A Phase I, Open-Label, Three-Period, Fixed-Sequence Study To Estimate The Steady-State Effect Of Ketoconazole And Omeprazole On The Single-Dose Pharmacokinetics Of Dimebon [PF-01913539] In Healthy CYP2D6 EM And PM Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Dimebon alone: Dimebon PK in CYP2D6 EMs and PMs (Cmax, Tmax, AUCinf (as data permit), AUClast, and t1/2 (as data permit), CL/F (as data permit) and V/F (as data permit))
研究概览
简要总结
This study will evaluate the potential for a drug-drug interaction of Dimebon with ketoconazole and omeprazole, potent inhibitors of the drug metabolizing enzymes CYP3A4 and CYP2C19, respectively.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Subjects must have either a CYP2D6 EM (n=12) or PM (n=12) status based on genotyping at screening.
- •Subjects must have a CYP2C19 EM status based on status at screening.
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
- •Subjects with any history of a previous seizure or convulsion or significant head trauma.
- •Subjects specifically allergic to imidazole antifungal agents.
- •Subjects specifically allergic to omeprazole or other proton pump inhibitors.
- •Any condition possibly affecting drug absorption (eg, gastrectomy).
- •Subjects with hypersensitivity reactions to Dimebon or other antihistamines.
- •Consumption of grapefruit or grapefruit containing products within 7 days prior to the first dose of study medication.
- •Subjects currently taking omeprazole, other proton pump inhibitors, antacids, H2-blockers or CYP2C19 inhibitors.
- •Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of nonhormonal contraception as outlined in this protocol from at least 14 days prior to the first dose of study medication.
研究组 & 干预措施
Period 1
干预措施: Dimebon alone (Drug)
Period 2
干预措施: Dimebon + Ketoconazole (Drug)
Period 3
干预措施: Dimebon + Omeprazole (Drug)
结局指标
主要结局
Dimebon alone: Dimebon PK in CYP2D6 EMs and PMs (Cmax, Tmax, AUCinf (as data permit), AUClast, and t1/2 (as data permit), CL/F (as data permit) and V/F (as data permit))
时间窗: Period 1 Day 1
Dimebon + keto: Dimebon PK in CYP2D6 EMs and PMs (Cmax, Tmax, AUCinf (as data permit), AUClast, and t1/2 (as data permit), CL/F (as data permit) and V/F (as data permit))
时间窗: Period 2 Day 4
Dimebon + omeprazole: Dimebon PK in CYP2D6 EMs and PMs (Cmax, Tmax, AUCinf (as data permit), AUClast, and t1/2 (as data permit), CL/F (as data permit) and V/F (as data permit))
时间窗: Period 3 Day 5
次要结局
- Dimebon alone: Safety and tolerability (AE's, ECG, vital signs, safety labs)(Period 1 Day 1-7)
- Dimebon + keto: Safety and tolerability (AE's, ECG, vital signs, safety labs)(Period 2 Day 1-12)
- Dimebon + omeprazole: Safety and tolerability (AE's, ECG, vital signs, safety labs)(Period 3 Day 1-13)