Renal ImpairmentPhase 1NCT01319266
A Study to Assess the Pharmacokinetics of the Hydrocodone Extended-Release Tablet (CEP-33237) in Subjects With Normal Renal Function and Subjects With Varying Degrees of Renal Impairment
A Phase 1 study testing Hydrocodone Bitartrate extended-release tablet in people with Renal Impairment, run by Cephalon at 4 sites in United States.
Trial summary
The purpose of this study is to assess the effect of varying degrees of renal impairment (mild, moderate, severe and end stage renal disease) compared with subjects with normal renal function on the pharmacokinetics of the hydrocodone bitartrate extended-release tablet. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Renal Impairment
- What is being tested?
- Hydrocodone Bitartrate extended-release tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 4 sitesUnited States
- Study dates
- Mar 2011to Oct 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All subjects:
- Written informed consent is obtained.
- The subject is a man or woman at least 18 years of age, with a body mass index (BMI) of 20 kg/m2 or more.
- Women must be surgically sterile, 2 years postmenopausal, or, if of child-bearing potential, be using a medically accepted method of contraception, and agree to continued use of this method for the duration of the study and for 30 days after discontinuation of study drug.
- The subject is a nonsmoker or smokes less than 10 cigarettes per day.
- The subject's vitamin usage is stable for at least 2 weeks before study drug administration and the subject's prescription and over-the-counter (OTC) medication dosage is stable.
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- The subject must be willing and able to comply with study restrictions and to remain at the clinic for the required duration of the administration period during the study.
- Subjects with normal renal function:
- The subject is in generally good health as determined by medical and psychiatric history, physical examination, ECG, serum chemistry, hematology, urinalysis, and serology.
- The subject has an estimated creatinine clearance >80 mL/min.
- Subjects with renal impairment:
- Subjects may have concurrent stable medical conditions in addition to renal impairment but may be included only if the investigator and protocol-specified contact for medical issues consider that the condition will not introduce an additional risk factor, and will not interfere with the study objectives and procedures (e.g., subjects with diabetes that has been stable, essential hypertension).
- Subjects are renally impaired as defined by 1 of the following categories:
- subjects with ESRD must be on hemodialysis for at least 6 months prior to enrollment and be receiving standard in-center thrice weekly treatments
- subjects with severe renal impairment must have an estimated creatinine clearance of less than 30 mL/min
- subjects with moderate renal impairment must have an estimated creatinine clearance of 30-50 mL/min
- subjects with mild renal impairment must have an estimated creatinine clearance of greater than 50 and up to 80 mL/min
Who cannot join
- All subjects:
- The subject is a poor metabolizer of cytochrome P450 (CYP) 2D6 substrates based on genotyping performed at screening.
- The subject has used an inducer (other than weak inducers) of CYP3A4/5 or CYP2D6 within 28 days prior to study drug administration. NOTES: Topical use of a medication that is known to be an inducer of CYP3A4/5 or CYP2D6 may be permitted after consultation with the medical monitor. No medication will be permitted within 2 hours before or after study drug administration.
- The subject has used an inhibitor (other than weak inhibitors) of CYP3A4/5 or CYP2D6 within 14 days or 5 half-lives (whichever is longer) prior to study drug administration. NOTES: Topical use of a medication that is known to be an inhibitor of CYP3A4/5 or CYP2D6 may be permitted after consultation with the medical monitor. No medication will be permitted within 2 hours before or after study drug administration.
- The subject is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
- The subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery, excluding appendectomy). Note: Cholecystectomy performed 2 years or more prior to enrollment is permitted.
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- The subject has previously participated in a study with CEP-33237.
- The subject has a known sensitivity or idiosyncratic reaction to any compound present in hydrocodone or hydromorphone, its related compounds, or to any metabolites, or naltrexone, or any compound listed as being present in a study formulation.
- The subject is unlikely to comply with the study protocol, or is unsuitable for any other reasons, as judged by the investigator.
- Subjects with normal renal function:
- The subject has any clinically significant, uncontrolled medical condition (treated or untreated).
- The subject has a clinically significant deviation from normal in ECG or physical examination findings, as determined by the investigator or the protocol-specified contact for medical issues.
