Phase 1 Pharmacokinetic (PK) Study to Evaluate Once-weekly Corplex™ Donepezil Transdermal Delivery System Compared to Daily Oral Administration of Aricept® in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Corium, Inc.
- 入组人数
- 107
- 试验地点
- 1
- 主要终点
- Steady-state PK
研究概览
简要总结
A Phase 1, Randomized, Open-Label, 3-Way Crossover, Pilot, Pharmacokinetic Study to Evaluate the Steady State Pharmacokinetics of a Once-Weekly Application of Corplex Donepezil Transdermal Delivery System (TDS) Compared to Daily Oral Administration of Aricept in Healthy Adult Subjects
详细描述
Part A:
60 male and female subjects will be enrolled Subjects will receive 2 versions of once-weekly Corplex Donepezil TDS and QD oral Aricept; each administered for 35 days in 3 different treatment periods.
For each treatment period; Subjects will receive a lead-in dose of approximately 5 mg donepezil/day for 7 days before commencing a dose of 10 mg donepezil/day for 28 days. Blood samples for donepezil PK and red blood cell (RBC) AChEI (as a potential pharmacodynamic [PD] marker) will be collected pre-dose through Week 8.
Adhesion and skin irritation will be monitored throughout TDS Treatments. A washout period of at least 21 days between the last study drug administration (oral administration or removal of TDS, as appropriate) in each treatment period and the first application of TDS or oral drug administration, as appropriate, in the following treatment period.
Safety will be monitored throughout the study by adverse event reporting, repeated clinical and laboratory evaluations
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy, adult, Caucasian, male or female ≥18 years of age at screening
- •Body mass index ≥ 18.0 and ≤ 32.0 kg/m2 at screening
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms (ECGs), as deemed by the Investigator.
- •Have a Fitzpatrick skin type of I, II or III or have skin colorimeter scores equivalent to the allowed Fitzpatrick skin type.
排除标准
- •History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds (including piperidine derivatives and other cholinesterase inhibitors)
- •Has intolerance to venipuncture and/or inability to comply with the extensive blood sampling required for this study or does not have suitable veins in both arms
- •Potential for occupational exposure to anticholinesterase agents.
- •Female subjects with a positive pregnancy test or lactating
- •Positive urine drug or alcohol results
- •Estimated creatinine clearance in non-elderly subjects <80 mL/min at screening and in elderly subjects (i.e., ≥55 years of age) <60 mL/min at screening
- •Hemoglobin value of less than 11.5 g/dl for females, 13.0 g/dl for males at screening and first check-in
- •Any of the following drugs for 28 days prior to the first dose of study drug in Treatment Period 1 and throughout the study:
- •significant inducers of cytochrome P450 (CYP) enzymes and/or P-glycoprotein
- •anti-inflammatory drugs or cyclooxygenase 2 (COX-2) analgesic
- •beta-blockers;
- •anti-fungal medications;
- •anti-histamines;
- •cholinergics and anti-cholinergics;
- •oral corticosteroids;
- •Adjuvant analgesics
- •Muscle relaxants, anti-Parkinsonian or neuroleptic medications prior to the first dose of study drug
- •History or presence of excessive hairy skin on application sites as deemed by the Investigator to potentially interfere with drug absorption
- •History or presence of significant skin damage, diffuse skin diseases, scars, tattoos on the application sites or other skin disturbances as deemed by the Investigator to potentially interfere with drug absorption or irritation assessments
- •Use of donepezil hydrochloride or related drugs within 60 days prior to the first study drug administration
- •Participation in another clinical study within 60 days prior to the first study drug administration
- •Clinically significant depression symptoms or suicidal ideation or behavior as determined by the investigator:
研究组 & 干预措施
Donepezil TDS Version A
Lead-in of 5 mg/day donepezil of target dose (1 x Corplex 5 mg donepezil transdermal delivery system; 7 days) followed by; Target dose of 10 mg/day donepezil (Treatment A); Corplex 10 mg donepezil transdermal delivery system.
1x patch will be worn for 7 days. A total of 4 TDS patches will be applied for 4 consecutive 7 day periods.
