Alzheimer's Disease
Conditions
Brief summary
A Phase 1, Crossover Study to Evaluate the Pharmacokinetics of Corplex™ Donepezil 10 mg Transdermal Delivery System Applied to Different Body Locations
Detailed description
Randomized, open-label, 3-way crossover study Up to 66 healthy, adult male and female subjects will be enrolled. All subjects will receive Corplex Donepezil TDS patches applied to 3 different locations on each subject (back, buttock, and leg) during 3 different, consecutive treatment periods. For each subject, the location of product administration during each treatment period will be randomized. During each treatment period, all subjects will receive a once-weekly 10 mg TDS, target dose 10 mg donepezil/day, applied for 7 days (1 week) on either the back, buttock, or leg in accordance with the randomized treatment location for that treatment period. Blood samples for donepezil PK will be collected pre-dose until the end of each treatment period. The PK sample collection time points are as follows: Week 1: Pre-TDS application prior to 0 hour and post-TDS application at 2, 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 hours. Week 2: Pre-Week 1 TDS removal at 168 hours, and post-TDS removal at up to 528 hours Adhesion and skin irritation will be monitored throughout TDS treatments. Safety will be monitored throughout the study by adverse event reporting, repeated clinical and laboratory evaluations.
Interventions
DRUGDonepezil TDS
Donepezil Hydrochloride Transdermal Delivery System
Sponsors
Corium, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy, adult, male or female * 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 Key
Exclusion criteria
* 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 * 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 * Muscle relaxants, anti-Parkinsonian or neuroleptic medications prior to the first dose of study drug * History or presence of significant skin damage or other skin disturbances as deemed by the Investigator to potentially interfere with patch procedures * Use of donepezil hydrochloride or related drugs within 60 days prior to the first study drug administration * Clinically significant depression symptoms or suicidal ideation or behavior as determined by the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics, AUC | Blood samples for donepezil PK will be collected pre-dose until the end of each treatment period, approximately 18 weeks total | Area under the plasma concentration versus time curve (AUC) of once-weekly Corplex Donepezil TDS applied to different body locations. |
| Pharmacokinetics, CMAX | Blood samples for donepezil PK will be collected pre-dose until the end of each treatment period, approximately 18 weeks total | Peak Plasma Concentration (Cmax) of once-weekly Corplex Donepezil TDS applied to different body locations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Daily during 1 week treatment period throughout the 5 week period | General Safety (adverse events and serious adverse events as reported by subject following guidance CTCAE v4.0) |
| Summary Listing of Skin Irritation Score of Donepezil Corplex TDS by post-removal time point | 0.5hr, 24hr, 48hr and 72hr after each TDS removal. (3 days) | Skin irritation score is determined by the sum of Dermal Response score (8-point categorical scale; where 0=no evidence of irritation to 7=strong reaction) using numeric values) and the Other Effects score (6-point categorical scale where 0=none observed to H=scabs/erosion using alphabet letters equivalent to numeric values) and summarized by application site (back, buttock and leg) |
| Application Site Mean Adhesion Scores of Donepezil Corplex TDS | Daily during 1 week treatment period | Adhesion score is collected using a 12-point categorical scale, where 0=100% adhered to 11=detached |
Countries
United States
Outcome results
None listed