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

Purdue Pharma LP20 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

DOUBLE

Enrollment

Conditions

Healthy

Interventions

Buprenorphine transdermal patchDRUG

Buprenorphine 10 mcg/hour patch applied transdermally for 7-day wear.

Ketoconazole tabletDRUG

Ketoconazole 200 mg tablets taken orally twice daily.

Placebo to match ketoconazole tabletDRUG

Placebo to match ketoconazole 200 mg tablets taken orally twice daily.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 54 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Clinical Research Center

New Orleans, Louisiana, United States

Outcomes

Primary Outcomes

AUCt of Buprenorphine With and Without Ketoconazole.

AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration) of buprenorphine transdermal patch 10 with and without ketoconazole 200 mg oral twice daily. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or Ketoconazole placebo (orally twice daily) between days 17 and 27.