Examine Plasma Concentrations of Buprenorphine Following Reapplication of Buprenorphine Transdermal System (BTDS) After Variable Application Site Rest Periods

Study Overview
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Brief Summary
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The purpose of this study is to determine the pharmacokinetics of BTDS following same-site patch reapplication after rest intervals.

Detailed Description
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The purpose of this study is to determine the minimum application site rest period that ensures that reapplication of BTDS 10 to the same site in the deltoid region does not result in increased absorption of drug in normal healthy subjects.

Official Title
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A Parallel Open-Label Study to Examine Plasma Concentrations of Buprenorphine Following Reapplication of 10-mg Buprenorphine Transdermal System (BTDS) After Variable Application Site Rest Periods in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Buprenorphine transdermal patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Include: Males and females 18 to 45 years of age, inclusive. Weight of 60 to 100 kilograms (kg) [132-220 pounds (lb)] and within 15% of optimum for height and body frame. In good health, evidenced by a lack of significantly abnormal findings on medical history, physical examination, clinical laboratory tests, vital signs, and electrocardiogram (ECG). Willing to discontinue and abstain from any medications, including vitamins or mineral supplements, throughout the study. Willing to follow dietary restrictions, including abstention from caffeine and xanthine-containing beverages for the duration of the study. Did not smoke or chew tobacco for at least 45 days prior to administration of study drugs, and agree not to use tobacco products during the study Exclusion Criteria Include: A history of hypersensitivity to opioid or psychotropic drugs. A history of recurrent seizures or syncope. Any medical or surgical conditions which might interfere with transdermal absorption, distribution, metabolism, or excretion of drugs. Any other significant active medical illness such as: history or presence of liver disease or liver injury that is indicated by an abnormal liver function profile such as aspartate transaminase (AST), alanine transaminase (ALT), or serum bilirubin; history or presence of impaired renal function that is indicated by abnormal creatinine or blood urea nitrogen (BUN) values or abnormal urinary constituents (eg, albuminuria); history of neutropenia (absolute neutrophil count [ANC] <1000/mm3 or thrombocytopenia (platelet <150,000/mm3). Positive results of urine drug screen or urine cotinine (consistent with active smoking). A history of substance or alcohol abuse within the past 5 years. Females who are nursing. Females who are pregnant as confirmed by a positive serum human chorionic gonadotropin (bHCG) test. Other protocol-specific exclusion/inclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No Rest<br>BTDS 10 with no application site rest period prior to application of second BTDS | Drug: Buprenorphine transdermal patch<br>* Buprenorphine 10 mcg/hour patch applied transdermally for 7-day wear.<br>* Other names: Butrans™;|
| Experimental: 7-Day Rest<br>BTDS 10 with 7-day rest period prior to application of second BTDS | Drug: Buprenorphine transdermal patch<br>* Buprenorphine 10 mcg/hour patch applied transdermally for 7-day wear.<br>* Other names: Butrans™;|
| Experimental: 14-Day Rest<br>BTDS 10 with 14-day rest period prior to application of second BTDS | Drug: Buprenorphine transdermal patch<br>* Buprenorphine 10 mcg/hour patch applied transdermally for 7-day wear.<br>* Other names: Butrans™;|
| Experimental: 21-Day Rest<br>BTDS 10 with 21-day rest period prior to application of second BTDS | Drug: Buprenorphine transdermal patch<br>* Buprenorphine 10 mcg/hour patch applied transdermally for 7-day wear.<br>* Other names: Butrans™;|
| Experimental: 28-Day Rest<br>BTDS 10 with 28-day rest period prior to application of second BTDS | Drug: Buprenorphine transdermal patch<br>* Buprenorphine 10 mcg/hour patch applied transdermally for 7-day wear.<br>* Other names: Butrans™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Period 1: AUC0-3d | Period 1 was the first application of BTDS 10: To determine the minimum application site rest periods that ensured that the reapplication of BTDS to the same site in the deltoid region did not result in increased absorption of the drug as measured by AUC0-3d [The area under the plasma concentration-time course profile from time = 0 (dosing) through day 3 (to 72 hours)]. | 0 to 3 days (72 hours) | 
| Period 2: AUC0-3d. | Period 2 was the second application of BTDS 10: To determine the minimum application site rest periods that ensured that the reapplication of BTDS to the same site in the deltoid region did not result in increased absorption of the drug as measured by AUC0-3d. AUC0-3d - The area under the plasma concentration-time course profile from time = 0 (dosing) through day 3 (to 72 hours). | 0 to 3 days | 
| Period 1: Cmax0-3d | Period 1 was the first application of BTDS 10: To determine the minimum application site rest periods that ensured that the reapplication of BTDS to the same site in the deltoid region did not result in increased absorption of the drug as measured by Cmax0-3d. Cmax0-3d - The maximum observed concentration taken directly from the plasma concentration-time course profile from time = 0 (dosing) through day 3 (to 72 hours). This was considered an index of maximum (peak) exposure to the study drug. | 0 to 3 days | 
| Period 2: Cmax0-3d | Period 2 was the second application of BTDS 10: To determine the minimum application site rest periods that ensured that the reapplication of BTDS to the same site in the deltoid region did not result in increased absorption of the drug as measured by Cmax0-3d. Cmax0-3d (pg/mL) - The maximum observed concentration taken directly from the plasma concentration-time course profile from time = 0 (dosing) through day 3 (to 72 hours). This was considered an index of maximum (peak) exposure to the study drug. | 0 to 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Period 1: AUC0-7d. | Period 1 was the first application of BTDS 10: The time for absorption to return to normal measured by AUC0-7d. AUC0-7d - The area under the plasma concentration-time course profile from time = 0 (dosing) to BTDS removal. | 0 to 7 days | 
| Period 2: AUC0-7d | Period 2 was the second application of BTDS 10: The time for absorption to return to normal measured by AUC0-7d. AUC0-7d - The area under the plasma concentration-time course profile from time = 0 (dosing) to BTDS removal. | 0 to 7 days | 
| Period 1: Cmax0-7 | Period 1 was the first application of BTDS 10: The time for absorption to return to normal measured by Cmax0-7. Cmax0-7d - The maximum observed concentration taken directly from the plasma concentration-time course profile. | 0 to 7 days | 
| Period 2: Cmax0-7d | Period 2 was the second application of BTDS 10: The time for absorption to return to normal measured by Cmax0-7d. Cmax0-7d - The maximum observed concentration taken directly from the plasma concentration-time course profile. | 0 to 7 days | 
| Period 1: Tmax0-7d. | Period 1 was the first application of BTDS 10: The time for absorption to return to normal measured by Tmax0-7d. Tmax0-7d - The time from dosing to the maximum observed concentration was taken directly from the plasma concentration-time course profile. If the maximum plasma concentration was observed at 2 or more consecutive time points, the earliest time point was used for Tmax. | 0 to 7days | 
| Period 2: Tmax0-7d. | Period 2 was the second application of BTDS 10: The time for absorption to return to normal measured by Tmax0-7d. Tmax0-7d - The time from dosing to the maximum observed concentration was taken directly from the plasma concentration-time course profile. If the maximum plasma concentration was observed at 2 or more consecutive time points, the earliest time point was used for Tmax. | 0 to 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy subjects, Opioid, Transdermal