干预措施: Donepezil TDS Version B (Drug)
Donepezil TDS Version A
Lead-in of 5 mg/day donepezil of target dose (1 x Corplex 5 mg donepezil transdermal delivery system; 7 days) followed by; Target dose of 10 mg/day donepezil (Treatment A); Corplex 10 mg donepezil transdermal delivery system.
1x patch will be worn for 7 days. A total of 4 TDS patches will be applied for 4 consecutive 7 day periods.
干预措施: Aricept (Drug)
Donepezil TDS Version B
Lead-in of 5 mg/day donepezil of target dose (1 x Corplex 5 mg donepezil transdermal delivery system; 7 days) followed by; Target dose of 10 mg/day donepezil (Treatment B); Corplex 10 mg donepezil delivery transdermal system.
1x patch will be worn for 7 days. A total of 4 TDS patches will be applied for 4 consecutive 7 day periods.
干预措施: Donepezil TDS Version A (Drug)
Donepezil TDS Version B
Lead-in of 5 mg/day donepezil of target dose (1 x Corplex 5 mg donepezil transdermal delivery system; 7 days) followed by; Target dose of 10 mg/day donepezil (Treatment B); Corplex 10 mg donepezil delivery transdermal system.
1x patch will be worn for 7 days. A total of 4 TDS patches will be applied for 4 consecutive 7 day periods.
干预措施: Aricept (Drug)
10 mg Aricept
5 mg/day oral Aricept, once daily for 7 days followed by; 10 mg/day Aricept once daily for 28 days
干预措施: Donepezil TDS Version A (Drug)
10 mg Aricept
5 mg/day oral Aricept, once daily for 7 days followed by; 10 mg/day Aricept once daily for 28 days
干预措施: Donepezil TDS Version B (Drug)
Donepezil TDS Version D
Target dose of 5 mg/day donepezil (Treatment D) Corplex 5 mg Donepezil TDS applied for a duration of 1 week.
干预措施: Donepezil TDS Version D (Drug)
Donepezil TDS Version D
Target dose of 5 mg/day donepezil (Treatment D) Corplex 5 mg Donepezil TDS applied for a duration of 1 week.
干预措施: Donepezil TDS Version E (Drug)
Donepezil TDS Version E
Target dose of 5 mg/day donepezil (Treatment E) Corplex 5 mg Donepezil TDS applied for a duration of 1 week
干预措施: Donepezil TDS Version D (Drug)
Donepezil TDS Version E
Target dose of 5 mg/day donepezil (Treatment E) Corplex 5 mg Donepezil TDS applied for a duration of 1 week
干预措施: Donepezil TDS Version E (Drug)
结局指标
主要结局
Steady-state PK
时间窗: TDS PK sampling time-points: Predose; Day 1 (hr0); Post-dose; Day 1 (hr2,6,12); Day 2-15,22 (hr0); Day 29 (hr0,3,6,12); Day 30-35 (hr0,12) Day 36 (hr0, 2,6,12); Day 37-38,41,44,47,50,54 (hr0);
To evaluate the steady-state PK of donepezil following once weekly Corplex Donepezil TDS application compared to once-daily (QD) oral administration of Aricept. Aricept PK sampling time points; Day 1 (hr0,1,2,3,4,6,8,12); Day 2,8,15,22,29 (hr0); Day 35(hr0,1,2,3,4,6,8,12); Day 36-37,40,43,46,49,53 (hr0)
PK (Part B)
时间窗: TDS PK sampling time-points: Predose; Day 1 (hr0); Post-dose; Day 1 (hr2,6,12); Day 2-8 (hr0,12); Day 9,10,11,13,16,19,22,26,30,36 (hr0)
To compare the PK of 2 once-weekly Corplex Donepezil TDS treatments (target dose 5 mg donepezil/day)
次要结局
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (Part A and B)(Daily during 36-day confinement period and 7 visits over the 21 day wash-out period.)
- PI assessment of local skin irritation response to TDS (Part A and B)(Part A: Daily during 36-day confinement period and 7 visits over the 21 day wash-out period. Part B:Daily during 10-day confinement period and 8 visits over the 28-35 day wash-out period.)
- PI assessment of TDS Adhesion per FDA UCM504157(Twice daily during 36-day confinement period)