Buprenorphine Accumulation and Description of Its Metabolites During Co-Medication of Buprenorphine Transdermal System (BTDS) and Ketoconazole
- Conditions
- Healthy
- Interventions
- Drug: Placebo to match ketoconazole tablet
- Registration Number
- NCT01259115
- Lead Sponsor
- Purdue Pharma LP
- Brief Summary
The purpose of this study is to assess the pharmacokinetics of buprenorphine and its metabolites in the presence and absence of ketoconazole.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Sequence A Placebo to match ketoconazole tablet 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 Placebo to match ketoconazole tablet BTDS 10 with ketoconazole placebo tablets twice daily in period 1 and BTDS 10 with ketoconazole 200 mg twice daily in period 2. Sequence A Buprenorphine transdermal patch 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 A Ketoconazole tablet 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 Buprenorphine transdermal patch BTDS 10 with ketoconazole placebo tablets twice daily in period 1 and BTDS 10 with ketoconazole 200 mg twice daily in period 2. Sequence B Ketoconazole tablet BTDS 10 with ketoconazole placebo tablets twice daily in period 1 and BTDS 10 with ketoconazole 200 mg twice daily in period 2.
- Primary Outcome Measures
Name Time Method AUCt of Nor-buprenorphine Glucuronide With and Without Ketoconazole BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.AUCinf of Nor-buprenorphine Glucuronide With and Without Ketoconazole BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.AUCt of Buprenorphine With and Without Ketoconazole. BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.AUCinf of Buprenorphine With and Without Ketoconazole. BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.Cmax of Buprenorphine With and Without Ketoconazole. BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.AUCt of Nor-buprenorphine With and Without Ketoconazole BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.AUCinf of Nor-buprenorphine With and Without Ketoconazole BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.Cmax of Nor-buprenorphine With and Without Ketoconazole BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.Cmax of Nor-buprenorphine Glucuronide With and Without Ketoconazole BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.AUCt of Buprenorphine-3-glucuronide With and Without Ketoconazole BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.AUCinf of Buprenorphine-3-glucuronide With and Without Ketoconazole BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.Cmax of Buprenorphine-3-glucuronide With and Without Ketoconazole BTDS Days 3, 10, 19, and 26; ketoconazole or placebo Days 9 and 25 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.
- Secondary Outcome Measures
Name Time Method CYP3A4 Inhibition by Observation of Plasma Nor-buprenorphine Production Assessed by the Erythromycin Breath Test. One time at screening and one time during ketoconazole treatment 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.
The Number of Participants With Adverse Events (AEs) as a Measure of Safety. The first day of study drug administration to 30 days after the last dose of study drug. 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 \[ECG\]).
Trial Locations
- Locations (1)
Clinical Research Center
🇺🇸New Orleans, Louisiana, United States