A Single Center, Randomized, Double-Blind, Crossover Study to Assess Buprenorphine Accumulation and Description of Its Metabolites During Co-Medication of BTDS and Ketoconazole, Used As a CYP3A4 Inhibitor, in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- AUCt of Nor-buprenorphine Glucuronide With and Without Ketoconazole
研究概览
简要总结
The purpose of this study is to assess the pharmacokinetics of buprenorphine and its metabolites in the presence and absence of ketoconazole.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 54 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Sequence A
BTDS 10 with ketoconazole 200 mg tablets twice daily in period 1 and BTDS 10 with ketoconazole placebo tablets twice daily in period 2.
干预措施: Buprenorphine transdermal patch (Drug)
Sequence A
BTDS 10 with ketoconazole 200 mg tablets twice daily in period 1 and BTDS 10 with ketoconazole placebo tablets twice daily in period 2.
干预措施: Ketoconazole tablet (Drug)
Sequence A
BTDS 10 with ketoconazole 200 mg tablets twice daily in period 1 and BTDS 10 with ketoconazole placebo tablets twice daily in period 2.
干预措施: Placebo to match ketoconazole tablet (Drug)
Sequence B
BTDS 10 with ketoconazole placebo tablets twice daily in period 1 and BTDS 10 with ketoconazole 200 mg twice daily in period 2.
干预措施: Buprenorphine transdermal patch (Drug)
Sequence B
BTDS 10 with ketoconazole placebo tablets twice daily in period 1 and BTDS 10 with ketoconazole 200 mg twice daily in period 2.
干预措施: Ketoconazole tablet (Drug)
Sequence B
BTDS 10 with ketoconazole placebo tablets twice daily in period 1 and BTDS 10 with ketoconazole 200 mg twice daily in period 2.
干预措施: Placebo to match ketoconazole tablet (Drug)
结局指标
主要结局
AUCt of Nor-buprenorphine Glucuronide With and Without Ketoconazole
时间窗: 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
时间窗: 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.
时间窗: 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.
时间窗: 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.
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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)
- 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.)