Phase 1 Completed N=20 Randomized Double-blind

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

Healthy

Source: ClinicalTrials.gov NCT01259115 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jan 2011

Primary outcomePrimary: AUCt of Buprenorphine With and Without Ketoconazole. — 16354.8; 16627.9 pg/mL*h

Summary

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

Outcome Measures

Outcome	Result	p-value
PRIMARY AUCt of Buprenorphine With and Without Ketoconazole.	16354.8; 16627.9	—
PRIMARY AUCinf of Buprenorphine With and Without Ketoconazole.	18238.5; 19012.5	—
PRIMARY Cmax of Buprenorphine With and Without Ketoconazole.	142.2; 145.5	—
PRIMARY AUCt of Nor-buprenorphine With and Without Ketoconazole	5091.0; 3207.8	—
PRIMARY AUCinf of Nor-buprenorphine With and Without Ketoconazole	6767.9	—
PRIMARY Cmax of Nor-buprenorphine With and Without Ketoconazole	63.4; 44.6	—
PRIMARY AUCt of Nor-buprenorphine Glucuronide With and Without Ketoconazole	21376.9; 15840.5	—
PRIMARY AUCinf of Nor-buprenorphine Glucuronide With and Without Ketoconazole	17318.9	—
PRIMARY Cmax of Nor-buprenorphine Glucuronide With and Without Ketoconazole	218.2; 141.9	—
PRIMARY AUCt of Buprenorphine-3-glucuronide With and Without Ketoconazole	342.4	—
PRIMARY AUCinf of Buprenorphine-3-glucuronide With and Without Ketoconazole	—	—
PRIMARY Cmax of Buprenorphine-3-glucuronide With and Without Ketoconazole	88.5	—
SECONDARY CYP3A4 Inhibition by Observation of Plasma Nor-buprenorphine Production Assessed by the Erythromycin Breath Test.	64.49; 37.50; 64.50; 77.98	—
SECONDARY The Number of Participants With Adverse Events (AEs) as a Measure of Safety.	0; 0; 0; 0; 19; 16	—

Eligibility 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01259115). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.