Crossover Pharmacokinetic (PK) Study of 5 and 10 mg Corplex™ Donepezil TDS Compared to 10 mg Aricept® in Healthy Volunteers

A Phase 1, Open-Label, 3-Period, Randomized, Crossover Pharmacokinetic Study to Evaluate the Steady-State Pharmacokinetics of 5 mg and 10 mg Corplex™ Donepezil Transdermal Delivery Systems Compared to 10 mg Oral Administration of Aricept® in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Combination product: Donepezil TDS; Drug: Aricept

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 QTcF 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; 5 mg/day Donepezil Transdermal Delivery System (TDS) 1-week wear and applied weekly for 5 consecutive weeks	Combination product: Donepezil TDS; Transdermal Delivery System
Experimental: Treatment B; 10 mg/day Donepezil TDS 1-week wear and applied weekly for 5 consecutive weeks	Combination product: Donepezil TDS; Transdermal Delivery System
Active Comparator: Treatment C; 10 mg/day Aricept® donepezil tablet administered QD for 5 consecutive weeks	Drug: Aricept; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steady State Bioequivalence of 10 mg/day donepezil	To evaluate steady-state donepezil plasma exposure following once-weekly treatments with 10 mg/day Corplex™ Donepezil TDS compared to once-daily oral administration of 10 mg Aricept®	35 days of Treatment of each comparator

Collaborators and Investigators

• Sponsor: Corium, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Actual): April 5, 2021
• Study Completion (Actual): April 5, 2021

Study Registration Dates

• First Submitted: November 1, 2020
• First Submitted That Met QC Criteria: November 1, 2020
• First Posted (Actual): November 5, 2020

Study Record Updates

• Last Update Posted (Actual): May 21, 2021
• Last Update Submitted That Met QC Criteria: May 20, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Donepezil, Transdermal Delivery System
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: CL-P-20003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No