Healthy Subjects
Conditions
Keywords
Donepezil, Transdermal Delivery System
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.
Interventions
COMBINATION_PRODUCTDonepezil TDS
Transdermal Delivery System
DRUGAricept
Oral
Sponsors
Corium, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Masking description
open label
Intervention model description
Phase 1, open-label, randomized, 3-period, 3-treatment, crossover PK study to evaluate the steady-state pharmacokinetics
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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 1. systolic blood pressure outside the range of 90-145 mmHg, or 2. diastolic blood pressure outside the range of 50-90 mmHg, or 3. 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 m2. * Prolonged corrected QT (Fridericia) 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 * Use of donepezil hydrochloride or related drugs within 60 days prior to the first study drug administration. * Has participated in another clinical trial within 30 days prior to Day -1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) | 35 days of each Treatment | To evaluate steady-state donepezil plasma exposure (Cmax) following 5 weeks of treatment. |
| Area Under the Curve (AUC) | 35 days each Treatment | To evaluate steady-state donepezil plasma exposure (AUC) following 5 weeks of treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants were assigned to receive treatment sequence ABC or ACB in a crossover fashion.
Treatment A: 5 mg/day Donepezil TDS 1-week wear and applied weekly for 5 consecutive weeks, then 1 day washout; Treatment B: 10 mg/day Donepezil TDS 1-week wear and applied weekly for 5 consecutive weeks, then 1 day washout; Treatment C: 10 mg/day Aricept® donepezil tablet administered QD for 5 consecutive weeks, then 1 day washout; | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment A - 5 mg TDS | failure to follow site rules | 1 |
| Treatment A - 5 mg TDS | Physician Decision | 2 |
| Treatment B - 10 mg TDS | Protocol Violation | 1 |
| Treatment B - 10 mg TDS | Withdrawal by Subject | 1 |
| Treatment C - 10 mg Oral | failure to follow site rules | 1 |
| Treatment C - 10 mg Oral | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 39.8 years STANDARD_DEVIATION 9.91 |
| Race/Ethnicity, Customized Race Asian | 1 Participants |
| Race/Ethnicity, Customized Race Black of African American | 3 Participants |
| Race/Ethnicity, Customized Race White | 56 Participants |
| Region of Enrollment United States | 60 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 55 | 0 / 56 |
| other Total, other adverse events | 32 / 60 | 30 / 55 | 32 / 56 |
| serious Total, serious adverse events | 0 / 60 | 0 / 55 | 0 / 56 |
Outcome results
Primary
Area Under the Curve (AUC)
To evaluate steady-state donepezil plasma exposure (AUC) following 5 weeks of treatment
Time frame: 35 days each Treatment
Population: all subjects without major protocol deviations that could affect PK and who had at least one PK parameter derived
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A 5 mg TDS | Area Under the Curve (AUC) | 4366.0 AUC h*ng/mL | Standard Deviation 1380.1 |
| Treatment B 10 mg TDS | Area Under the Curve (AUC) | 9099.0 AUC h*ng/mL | Standard Deviation 2972.1 |
| Treatment C 10 mg Oral | Area Under the Curve (AUC) | 8462.6 AUC h*ng/mL | Standard Deviation 2558 |
Primary
Maximum Concentration (Cmax)
To evaluate steady-state donepezil plasma exposure (Cmax) following 5 weeks of treatment.
Time frame: 35 days of each Treatment
Population: all subjects without major protocol deviations that could affect PK and who had at least one PK parameter derived
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A 5 mg TDS | Maximum Concentration (Cmax) | 29.9 Cmax ng/ml | Standard Deviation 9.1 |
| Treatment B 10 mg TDS | Maximum Concentration (Cmax) | 62.4 Cmax ng/ml | Standard Deviation 19.9 |
| Treatment C 10 mg Oral | Maximum Concentration (Cmax) | 70.5 Cmax ng/ml | Standard Deviation 19.4 |