A Phase 1, Open-Label, 3-Period, Randomized, Crossover Pharmacokinetic Study to Evaluate the Steady-State Pharmacokinetics of 5 mg and 10 mg Corplex™ Donepezil Transdermal Delivery Systems Compared to 10 mg Oral Administration of Aricept® in Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- Donepezil TDS
- Conditions
- Healthy Subjects
- Sponsor
- Corium, Inc.
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Maximum Concentration (Cmax)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
Phase 1, open-label, randomized, 3-period, 3-treatment, crossover pharmacokinetic study to evaluate the steady-state pharmacokinetics of 5 mg/day and 10 mg/day Corplex™ Donepezil TDS manufactured with the commercial process compared to 10 mg Aricept® in healthy volunteers.
Detailed Description
Screening Period: Subjects will undergo a Screening Period up to 28 days prior to entering the Treatment Phase. Treatment Phase consisting of 3 Treatment periods with 3 Treatments A, B, C. Treatment Period 1: All Subjects will receive Treatment A; 5 mg/day Donepezil Transdermal Delivery System (TDS); 1-week wear and applied for 5 consecutive weeks. Treatment Periods 2 and 3: Subjects will be randomized (by gender) to receive either sequences of Treatments B-C or Treatments C-B. Treatment B: 10 mg/day Donepezil TDS 1-week wear and applied weekly for 5 consecutive weeks Treatment C: 10 mg/day Aricept® donepezil tablet administered daily (QD) for 5 weeks. Blood samples for pharmacokinetics and safety assessments will be collected during the Treatment Phase.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy males and females.
- •Subject's Body Mass Index (BMI) must be between 18 and 32 kg/m2 (inclusive).
- •Subject must be continuous non-smokers.
- •Subject must have a Fitzpatrick skin type of I, II or III.
Exclusion Criteria
- •History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
- •After resting seated for at least 3 minutes, subjects should be excluded from the study with the following vital signs at Screening
- •systolic blood pressure outside the range of 90-145 mmHg, or
- •diastolic blood pressure outside the range of 50-90 mmHg, or
- •resting heart rate outside the range of 40-100 beats per minute.
- •Has an isolated ALT ≥1.5x the ULN or AST ≥1.5x the ULN at Screening; or both ALT and AST exceeding the ULN.
- •Estimated creatinine clearance at screening \<70 mL/min/1.73 m
- •Prolonged corrected QTcF on screening ECG (≥450 ms for both females and males).
- •History or presence of excessive hairy skin on application sites as deemed by the Investigator to potentially interfere with patch adhesion or 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 skin tolerability assessments
Arms & Interventions
Treatment A
5 mg/day Donepezil Transdermal Delivery System (TDS) 1-week wear and applied weekly for 5 consecutive weeks
Intervention: Donepezil TDS
Treatment B
10 mg/day Donepezil TDS 1-week wear and applied weekly for 5 consecutive weeks
Intervention: Donepezil TDS
Treatment C
10 mg/day Aricept® donepezil tablet administered QD for 5 consecutive weeks
Intervention: Aricept
Outcomes
Primary Outcomes
Maximum Concentration (Cmax)
Time Frame: 35 days of each Treatment
To evaluate steady-state donepezil plasma exposure (Cmax) following 5 weeks of treatment.
Area Under the Curve (AUC)
Time Frame: 35 days each Treatment
To evaluate steady-state donepezil plasma exposure (AUC) following 5 weeks of treatment