- Subjects with normal renal function who have a hemoglobin value of less than 12 g/dL.
- Subjects with renal impairment:
- The subject has a condition that, in the opinion of the investigator or protocol-specified contact for medical issues, will introduce an additional risk factor or interfere with the study objectives and procedures.
- The subject has evidence of an unstable clinically important medical condition other than impaired renal function.
- The subject has an acute exacerbation or unstable renal function, as indicated by worsening of clinical and/or laboratory signs of renal impairment, within the 4 weeks before study drug administration.
- The subject has an acute renal disease caused by infection or drug toxicity.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
New Orleans Center
Knoxville, Tennessee, 37920
Clinical Pharmacology of Miami
Miami, Florida, 33014
DaVita
Minneapolis, Minnesota, 55404
Orlando Clinical Research
Orlando, Florida, 32809
About this study
Official title: An Open-Label, Single-Dose Study to Assess the Pharmacokinetics of the Hydrocodone Bitartrate Extended-Release Tablet (45 mg) in Subjects With Normal Renal Function and Subjects With Varying Degrees of Renal Impairment
The purpose of this study is to assess the effect of varying degrees of renal impairment (mild, moderate, severe and end stage renal disease) compared with subjects with normal renal function on the pharmacokinetics of the hydrocodone bitartrate extended-release tablet.
Read the detailed description
This is a multicenter, open-label, parallel-group pharmacokinetic and safety study to assess the effect of varying degrees of renal impairment (mild, moderate, severe and end stage renal disease [ESRD])on the pharmacokinetics of the hydrocodone bitartrate extended-release tablet at a single dose of 45 mg as compared with subjects with normal renal function. The study consists of a screening visit within 28 days before study drug administration (visit 1), followed by a single-dose administration period including a 144-hour pharmacokinetic sampling period (visit 2) with a final assessment after the final pharmacokinetic sample is collected or upon early withdrawal, and a follow-up visit 48 to 72 hours after the last discharge from the study center (visit 3). Subjects will be categorized into either the control group with normal renal function or one of the four groups of subjects with varying degrees of renal impairment. Up to 12 subjects in each of the 4 renal impairment groups and up to 16 subjects with normal renal function will be enrolled to achieve the targeted minimum of 8 subjects in each renal impairment group and 10 subjects with normal renal function completing the study. Eligible subjects will check in to the study center on day -1. Subjects who continue to meet the criteria for enrollment will receive a single dose of the hydrocodone bitartrate extended-release tablet on day 1. Subjects will receive one 50-mg tablet of naltrexone hydrochloride to block opioid receptors and minimize opioid related adverse events approximately 15 and 3 hours before and approximately 9 and 21 hours after study drug administration. Blood and urine samples will be collected just before study drug administration and over a 144-hour period after study drug administration. Safety will be assessed throughout the study by monitoring the occurrence of adverse events, clinical laboratory test results, vital signs measurements,12-lead ECG findings, physical examination findings, SpO2 findings, and use of concomitant medications. Subjects who complete all scheduled visits will have final procedures and assessments performed prior to discharge from the study center after pharmacokinetic sampling is complete. All subjects will be asked to return for a follow-up visit.
- Conditions
- Renal Impairment
- Being tested
- Hydrocodone Bitartrate extended-release tablet
- Keywords
- hydrocodone, extended release, pharmacokinetics, renal impairment
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydrocodone Bitartrate extended-release tabletDrug
Also called CEP-33237
Hydrocodone bitartrate extended-release oral tablet will be administered at a dose of 45 mg and dosed one time on Day 1. Subjects will also be dosed with naltrexone hydrochloride to block opioid effects.
