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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Buprenorphine transdermal patch

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Department of Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Purdue Pharma LP

Publications and helpful links

Helpful Links

• Product Information

Study record dates

Study Major Dates

• Study Start: November 1, 2000
• Primary Completion (Actual): March 1, 2001
• Study Completion (Actual): March 1, 2001

Study Registration Dates

• First Submitted: December 10, 2010
• First Submitted That Met QC Criteria: December 10, 2010
• First Posted (Estimate): December 13, 2010

Study Record Updates

• Last Update Posted (Estimate): September 3, 2012
• Last Update Submitted That Met QC Criteria: August 27, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Transdermal; Opioid; Healthy subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: BUP1002