Healthy
Conditions
Keywords
Healthy subjects, Opioid, Transdermal
Brief summary
The purpose of this study is to determine the pharmacokinetics of BTDS following same-site patch reapplication after rest intervals.
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.
Interventions
Buprenorphine 10 mcg/hour patch applied transdermally for 7-day wear.
Sponsors
Purdue Pharma LP
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Period 1: AUC0-3d | 0 to 3 days (72 hours) | 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 \[The area under the plasma concentration-time course profile from time = 0 (dosing) through day 3 (to 72 hours)\]. |
| Period 2: AUC0-3d. | 0 to 3 days | 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). |
| Period 1: Cmax0-3d | 0 to 3 days | 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. |
| Period 2: Cmax0-3d | 0 to 3 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Period 1: Tmax0-7d. | 0 to 7days | 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. |
| Period 1: Cmax0-7 | 0 to 7 days | 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. |
| Period 2: Tmax0-7d. | 0 to 7 days | 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. |
| Period 1: AUC0-7d. | 0 to 7 days | 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. |
| Period 2: AUC0-7d | 0 to 7 days | 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. |
| Period 2: Cmax0-7d | 0 to 7 days | 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. |
Countries
United States
Participant flow
Recruitment details
19-Nov-2000 (first patient, first visit) to 18-Mar-2001 (last patient, last visit) at 1 center in the US, Columbus, OH.
Pre-assignment details
Subjects were assigned into 1 of 5 treatment groups with different recovery periods, ranging from 0 to 4 weeks. For the 5 treatment groups, the rest period was 0, 7, 14, 21, or 28 days, respectively, between the removal of the first buprenorphine transdermal system (BTDS) and placement of the second BTDS in exactly the same location.
Participants by arm
| Arm | Count |
|---|---|
| No Rest Each subject applied BTDS (10 mcg/h) on 2 occasions and wore it for 7 days (168 hours). Subjects were assigned to 1 of 5 treatment groups with different application site rest periods from 0 to 4 weeks. For this group, the rest period was 0 days between the removal of BTDS and placement of the second BTDS in the same location. | 13 |
| 7-Day Rest Each subject applied BTDS (10 mcg/h) on 2 occasions and wore it for 7 days (168 hours). Subjects were assigned to 1 of 5 treatment groups with different application site rest periods from 0 to 4 weeks. For this group, the rest period was 7 days between the removal of BTDS and placement of the second BTDS in the same location. | 14 |
| 14-Day Rest Each subject applied BTDS (10 mcg/h) on 2 occasions and wore it for 7 days (168 hours). Subjects were assigned to 1 of 5 treatment groups with different application site rest periods from 0 to 4 weeks. For this group, the rest period was 14 days between the removal of BTDS and placement of the second BTDS in the same location. | 15 |
| 21-Day Rest Each subject applied BTDS (10 mcg/h) on 2 occasions and wore it for 7 days (168 hours). Subjects were assigned to 1 of 5 treatment groups with different application site rest periods from 0 to 4 weeks. For this group, the rest period was 21 days between the removal of BTDS and placement of the second BTDS in the same location. | 14 |
| 28-Day Rest Each subject applied BTDS (10 mcg/h) on 2 occasions and wore it for 7 days (168 hours). Subjects were assigned to 1 of 5 treatment groups with different application site rest periods from 0 to 4 weeks. For this group, the rest period was 28 days between the removal of BTDS and placement of the second BTDS in the same location. | 14 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | No Rest | 7-Day Rest | 14-Day Rest | 21-Day Rest | 28-Day Rest |
|---|---|---|---|---|---|---|
| Age Continuous | 25.9 years STANDARD_DEVIATION 0.8 | 28.8 years STANDARD_DEVIATION 1.9 | 26.2 years STANDARD_DEVIATION 1.6 | 23.3 years STANDARD_DEVIATION 1.1 | 26.4 years STANDARD_DEVIATION 1.9 | 25.1 years STANDARD_DEVIATION 2.3 |
| Race/Ethnicity, Customized Asian | 7 participants | 3 participants | 0 participants | 1 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized Black or African American | 11 participants | 4 participants | 3 participants | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 2 participants | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White | 49 participants | 6 participants | 9 participants | 13 participants | 12 participants | 9 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 66 Participants | 11 Participants | 14 Participants | 14 Participants | 13 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 13 | 14 / 14 | 13 / 15 | 10 / 14 | 11 / 14 |
| serious Total, serious adverse events | 0 / 13 | 1 / 14 | 0 / 15 | 0 / 14 | 0 / 14 |
Outcome results
Primary
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 \[The area under the plasma concentration-time course profile from time = 0 (dosing) through day 3 (to 72 hours)\].
Time frame: 0 to 3 days (72 hours)
Population: Pharmacokinetic Population: All subjects who satisfied the inclusion/exclusion criteria, received both applications of BTDS, and submitted to postbaseline phlebotomy through at least the 72-hour time point of both applications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Rest | Period 1: AUC0-3d | 8680 pg/mL*h | Standard Error 920 |
| 7-Day Rest | Period 1: AUC0-3d | 7651 pg/mL*h | Standard Error 1514 |
| 14-Day Rest | Period 1: AUC0-3d | 6465 pg/mL*h | Standard Error 1091 |
| 21-Day Rest | Period 1: AUC0-3d | 12258 pg/mL*h | Standard Error 836 |
| 28-Day Rest | Period 1: AUC0-3d | 8890 pg/mL*h | Standard Error 1054 |
Primary
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.
Time frame: 0 to 3 days
Population: Pharmacokinetic Population: All subjects who satisfied the inclusion/exclusion criteria, received both applications of BTDS, and submitted to postbaseline phlebotomy through at least the 72-hour time point of both applications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Rest | Period 1: Cmax0-3d | 183 pg/mL | Standard Error 17 |
| 7-Day Rest | Period 1: Cmax0-3d | 193 pg/mL | Standard Error 50 |
| 14-Day Rest | Period 1: Cmax0-3d | 151 pg/mL | Standard Error 24 |
| 21-Day Rest | Period 1: Cmax0-3d | 241 pg/mL | Standard Error 15 |
| 28-Day Rest | Period 1: Cmax0-3d | 185 pg/mL | Standard Error 16 |
Primary
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).
Time frame: 0 to 3 days
Population: Pharmacokinetic Population: All subjects who satisfied the inclusion/exclusion criteria, received both applications of BTDS, and submitted to postbaseline phlebotomy through at least the 72-hour time point of both applications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Rest | Period 2: AUC0-3d. | 12316 pg/mL*h | Standard Error 1062 |
| 7-Day Rest | Period 2: AUC0-3d. | 14733 pg/mL*h | Standard Error 2255 |
| 14-Day Rest | Period 2: AUC0-3d. | 13571 pg/mL*h | Standard Error 1671 |
| 21-Day Rest | Period 2: AUC0-3d. | 12931 pg/mL*h | Standard Error 908 |
| 28-Day Rest | Period 2: AUC0-3d. | 9056 pg/mL*h | Standard Error 888 |
Primary
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.
Time frame: 0 to 3 days
Population: Pharmacokinetic Population: All subjects who satisfied the inclusion/exclusion criteria, received both applications of BTDS, and submitted to postbaseline phlebotomy through at least the 72-hour time point of both applications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Rest | Period 2: Cmax0-3d | 216 pg/mL | Standard Error 17 |
| 7-Day Rest | Period 2: Cmax0-3d | 300 pg/mL | Standard Error 52 |
| 14-Day Rest | Period 2: Cmax0-3d | 262 pg/mL | Standard Error 31 |
| 21-Day Rest | Period 2: Cmax0-3d | 278 pg/mL | Standard Error 41 |
| 28-Day Rest | Period 2: Cmax0-3d | 182 pg/mL | Standard Error 14 |
Secondary
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.
Time frame: 0 to 7 days
Population: Pharmacokinetic Population: All subjects who satisfied the inclusion/exclusion criteria, received both applications of BTDS, and submitted to postbaseline phlebotomy through at least the 72-hour time point of both applications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Rest | Period 1: AUC0-7d. | 21946 pg/mL*h | Standard Error 1686 |
| 7-Day Rest | Period 1: AUC0-7d. | 20541 pg/mL*h | Standard Error 2645 |
| 14-Day Rest | Period 1: AUC0-7d. | 14707 pg/mL*h | Standard Error 1851 |
| 21-Day Rest | Period 1: AUC0-7d. | 27040 pg/mL*h | Standard Error 1298 |
| 28-Day Rest | Period 1: AUC0-7d. | 22086 pg/mL*h | Standard Error 1591 |
Secondary
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.
Time frame: 0 to 7 days
Population: Pharmacokinetic Population: All subjects who satisfied the inclusion/exclusion criteria, received both applications of BTDS, and submitted to postbaseline phlebotomy through at least the 72-hour time point of both applications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Rest | Period 1: Cmax0-7 | 188 pg/mL | Standard Error 16 |
| 7-Day Rest | Period 1: Cmax0-7 | 206 pg/mL | Standard Error 48 |
| 14-Day Rest | Period 1: Cmax0-7 | 160 pg/mL | Standard Error 22 |
| 21-Day Rest | Period 1: Cmax0-7 | 245 pg/mL | Standard Error 14 |
| 28-Day Rest | Period 1: Cmax0-7 | 192 pg/mL | Standard Error 15 |
Secondary
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.
Time frame: 0 to 7days
Population: Pharmacokinetic Population: All subjects who satisfied the inclusion/exclusion criteria, received both applications of BTDS, and submitted to postbaseline phlebotomy through at least the 72-hour time point of both applications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Rest | Period 1: Tmax0-7d. | 74 hour | Standard Error 7 |
| 7-Day Rest | Period 1: Tmax0-7d. | 86 hour | Standard Error 6 |
| 14-Day Rest | Period 1: Tmax0-7d. | 78 hour | Standard Error 15 |
| 21-Day Rest | Period 1: Tmax0-7d. | 55 hour | Standard Error 6 |
| 28-Day Rest | Period 1: Tmax0-7d. | 76 hour | Standard Error 11 |
Secondary
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.
Time frame: 0 to 7 days
Population: Pharmacokinetic Population: All subjects who satisfied the inclusion/exclusion criteria, received both applications of BTDS, and submitted to postbaseline phlebotomy through at least the 72-hour time point of both applications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Rest | Period 2: AUC0-7d | 25126 pg/mL*h | Standard Error 2285 |
| 7-Day Rest | Period 2: AUC0-7d | 27543 pg/mL*h | Standard Error 3093 |
| 14-Day Rest | Period 2: AUC0-7d | 26174 pg/mL*h | Standard Error 2414 |
| 21-Day Rest | Period 2: AUC0-7d | 27123 pg/mL*h | Standard Error 1475 |
| 28-Day Rest | Period 2: AUC0-7d | 21790 pg/mL*h | Standard Error 1365 |
Secondary
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.
Time frame: 0 to 7 days
Population: Pharmacokinetic Population: All subjects who satisfied the inclusion/exclusion criteria, received both applications of BTDS, and submitted to postbaseline phlebotomy through at least the 72-hour time point of both applications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Rest | Period 2: Cmax0-7d | 216 pg/mL | Standard Error 17 |
| 7-Day Rest | Period 2: Cmax0-7d | 300 pg/mL | Standard Error 52 |
| 14-Day Rest | Period 2: Cmax0-7d | 262 pg/mL | Standard Error 31 |
| 21-Day Rest | Period 2: Cmax0-7d | 278 pg/mL | Standard Error 41 |
| 28-Day Rest | Period 2: Cmax0-7d | 202 pg/mL | Standard Error 18 |
Secondary
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.
Time frame: 0 to 7 days
Population: Pharmacokinetic Population: All subjects who satisfied the inclusion/exclusion criteria, received both applications of BTDS, and submitted to postbaseline phlebotomy through at least the 72-hour time point of both applications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Rest | Period 2: Tmax0-7d. | 42 hour | Standard Error 3 |
| 7-Day Rest | Period 2: Tmax0-7d. | 38 hour | Standard Error 6 |
| 14-Day Rest | Period 2: Tmax0-7d. | 36 hour | Standard Error 5 |
| 21-Day Rest | Period 2: Tmax0-7d. | 46 hour | Standard Error 4 |
| 28-Day Rest | Period 2: Tmax0-7d. | 63 hour | Standard Error 10 |