Clinical trial NCT03259958: A Bioequivalence Study of Corplex™ Donepezil Transdermal Delivery System Compared to Aricept®
Official title: A Study to Assess the Steady-State Bioequivalence of Once-Weekly Corplex™ 10mg Donepezil Transdermal Delivery System Compared to Daily Oral Administration of Aricept®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Corium, Inc.
Sponsor class: INDUSTRY
First posted: 2017-08-24
Enrollment: 86
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 study to assess the steady-state bioequivalence of once-weekly Corplex™ Donepezil 10 mg Transdermal Delivery System (TDS) compared to daily administration of Aricept®

Detailed description: Open label, randomized, 2-period, multiple-dose crossover study.

Approximately 86 healthy, adult male and female subjects will be enrolled.

Subjects will be randomized to 1 of 2 treatment sequences prior to the first study product treatment in treatment period 1.

For each treatment period; subjects will receive donepezil for 5 consecutive weeks. Blood samples for donepezil PK will be collected pre-dose through week 10.

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.
* 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;
  * Prolia;
  * 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 30 days prior to the first study drug administration
* Participation in another clinical study within 30 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: PK, AUC
timeFrame: Blood samples for donepezil PK will be collected pre dose until the end of each treatment period, approximately 10 weeks total
measure: PK, Cmax
timeFrame: Blood samples for donepezil PK will be collected pre dose until the end of each treatment period, approximately 10 weeks total
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Daily during 5 week treatment period and during the 5 week follow-on period
measure: PI assessment of local skin irritation response to TDS
timeFrame: 0.5hr, 24hr, 48hr and 72hr after each TDS removal. (5 consecutive weeks)
measure: PI assessment of TDS Adhesion
timeFrame: Daily during 5 week treatment period
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Celerion Inc.
state: Arizona
Study officials:
affiliation: Celerion
name: Danielle Armas, MD
role: PRINCIPAL_INVESTIGATOR
References: