Clinical trial NCT02968719: A Phase 1, Corplex™ Donepezil Transdermal System Compared to Oral Aricept®
Official title: Phase 1 Pharmacokinetic (PK) Study to Evaluate Once-weekly Corplex™ Donepezil Transdermal Delivery System Compared to Daily Oral Administration of Aricept® in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: Corium, Inc.
Sponsor class: INDUSTRY
First posted: 2016-11-21
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: A Phase 1, Randomized, Open-Label, 3-Way Crossover, Pilot, Pharmacokinetic Study to Evaluate the Steady State Pharmacokinetics of a Once-Weekly Application of Corplex Donepezil Transdermal Delivery System (TDS) Compared to Daily Oral Administration of Aricept in Healthy Adult Subjects

Detailed description: Part A:

60 male and female subjects will be enrolled Subjects will receive 2 versions of once-weekly Corplex Donepezil TDS and QD oral Aricept; each administered for 35 days in 3 different treatment periods.

For each treatment period; Subjects will receive a lead-in dose of approximately 5 mg donepezil/day for 7 days before commencing a dose of 10 mg donepezil/day for 28 days. Blood samples for donepezil PK and red blood cell (RBC) AChEI (as a potential pharmacodynamic \[PD\] marker) will be collected pre-dose through Week 8.

Adhesion and skin irritation will be monitored throughout TDS Treatments. A washout period of at least 21 days between the last study drug administration (oral administration or removal of TDS, as appropriate) in each treatment period and the first application of TDS or oral drug administration, as appropriate, in the following treatment period.

Safety will be monitored throughout the study by adverse event reporting, repeated clinical and laboratory evaluations

Part B:

Up to 47 subjects male and/or female will be enrolled This is an open-label, randomized, 2-way crossover sub-study. Eligible subjects will be randomized to 1 of 2 treatment sequences prior to the first TDS application.

Subjects will receive 2 different once-weekly Corplex Donepezil TDS treatments (Treatments D and E), each administered for 1 week, in 2 different treatment periods (Treatment Period 1 and Treatment Period 2).

In each treatment period, subjects will receive a target dose of 5 mg donepezil/day for 7 days. There will be a washout period of 35 days between removal of the first TDS in Treatment Period 1 and application of the second TDS in Treatment Period 2.

Blood samples for donepezil PK will be collected pre-dose and through to Week 6 of each treatment period.

Safety will be monitored throughout the sub-study by repeated clinical, skin irritation and laboratory evaluations.

Eligibility criteria: Inclusion Criteria:

* Healthy, adult, Caucasian, male or female ≥18 years of age at screening
* 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 60 days prior to the first study drug administration
* Participation in another clinical study 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: Steady-state PK
timeFrame: TDS PK sampling time-points: Predose; Day 1 (hr0); Post-dose; Day 1 (hr2,6,12); Day 2-15,22 (hr0); Day 29 (hr0,3,6,12); Day 30-35 (hr0,12) Day 36 (hr0, 2,6,12); Day 37-38,41,44,47,50,54 (hr0);
measure: PK (Part B)
timeFrame: TDS PK sampling time-points: Predose; Day 1 (hr0); Post-dose; Day 1 (hr2,6,12); Day 2-8 (hr0,12); Day 9,10,11,13,16,19,22,26,30,36 (hr0)
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (Part A and B)
timeFrame: Daily during 36-day confinement period and 7 visits over the 21 day wash-out period.
measure: PI assessment of local skin irritation response to TDS (Part A and B)
timeFrame: Part A: Daily during 36-day confinement period and 7 visits over the 21 day wash-out period. Part B:Daily during 10-day confinement period and 8 visits over the 28-35 day wash-out period.
measure: PI assessment of TDS Adhesion per FDA UCM504157
timeFrame: Twice daily during 36-day confinement period
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Celerion
name: Danielle Armas, MD
role: PRINCIPAL_INVESTIGATOR
References: