame: Up to 4 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11499035Wu 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.
- Background: PubMed 11936695Chen 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.
- Background: PubMed 12535841Menelaou 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.
- Background: PubMed 14998425Hutchinson 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.
- Background: PubMed 37301Cone 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.
- Background: PubMed 7693389Otton 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Srinivas Nalamachu, MD principal investigator
International Clinical Research Institute
Joseph Pergolizzi, MD study director
NEMA Research, Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydrocodone in people with Chronic Pain, run by NEMA Research, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak Plasma Concentration of Hydromorphone (time frame: Up to 6 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01517295, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2016.