Buprenorphine Accumulation and Description of Its Metabolites During Co-Medication of Buprenorphine Transdermal System (BTDS) and Ketoconazole
Condition: Healthy
Intervention: Buprenorphine transdermal patch; Ketoconazole tablet; Placebo to match ketoconazole tablet
Intervention description: Buprenorphine 10 mcg/hour patch applied transdermally for 7-day wear.; Ketoconazole 200 mg tablets taken orally twice daily.; Placebo to match ketoconazole 200 mg tablets taken orally twice daily.
Intervention MeSH terms: Ketoconazole; Buprenorphine
Phase: Phase 1
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 54 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy subjects; Opioid; Transdermal

Summary:

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

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.