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

April 20, 2012 updated by: Cephalon

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
55

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33014
        • Clinical Pharmacology of Miami
      • Orlando, Florida, United States, 32809
        • Orlando Clinical Research
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Davita
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • New Orleans Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

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.
  • 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

Key Exclusion Criteria:

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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Normal Renal Function
Subjects with normal renal function
Drug: Hydrocodone Bitartrate extended-release tablet
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.
Other Names:
  • CEP-33237
Experimental: Mild Renal Impairment
Subjects with mild renal impairment (defined by an estimated creatinine clearance of > 50 and up to 80 mL/min)
Drug: Hydrocodone Bitartrate extended-release tablet
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.
Other Names:
  • CEP-33237
Experimental: Moderate Renal Impairment
Subjects with moderate renal impairment (defined by an estimated creatinine clearance of 30-50 mL/min)
Drug: Hydrocodone Bitartrate extended-release tablet
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.
Other Names:
  • CEP-33237
Experimental: Severe Renal Impairment
Subjects with severe renal impairment (defined by an estimated creatinine clearance of less than 30 mL/min)
Drug: Hydrocodone Bitartrate extended-release tablet
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.
Other Names:
  • CEP-33237
Experimental: End Stage Renal Disease (ESRD)
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)
Drug: Hydrocodone Bitartrate extended-release tablet
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.
Other Names:
  • CEP-33237

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Maximum observed plasma drug concentration (Cmax)
Time Frame: Between baseline and 144 hours following drug administration
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
Between baseline and 144 hours following drug administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.

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
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cephalon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 21, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 24, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 20, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • C33237/1088

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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