| Study group | Role | What they receive |
|---|---|---|
| Normal Renal Function | Experimental | Subjects with normal renal function Receives: Drug: Hydrocodone Bitartrate extended-release tablet |
| Mild Renal Impairment | Experimental | Subjects with mild renal impairment (defined by an estimated creatinine clearance of > 50 and up to 80 mL/min) Receives: Drug: Hydrocodone Bitartrate extended-release tablet |
| Moderate Renal Impairment | Experimental | Subjects with moderate renal impairment (defined by an estimated creatinine clearance of 30-50 mL/min) Receives: Drug: Hydrocodone Bitartrate extended-release tablet |
| Severe Renal Impairment | Experimental | Subjects with severe renal impairment (defined by an estimated creatinine clearance of less than 30 mL/min) Receives: Drug: Hydrocodone Bitartrate extended-release tablet |
| End Stage Renal Disease (ESRD) | Experimental | Subjects with ESRD (defined as being on hemodialysis for at least 6 months prior to enrollment and be receiving standard in-center dialysis treatments three times a week) Receives: Drug: Hydrocodone Bitartrate extended-release tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma drug concentration (Cmax)
Measured: Between baseline and 144 hours following drug administration
Area under the plasma drug concentration-by-time curve (AUC) from time 0 to infinity (AUC0-∞)
Measured: Between baseline and 144 hours following drug administration
Secondary outcomes (1)
Assess the safety of a single 45-mg dose of the hydrocodone bitartrate extended release tablet
by evaluating the following:
- occurrence of adverse events throughout the study
- clinical laboratory (serum chemistry, hematology, and urinalysis) test results at final assessment or early withdrawal
- vital signs measurements (blood pressure, pulse, and respiratory rate) throughout the study
- 12-lead electrocardiogram (ECG) findings at final assessment or early withdrawal
- physical examination findings at final assessment or early withdrawal
- oxyhemoglobin saturation (SpO2) monitoring throughout the study
- concomitant medication usage throughout the study
Measured: Safety will be assessed from the start of study drug administration through the follow-up visit 48 to 72 hours after discharge from the study center.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2011 (estimated)
- Study startMar 2011
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal ImpairmentStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cephalon
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sponsor's Medical Expert, Study director, Cephalon, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01319266
- Sponsor's protocol ID
- C33237/1088
- Status last verified
- Apr 2012
- First submitted
- 17 Mar 2011
- Last updated
- 24 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Single-Dose Study to Assess the Pharmacokinetics of the Hydrocodone Bitartrate Extended-Release Tablet (45 mg) in Subjects With Normal Renal Function and Subjects With Varying Degrees of Renal Impairment
- ClinicalTrials.gov ID
- NCT01319266
- Acronym / sponsor ID
- C33237/1088
- Conditions
- Renal Impairment
- Keywords
- hydrocodone, extended release, pharmacokinetics, renal impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- CephalonIndustry (pharma, biotech, devices)
- Study start
- Mar 2011
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 21 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the effect of varying degrees of renal impairment (mild, moderate, severe and end stage renal disease) compared with subjects with normal renal function on the pharmacokinetics of the hydrocodone bitartrate extended-release tablet.
Detailed description
This is a multicenter, open-label, parallel-group pharmacokinetic and safety study to assess the effect of varying degrees of renal impairment (mild, moderate, severe and end stage renal disease [ESRD])on the pharmacokinetics of the hydrocodone bitartrate extended-release tablet at a single dose of 45 mg as compared with subjects with normal renal function. The study consists of a screening visit within 28 days before study drug administration (visit 1), followed by a single-dose administration period including a 144-hour pharmacokinetic sampling period (visit 2) with a final assessment after the final pharmacokinetic sample is collected or upon early withdrawal, and a follow-up visit 48 to 72 hours after the last discharge from the study center (visit 3). Subjects will be categorized into either the control group with normal renal function or one of the four groups of subjects with varying degrees of renal impairment. Up to 12 subjects in each of the 4 renal impairment groups and up to 16 subjects with normal renal function will be enrolled to achieve the targeted minimum of 8 subjects in each renal impairment group and 10 subjects with normal renal function completing the study. Eligible subjects will check in to the study center on day -1. Subjects who continue to meet the criteria for enrollment will receive a single dose of the hydrocodone bitartrate extended-release tablet on day 1. Subjects will receive one 50-mg tablet of naltrexone hydrochloride to block opioid receptors and minimize opioid related adverse events approximately 15 and 3 hours before and approximately 9 and 21 hours after study drug administration. Blood and urine samples will be collected just before study drug administration and over a 144-hour period after study drug administration. Safety will be assessed throughout the study by monitoring the occurrence of adverse events, clinical laboratory test results, vital signs measurements,12-lead ECG findings, physical examination findings, SpO2 findings, and use of concomitant medications. Subjects who complete all scheduled visits will have final procedures and assessments performed prior to discharge from the study center after pharmacokinetic sampling is complete. All subjects will be asked to return for a follow-up visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Normal Renal Function | Experimental | Drug: Hydrocodone Bitartrate extended-release tabletSubjects with normal renal function |
| Mild Renal Impairment | Experimental | Drug: Hydrocodone Bitartrate extended-release tabletSubjects with mild renal impairment (defined by an estimated creatinine clearance of > 50 and up to 80 mL/min) |
| Moderate Renal Impairment | Experimental | Drug: Hydrocodone Bitartrate extended-release tabletSubjects with moderate renal impairment (defined by an estimated creatinine clearance of 30-50 mL/min) |
| Severe Renal Impairment | Experimental | Drug: Hydrocodone Bitartrate extended-release tabletSubjects with severe renal impairment (defined by an estimated creatinine clearance of less than 30 mL/min) |
| End Stage Renal Disease (ESRD) | Experimental | Drug: Hydrocodone Bitartrate extended-release tabletSubjects with ESRD (defined as being on hemodialysis for at least 6 months prior to enrollment and be receiving standard in-center dialysis treatments three times a week) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Written informed consent is obtained.
- The subject is a man or woman at least 18 years of age, with a body mass index (BMI) of 20 kg/m2 or more.
- Women must be surgically sterile, 2 years postmenopausal, or, if of child-bearing potential, be using a medically accepted method of contraception, and agree to continued use of this method for the duration of the study and for 30 days after discontinuation of study drug.
- The subject is a nonsmoker or smokes less than 10 cigarettes per day.
- The subject's vitamin usage is stable for at least 2 weeks before study drug administration and the subject's prescription and over-the-counter (OTC) medication dosage is stable.
Key exclusion criteria (18 listed)
- The subject is a poor metabolizer of cytochrome P450 (CYP) 2D6 substrates based on genotyping performed at screening.
- The subject has used an inducer (other than weak inducers) of CYP3A4/5 or CYP2D6 within 28 days prior to study drug administration. NOTES: Topical use of a medication that is known to be an inducer of CYP3A4/5 or CYP2D6 may be permitted after consultation with the medical monitor. No medication will be permitted within 2 hours before or after study drug administration.
- The subject has used an inhibitor (other than weak inhibitors) of CYP3A4/5 or CYP2D6 within 14 days or 5 half-lives (whichever is longer) prior to study drug administration. NOTES: Topical use of a medication that is known to be an inhibitor of CYP3A4/5 or CYP2D6 may be permitted after consultation with the medical monitor. No medication will be permitted within 2 hours before or after study drug administration.
- The subject is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
- The subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery, excluding appendectomy). Note: Cholecystectomy performed 2 years or more prior to enrollment is permitted.
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 |
|---|---|---|
| Hydrocodone Bitartrate extended-release tabletAlso: CEP-33237Hydrocodone bitartrate extended-release oral tablet will be administered at a dose of 45 mg and dosed one time on Day 1. Subjects will also be dosed with naltrexone hydrochloride to block opioid effects. | Drug | End Stage Renal Disease (ESRD), Mild Renal Impairment, Moderate Renal Impairment, Normal Renal Function, Severe Renal Impairment |
Primary outcome
Maximum observed plasma drug concentration (Cmax)
Time frame: Between baseline and 144 hours following drug administration
Area under the plasma drug concentration-by-time curve (AUC) from time 0 to infinity (AUC0-∞)
Time frame: Between baseline and 144 hours following drug administration
1 secondary outcome
Assess the safety of a single 45-mg dose of the hydrocodone bitartrate extended release tablet
Time frame: Safety will be assessed from the start of study drug administration through the follow-up visit 48 to 72 hours after discharge from the study center.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2012.
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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.
Sponsor's Medical Expert study director
Cephalon, Inc.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hydrocodone Bitartrate extended-release tablet in people with Renal Impairment, run by Cephalon at 4 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 17 inclusion and 18 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 24 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum observed plasma drug concentration (Cmax) (time frame: Between baseline and 144 hours following drug administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Apr 2012.