Clinical trial NCT04617782: Pharmacokinetic Study of 5 and 10 mg Corplex™ Donepezil TDS Compared to 10 mg Aricept® in Healthy Volunteers
Official title: 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 TDS Compared to 10 mg Oral Aricept® in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Donepezil, Transdermal Delivery System
Lead sponsor: Corium, Inc.
Sponsor class: INDUSTRY
First posted: 2020-11-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Phase 1, open-label, randomized, 3-period, 3-treatment, crossover PK study to evaluate the steady-state pharmacokinetics
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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 QT (Fridericia) 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.

Primary outcomes:
measure: Maximum Concentration (Cmax)
timeFrame: 35 days of each Treatment
measure: Area Under the Curve (AUC)
timeFrame: 35 days each Treatment
Secondary outcomes:
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Worldwide Clinical Trials
state: Texas
Study officials:
affiliation: Worldwide Clinical Trials
name: Robert Bass, MD
role: PRINCIPAL_INVESTIGATOR
References: