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The purpose of this study is to assess the pharmacokinetics of buprenorphine and its metabolites in the presence and absence of ketoconazole.
To assess the pharmacokinetics of buprenorphine and its metabolites (nor-buprenorphine, buprenorphine 3 glucuronide and nor-buprenorphine glucuronide) in the presence and absence of ketoconazole.
Safety evaluation of BTDS and ketoconazole in healthy subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence A | Experimental | BTDS 10 with ketoconazole 200 mg tablets twice daily in period 1 and BTDS 10 with ketoconazole placebo tablets twice daily in period 2. |
|
| Sequence B | Experimental | BTDS 10 with ketoconazole placebo tablets twice daily in period 1 and BTDS 10 with ketoconazole 200 mg twice daily in period 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Buprenorphine transdermal patch | Drug | Buprenorphine 10 mcg/hour patch applied transdermally for 7-day wear. |
|
| Measure | Description | Time Frame |
|---|---|---|
| AUCt of Buprenorphine With and Without Ketoconazole. | AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration) of buprenorphine transdermal patch 10 with and without ketoconazole 200 mg oral twice daily. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or Ketoconazole placebo (orally twice daily) between days 17 and 27. | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| AUCinf of Buprenorphine With and Without Ketoconazole. | AUCinf (the area under the plasma-concentration time course profile from time 0 [dosing] to infinity) of buprenorphine transdermal patch 10 with and without ketoconazole 200 mg oral twice daily. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| Cmax of Buprenorphine With and Without Ketoconazole. | Cmax (maximum observed plasma concentration) of buprenorphine transdermal patch 10 with and without ketoconazole 200 mg oral tablets twice daily, Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| AUCt of Nor-buprenorphine With and Without Ketoconazole |
| Measure | Description | Time Frame |
|---|---|---|
| CYP3A4 Inhibition by Observation of Plasma Nor-buprenorphine Production Assessed by the Erythromycin Breath Test. | As part of subject screening, Erythromycin Breath Tests (EBT) were done on all potential subjects (enrolled population). CYP 3A4 inhibition was calculated by taking the difference of the baseline 14C erythromycin metabolism, subtracting the 14C erythromycin metabolism during ketoconazole treatment, dividing this difference by the baseline 14C erythromycin metabolism, and multiplying by 100 to express results in the form of percent inhibition. CYP3A4 inhibition was only done when subjects were on ketoconazole. |
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Inclusion Criteria Include:
Exclusion Criteria Include:
Other protocol-specific exclusion/inclusion criteria may apply.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research Center | New Orleans | Louisiana | 70119 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22845044 | Result | Kapil RP, Cipriano A, Michels GH, Perrino P, O'Keefe SA, Shet MS, Colucci SV, Noveck RJ, Harris SC. Effect of ketoconazole on the pharmacokinetic profile of buprenorphine following administration of a once-weekly buprenorphine transdermal system. Clin Drug Investig. 2012 Sep 1;32(9):583-92. doi: 10.1007/BF03261913. |
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Healthy male and female subjects aged 18 to 54 years, demonstrating successful inhibition of CYP3A4 using the EBT (erythromycin breath test) probe were randomized.
21-Oct-2002 (first subject, first visit) to 20-Jun-2003 (last subject, last visit). Study conducted at 1 site in New Orleans, LA.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence A: BTDS 10 With Ketoconazole (Test) First | Period 1: Buprenorphine transdermal system (BTDS) 10 with ketoconazole 200 mg tablets twice daily (Test) first; Washout Period of 4 to 18 days; Period 2: BTDS 10 with ketoconazole placebo tablets twice daily. |
| FG001 | Sequence B: BTDS 10 With Placebo (Reference) First |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
|
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| Ketoconazole tablet | Drug | Ketoconazole 200 mg tablets taken orally twice daily. |
|
| Placebo to match ketoconazole tablet | Drug | Placebo to match ketoconazole 200 mg tablets taken orally twice daily. |
|
For nor-buprenorphine pharmacokinetic metric, AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration). Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. |
| BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| AUCinf of Nor-buprenorphine With and Without Ketoconazole | For nor-buprenorphine pharmacokinetic metric, AUCinf (the area under the plasma-concentration time course profile from time 0 [dosing] to infinity). Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| Cmax of Nor-buprenorphine With and Without Ketoconazole | For nor-buprenorphine pharmacokinetic metric, Cmax (maximum observed plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| AUCt of Nor-buprenorphine Glucuronide With and Without Ketoconazole | For nor-buprenorphine glucuronide pharmacokinetic metrics, AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| AUCinf of Nor-buprenorphine Glucuronide With and Without Ketoconazole | For nor-buprenorphine glucuronide pharmacokinetic metrics, AUCinf (the area under the plasma-concentration time course profile from time 0 [dosing] to infinity) log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| Cmax of Nor-buprenorphine Glucuronide With and Without Ketoconazole | For nor-buprenorphine glucuronide pharmacokinetic metric, Cmax (maximum observed plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| AUCt of Buprenorphine-3-glucuronide With and Without Ketoconazole | For buprenorphine-3-glucuronide pharmacokinetic metric, AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| AUCinf of Buprenorphine-3-glucuronide With and Without Ketoconazole | For buprenorphine-3-glucuronide pharmacokinetic metric, AUCinf (the area under the plasma-concentration time course profile from time 0 [dosing] to infinity), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| Cmax of Buprenorphine-3-glucuronide With and Without Ketoconazole | For buprenorphine-3-glucuronide pharmacokinetic metric, Cmax (maximum observed plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
| One time at screening and one time during ketoconazole treatment |
| The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Safety assessments consisted of monitoring and recording medical history, physical examinations, vital signs (including temperature, heart rate, blood pressure and respiratory rate), reports of adverse experiences, and laboratory abnormalities (including electrocardiogram [ECG]). | The first day of study drug administration to 30 days after the last dose of study drug. |
Period 1: Buprenorphine transdermal system (BTDS) 10 with ketoconazole placebo tablets twice daily (Reference) first Washout Period of 4 to 18 days; Period 2: BTDS 10 with ketoconazole 200 mg tablets twice daily. |
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| NOT COMPLETED |
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| Period: Washout Period of 4 to 18 Days |
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| Period 2 |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study | Subjects received BTDS 10 with ketoconazole 200 mg or ketoconazole placebo tablets twice daily in period 1; Washout Period for 4 to 18 days; Subjects received BTDS 10 with ketoconazole 200 mg or ketoconazole placebo tablets twice daily in period 2. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | AUCt of Buprenorphine With and Without Ketoconazole. | AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration) of buprenorphine transdermal patch 10 with and without ketoconazole 200 mg oral twice daily. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or Ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid pharmacokinetic metric. | Posted | Mean | Standard Deviation | pg/mL*h | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
|
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| ||||||||||||||||||||||||||||
| Primary | AUCinf of Buprenorphine With and Without Ketoconazole. | AUCinf (the area under the plasma-concentration time course profile from time 0 [dosing] to infinity) of buprenorphine transdermal patch 10 with and without ketoconazole 200 mg oral twice daily. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid pharmacokinetic metric. | Posted | Mean | Standard Deviation | pg /mL•h | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
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| Primary | Cmax of Buprenorphine With and Without Ketoconazole. | Cmax (maximum observed plasma concentration) of buprenorphine transdermal patch 10 with and without ketoconazole 200 mg oral tablets twice daily, Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric. | Posted | Mean | Standard Deviation | pg/mL | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
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| Primary | AUCt of Nor-buprenorphine With and Without Ketoconazole | For nor-buprenorphine pharmacokinetic metric, AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration). Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric. | Posted | Mean | Standard Deviation | pg/mL*h | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
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| Secondary | CYP3A4 Inhibition by Observation of Plasma Nor-buprenorphine Production Assessed by the Erythromycin Breath Test. | As part of subject screening, Erythromycin Breath Tests (EBT) were done on all potential subjects (enrolled population). CYP 3A4 inhibition was calculated by taking the difference of the baseline 14C erythromycin metabolism, subtracting the 14C erythromycin metabolism during ketoconazole treatment, dividing this difference by the baseline 14C erythromycin metabolism, and multiplying by 100 to express results in the form of percent inhibition. CYP3A4 inhibition was only done when subjects were on ketoconazole. | Enrolled Population: All subjects who participated in the study. CYP3A4 Inhibition was only done when subjects were on Ketoconazole. | Posted | Mean | Standard Deviation | Percentage of participants | One time at screening and one time during ketoconazole treatment |
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| Primary | AUCinf of Nor-buprenorphine With and Without Ketoconazole | For nor-buprenorphine pharmacokinetic metric, AUCinf (the area under the plasma-concentration time course profile from time 0 [dosing] to infinity). Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric. | Posted | Mean | Standard Deviation | pg/mL*h | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
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| Primary | Cmax of Nor-buprenorphine With and Without Ketoconazole | For nor-buprenorphine pharmacokinetic metric, Cmax (maximum observed plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric. | Posted | Mean | Standard Deviation | pg/mL | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
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| Primary | AUCt of Nor-buprenorphine Glucuronide With and Without Ketoconazole | For nor-buprenorphine glucuronide pharmacokinetic metrics, AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric. | Posted | Mean | Standard Deviation | pg/mL*h | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
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| Primary | AUCinf of Nor-buprenorphine Glucuronide With and Without Ketoconazole | For nor-buprenorphine glucuronide pharmacokinetic metrics, AUCinf (the area under the plasma-concentration time course profile from time 0 [dosing] to infinity) log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric. | Posted | Mean | Standard Deviation | pg/mL*h | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
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| Primary | Cmax of Nor-buprenorphine Glucuronide With and Without Ketoconazole | For nor-buprenorphine glucuronide pharmacokinetic metric, Cmax (maximum observed plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric. | Posted | Mean | Standard Deviation | pg/mL | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
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| Primary | AUCt of Buprenorphine-3-glucuronide With and Without Ketoconazole | For buprenorphine-3-glucuronide pharmacokinetic metric, AUCt (area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric. | Posted | Mean | Standard Deviation | pg/mL*h | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
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| Primary | AUCinf of Buprenorphine-3-glucuronide With and Without Ketoconazole | For buprenorphine-3-glucuronide pharmacokinetic metric, AUCinf (the area under the plasma-concentration time course profile from time 0 [dosing] to infinity), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric. | Posted | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
|
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| Primary | Cmax of Buprenorphine-3-glucuronide With and Without Ketoconazole | For buprenorphine-3-glucuronide pharmacokinetic metric, Cmax (maximum observed plasma concentration), log transformed data were analyzed. Period 1, subjects wore BTDS 10 patch between days 3 and 10 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 1 and 11. Washout period of 4 to 18 days. Period 2, subjects wore BTDS 10 patch between days 19 and 26 and took ketoconazole (200 mg orally twice daily) or ketoconazole placebo (orally twice daily) between days 17 and 27. | The full analysis population for pharmacokinetics was defined as those subjects who received at least 1 dose of study drug and did not have any incidents of emesis for at least 12 hours from dosing during at least 1 period and had at least 1 valid PK metric. | Posted | Mean | Standard Deviation | pg/mL | BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 |
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| Secondary | The Number of Participants With Adverse Events (AEs) as a Measure of Safety. | Safety assessments consisted of monitoring and recording medical history, physical examinations, vital signs (including temperature, heart rate, blood pressure and respiratory rate), reports of adverse experiences, and laboratory abnormalities (including electrocardiogram [ECG]). | Safety Population: Safety analyses were performed on all subjects who received at least 1 dose of study drug and for whom at least 1 postdose safety observation was recorded. | Posted | Number | participants | The first day of study drug administration to 30 days after the last dose of study drug. |
|
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All adverse events during the course of the study were collected and were to be followed until resolution or for 30 days after the last dose of study drug. Serious adverse events were followed until the event resolved or sequelae stabilized.
AEs were learned of by spontaneous reports, subject interview, and daily diary
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BTDS With Ketoconazole | Subjects who were treated with buprenorphine transdermal patch 10 mcg/hour with ketoconazole 200 mg oral tablets twice daily. | 0 | 19 | 19 | 19 | ||
| EG001 | BTDS With Placebo | Subjects who were treated with buprenorphine transdermal patch 10 mcg/hour with ketoconazole placebo oral tablets twice daily. | 0 | 17 | 16 | 17 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiospasm | Gastrointestinal disorders | COSTART | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | COSTART | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | COSTART | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | COSTART | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | COSTART | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | COSTART | Systematic Assessment |
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| Tooth disorder | Gastrointestinal disorders | COSTART | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | COSTART | Systematic Assessment |
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| Abdominal pain | General disorders | COSTART | Systematic Assessment |
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| Back pain | General disorders | COSTART | Systematic Assessment |
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| Pain | General disorders | COSTART | Systematic Assessment |
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| Headache | General disorders | COSTART | Systematic Assessment |
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| Ecchymosis | Blood and lymphatic system disorders | COSTART | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | COSTART | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | COSTART | Systematic Assessment |
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| Creatinine increased | Metabolism and nutrition disorders | COSTART | Systematic Assessment |
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| Infection | Infections and infestations | COSTART | Systematic Assessment |
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| Accidental Injury | Injury, poisoning and procedural complications | COSTART | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | COSTART | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | COSTART | Systematic Assessment |
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| Dizziness | Nervous system disorders | COSTART | Systematic Assessment |
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| Somnolence | Nervous system disorders | COSTART | Systematic Assessment |
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| Pharyngitis | Respiratory, thoracic and mediastinal disorders | COSTART | Systematic Assessment |
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| Rhinitis | Respiratory, thoracic and mediastinal disorders | COSTART | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | COSTART | Systematic Assessment |
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| Erythema at site | Skin and subcutaneous tissue disorders | COSTART | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | COSTART | Systematic Assessment |
| |
| Pruritus at site | Skin and subcutaneous tissue disorders | COSTART | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | COSTART | Systematic Assessment |
| |
| Dry eyes | Eye disorders | COSTART | Systematic Assessment |
| |
| Photophobia | Eye disorders | COSTART | Systematic Assessment |
| |
| Urination impaired | Renal and urinary disorders | COSTART | Systematic Assessment |
| |
| Leukorrhea | Renal and urinary disorders | COSTART | Systematic Assessment |
| |
| Vasodilatation | Vascular disorders | COSTART | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Executive Medical Director, Clinical Pharmacology | Purdue Pharma L.P. | 800-733-1333 |
| ID | Term |
|---|---|
| D002047 | Buprenorphine |
| D007654 | Ketoconazole |
| ID | Term |
|---|---|
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
Not provided
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
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