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

NCT ID: NCT01259115

Last Updated: 2014-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-10-31
• Study Completion Date: 2003-06-30

Brief Summary

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

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: DOUBLE

Study Groups

Sequence A

BTDS 10 with ketoconazole 200 mg tablets twice daily in period 1 and BTDS 10 with ketoconazole placebo tablets twice daily in period 2.

Group Type: EXPERIMENTAL

Buprenorphine transdermal patch

Intervention Type: DRUG

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

Ketoconazole tablet

Intervention Type: DRUG

Ketoconazole 200 mg tablets taken orally twice daily.

Placebo to match ketoconazole tablet

Intervention Type: DRUG

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

Sequence B

BTDS 10 with ketoconazole placebo tablets twice daily in period 1 and BTDS 10 with ketoconazole 200 mg twice daily in period 2.

Group Type: EXPERIMENTAL

Buprenorphine transdermal patch

Intervention Type: DRUG

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

Ketoconazole tablet

Intervention Type: DRUG

Ketoconazole 200 mg tablets taken orally twice daily.

Placebo to match ketoconazole tablet

Intervention Type: DRUG

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

Interventions

Buprenorphine transdermal patch

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

Intervention Type: DRUG

Ketoconazole tablet

Ketoconazole 200 mg tablets taken orally twice daily.

Intervention Type: DRUG

Placebo to match ketoconazole tablet

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

Intervention Type: DRUG

Other Intervention Names

Butrans™

Eligibility Criteria

Inclusion Criteria

• 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

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 54 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Purdue Pharma LP

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinical Research Center

New Orleans, Louisiana, United States

Countries

United States

References

Kapil RP, Cipriano A, Michels GH, Perrino P, O'Keefe SA, Shet MS, Colucci SV, Noveck RJ, Harris SC. Effect of ketoconazole on the pharmacokinetic profile of buprenorphine following administration of a once-weekly buprenorphine transdermal system. Clin Drug Investig. 2012 Sep 1;32(9):583-92. doi: 10.1007/BF03261913.

Reference Type: RESULT

PMID: 22845044 (View on PubMed)

Other Identifiers

BUP1009

Identifier Type: -

Identifier Source: org_study_id