Buprenorphine Accumulation and Description of Its Metabolites During Co-Medication of Buprenorphine Transdermal System (BTDS) and Ketoconazole

Condition(s) targeted: Healthy

Intervention: Buprenorphine transdermal patch (Drug); Ketoconazole tablet (Drug); Placebo to match ketoconazole tablet (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Purdue Pharma LP

The purpose of this study is to assess the pharmacokinetics of buprenorphine and its metabolites in the presence and absence of ketoconazole.

Official title: A Single Center, Randomized, Double-Blind, Crossover Study to Assess Buprenorphine Accumulation and Description of Its Metabolites During Co-Medication of BTDS and Ketoconazole, Used As a CYP3A4 Inhibitor, in Healthy Subjects

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator)

Primary outcome:

AUCt of Buprenorphine With and Without Ketoconazole.

AUCinf of Buprenorphine With and Without Ketoconazole.

Cmax of Buprenorphine With and Without Ketoconazole.

AUCt of Nor-buprenorphine With and Without Ketoconazole

AUCinf of Nor-buprenorphine With and Without Ketoconazole

Cmax of Nor-buprenorphine With and Without Ketoconazole

AUCt of Nor-buprenorphine Glucuronide With and Without Ketoconazole

AUCinf of Nor-buprenorphine Glucuronide With and Without Ketoconazole

Cmax of Nor-buprenorphine Glucuronide With and Without Ketoconazole

AUCt of Buprenorphine-3-glucuronide With and Without Ketoconazole

AUCinf of Buprenorphine-3-glucuronide With and Without Ketoconazole

Cmax of Buprenorphine-3-glucuronide With and Without Ketoconazole

Secondary outcome:

CYP3A4 Inhibition by Observation of Plasma Nor-buprenorphine Production Assessed by the Erythromycin Breath Test.

The Number of Participants With Adverse Events (AEs) as a Measure of Safety.

Detailed description: To assess the pharmacokinetics of buprenorphine and its metabolites (nor-buprenorphine, buprenorphine 3 glucuronide and nor-buprenorphine glucuronide) in the presence and absence of ketoconazole. Safety evaluation of BTDS and ketoconazole in healthy subjects.

Minimum age: 18 Years. Maximum age: 54 Years. Gender(s): Both.

Criteria:

Inclusion Criteria Include:

- Males and females aged 18 to 54 years.

- Demonstrate CYP 3A4 inhibition by ketoconazole with the erythromycin breath test

(EBT) probe during the screening period.

- Female subjects who are surgically sterile or at least two years postmenopausal.

- Have a body weight ranging from 60 to 100 kilograms (kg), and are within 15% of

optimum for height and body frame, as determined from parameters of the Metropolitan Life Index.

- Agree not to use any medication, including over-the-counter (OTC) medications,

vitamins, mineral or herbal supplements, during the course of the study and for at least 7 days prior to the start of the study.

- Generally in good health as evidenced by lack of significant abnormal finding(s) in

medical history, physical examination, clinical laboratory tests, vital signs, and electrocardiogram (ECG).

- Willing to follow dietary restrictions, including abstention from grapefruit, herbal

dietary supplements especially those containing St. John's Wort, and caffeine containing products.

- Willing to refrain from strenuous exercise or contact sports during the study

Exclusion Criteria Include:

- Any history of hypersensitivity to buprenorphine, any excipient of BTDS,

ketoconazole, or other opioids, psychotropic or hypnotic drugs.

- Any medical or surgical conditions that might interfere with transdermal drug

absorption (eg skin lesions at site of application), gastrointestinal drug absorption (eg, delayed gastric emptying, malabsorption syndromes), distribution (eg, obesity), metabolism, or excretion (eg, hepatitis, glomerulonephritis).

- Any history of significant active medical illness such as:

- History or presence of liver disease or injury as indicated by increase of aspartate

transaminase (AST) or alanine transaminase (ALT) or bilirubin above the normal levels

- History or presence of renal insufficiency as indicated by abnormal creatinine or

blood urea nitrogen (BUN) or abnormal urinary constituent (eg, albumin).

- Any other clinically significant laboratory abnormalities.

- At risk of transmitting infection via blood samples such as:

- producing a positive human immunodeficiency virus (HIV) test at screening or having

participated in a high risk activity for contracting HIV

- producing a positive Hepatitis B surface antigen test at screening

- producing a positive Hepatitis C antibody test at screening.

- Any personal or family history of prolonged QT interval or disorders of cardiac

rhythm, including heartbeat below 45, unless agreed upon by sponsor.

- Females who are breastfeeding.

- Females with a positive serum or urine pregnancy test at screening or prior to

dosing, respectively. Other protocol-specific exclusion/inclusion criteria may apply.

Clinical Research Center, New Orleans, Louisiana 70119, United States

Product Information

Starting date: October 2002
Last updated: May 8, 2014