Buprenorphine Transdermal Patches Pharmacokinetic Study

Exclusion Criteria

• •Unstable condition of the primary disease of chronic pain, which, in the opinion of the investigator, would complicate the subject's participation in the study (e.g. require initiation of new medication).
• •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies).
• •History of seizures or at risk (i.e. head trauma, epilepsy in family, anamnesis, unclear loss of consciousness).
• •Any history of frequent nausea or emesis regardless of aetiology.
• •Malignancy or a history of malignancy.
• •History of orthostatic hypotension.
• •Subjects who have any medical or surgical conditions that might interfere with transdermal absorption, distribution, metabolism, or excretion of drugs.
• •Positive results for Hepatitis B surface antigen (HBsAg), Hepatitis C virus antibodies (HCV Ab), human immunodeficiency virus antibodies (HIVAb).
• •Urine screening before study is positive for opioids, barbiturates, amphetamines, cocaine metabolites, methadone, benzodiazepines, phencyclidine, methamphetamine, or cannabinoids or alcohol breath test is positive.
• •Subjects who have a current or past (within 5 years) history of substance or alcohol abuse, or subjects who, in the opinion of the investigator or the sub-investigator, have demonstrated addictive or substance abuse behaviors. Alcohol abuse is defined as regular alcohol consumption exceeding 14 drinks/week (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor).
• •Consumption of alcoholic beverages within 48 hours before patch application, and / or refusal to abstain from alcohol throughout the study until at least 48 hours after patch removal.
• •Use of tobacco- or nicotine-containing products in excess of the equivalent of 5 cigarettes per day.
• •Use of any medicinal product which inhibits CYP3A4 (e.g. troleandomycin, ketoconazole, gestodene, etc) or induces CYP3A4 (e.g. glucocorticoids, barbiturates, rifampicin,etc) within 4 weeks prior to first patch administration.
• •Subjects who are currently taking tricyclic antidepressants or have used tricyclic antidepressants within 4 weeks prior to the first patch administration.
• •Subjects taking monoamine oxidase (MAO) inhibiters within the past 14 days prior to the first patch administration
• •Subjects taking any opioid drug within the past 14 days prior to the first patch administration.
• •Use of prescription or nonprescription drugs, vitamins and dietary supplements within 7 days prior to the first patch administration. As an exception, acetaminophen could have been used at doses of ≤1 g/day.
• •Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days prior to the screening visit. Concurrent enrolment in another clinical trial is not permitted unless the sole purpose of the other trial is for collection of long-term follow-up/survival data.
• •Donated 400 mL or more of blood or blood products within 3 months prior to the start of the study.
• •Screening sitting blood pressure (BP) ≥140 mm Hg (systolic) or ≥ 90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is ≥140 mm Hg (systolic) or ≥ 90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to determine the subject's eligibility.
• •12-lead ECG demonstrating QTc\>450 msec or a QRS interval \>120 msec at Screening. If QTc exceeds 450 msec, or QRS interval exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS interval values should be used to determine the subject's eligibility.
• •Subjects who have history of hypersensitivity to opioid analgesic formulations.
• •Subjects who have history of hypersensitivity to naltrexone.
• •Subjects who have history of hypersensitivity to transdermal delivery system or patch adhesives.
• •Subjects with any potential dermatological disorder at a patch application site, e.g. previous and/or current unhealed extensive dermal damage in the area where the patch will be applied (e.g. dermatitis, burns, tattoos, scarring of the skin)
• •Subjects who could not discontinue therapy that involved direct heat sources (e.g. heat lamps, electric blankets, heating pads or heated water beds) for the duration of the study
• •Subjects with hairy areas who could not, or would not, cut the hair at the patch site for proper placement of the patch
• •Special diets such as caffeine or xanthine-containing foods and beverages (including pitaya fruit, mango, grapefruit, coffee, tea, cola, chocolate, grapefruit juice, etc.) should be taken within 48 hours before patch application or during the study.
• •Subjects who have difficulty swallowing tablets.
• •Subjects who cannot tolerate venipuncture, or subjects who have difficulty in collecting blood, or subjects who have a history of fainting at the sight of blood or needles.
• •Unwilling or suspected of not being able to comply with the study protocol.