Clinical trial NCT03432195: A Clinical Study to Evaluate the Pharmacokinetics (PK) of Corplex™ Donepezil Transdermal Delivery System (TDS) Applied to Different Body Locations
Official title: A Phase 1, Crossover Study to Evaluate the Pharmacokinetics of Corplex™ Donepezil 10 mg Transdermal Delivery System Applied to Different Body Locations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Corium, Inc.
Sponsor class: INDUSTRY
First posted: 2018-02-14
Enrollment: 66
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics, AUC
timeFrame: Blood samples for donepezil PK will be collected pre-dose until the end of each treatment period, approximately 18 weeks total
measure: Pharmacokinetics, CMAX
timeFrame: Blood samples for donepezil PK will be collected pre-dose until the end of each treatment period, approximately 18 weeks total
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Daily during 1 week treatment period throughout the 5 week period
measure: Summary Listing of Skin Irritation Score of Donepezil Corplex TDS by post-removal time point
timeFrame: 0.5hr, 24hr, 48hr and 72hr after each TDS removal. (3 days)
measure: Application Site Mean Adhesion Scores of Donepezil Corplex TDS
timeFrame: Daily during 1 week treatment period
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Celerion
name: Danielle Armas
role: PRINCIPAL_INVESTIGATOR
References: