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

NCT01319266 | Completed Phase 1

• 1 other identifier: C33237/1088
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Renal Impairment

Keywords

hydrocodone; extended release; pharmacokinetics; renal impairment

Outcome Measures

Primary Outcomes (2)

• Maximum observed plasma drug concentration (Cmax)

  Between baseline and 144 hours following drug administration

• Area under the plasma drug concentration-by-time curve (AUC) from time 0 to infinity (AUC0-∞)

  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

  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.

Study Arms (5)

Normal Renal Function

EXPERIMENTAL

Subjects with normal renal function

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)

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)

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)

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)

Drug: Hydrocodone Bitartrate extended-release tablet

Interventions

Hydrocodone Bitartrate extended-release tablet DRUG

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.

Also known as: CEP-33237

End Stage Renal Disease (ESRD); Mild Renal Impairment; Moderate Renal Impairment; Normal Renal Function; Severe Renal Impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cephalon: lead

Study Sites (4)

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

Location

Orlando Clinical Research

Orlando, Florida, 32809, United States

Location

DaVita

Minneapolis, Minnesota, 55404, United States

Location

New Orleans Center

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Sponsor's Medical Expert

  Cephalon, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2011
• First Posted: March 21, 2011
• Study Start: March 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: April 24, 2012

Record last verified: 2012-04

Locations

US (4)