CompletedNCT04617782Updated Sep 19, 2024Results posted

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

A Phase 1 interventional study of Donepezil TDS and Aricept in Healthy Subjects, sponsored by Corium, Inc.. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-09-19.

Sponsored by Corium, Inc. · Phase 1, Interventional, and Other

Phase: Phase 1
Study type: Interventional
Enrollment: 60
Allocation: Randomized
Ages: 18 Years to 55 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Healthy Subjects

Keywords

Donepezil, Transdermal Delivery System

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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.

Study design

Phase: Phase 1
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 60 participants (actual)

Study arms

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
Experimental
Treatment B
10 mg/day Donepezil TDS 1-week wear and applied weekly for 5 consecutive weeks
Combination Product: Donepezil TDS
Active comparator
Treatment C
10 mg/day Aricept® donepezil tablet administered QD for 5 consecutive weeks
Drug: Aricept

Interventions

Combination productDonepezil TDS
Transdermal Delivery System
DrugAricept
Oral

What researchers measure

Primary outcomes

Maximum Concentration (Cmax)
To evaluate steady-state donepezil plasma exposure (Cmax) following 5 weeks of treatment.
Time frame: 35 days of each Treatment
Area Under the Curve (AUC)
To evaluate steady-state donepezil plasma exposure (AUC) following 5 weeks of treatment
Time frame: 35 days each Treatment

Results

Posted Sep 19, 2024

Participant flow

Treatment A - 5 mg TDS

Participant flow — Treatment A - 5 mg TDS
Milestone	Treatment Sequence ABC or ACB in Crossover Fashion
Started	60
Completed	57
Not completed	3
Withdrew: Physician decision	2
Withdrew: Failure to follow site rules	1

Treatment B - 10 mg TDS

Participant flow — Treatment B - 10 mg TDS
Milestone	Treatment Sequence ABC or ACB in Crossover Fashion
Started	55
Completed	53
Not completed	2
Withdrew: Protocol violation	1
Withdrew: Withdrawal by subject	1

Treatment C - 10 mg Oral

Participant flow — Treatment C - 10 mg Oral
Milestone	Treatment Sequence ABC or ACB in Crossover Fashion
Started	56
Completed	53
Not completed	3
Withdrew: Protocol violation	2
Withdrew: Failure to follow site rules	1

Outcome measures

PrimaryMaximum Concentration (Cmax)

To evaluate steady-state donepezil plasma exposure (Cmax) following 5 weeks of treatment.

Time frame:: 35 days of each Treatment
Reported as:: Mean · Cmax ng/ml

Maximum Concentration (Cmax)
Cmax ng/ml	Treatment A 5 mg TDS	Treatment B 10 mg TDS	Treatment C 10 mg Oral
Maximum Concentration (Cmax)	29.9 ± 9.1	62.4 ± 19.9	70.5 ± 19.4

PrimaryArea Under the Curve (AUC)

To evaluate steady-state donepezil plasma exposure (AUC) following 5 weeks of treatment

Time frame:: 35 days each Treatment
Reported as:: Mean · AUC h*ng/mL

Area Under the Curve (AUC)
AUC h*ng/mL	Treatment A 5 mg TDS	Treatment B 10 mg TDS	Treatment C 10 mg Oral
Area Under the Curve (AUC)	4366.0 ± 1380.1	9099.0 ± 2972.1	8462.6 ± 2558.0

Adverse events

Collected over Collected from first dose of the study drug to last treatment day, 36 days per intervention for a total of 108 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Treatment A - 5 mg TDS	0/60 (0%)	0/60 (0%)	32/60 (53.3%)
Treatment B - 10 mg TDS	0/55 (0%)	0/55 (0%)	30/55 (54.5%)
Treatment C - 10 mg Oral	0/56 (0%)	0/56 (0%)	32/56 (57.1%)

Most frequent other events

Showing 10 of 15

Most frequent other events
Event	Treatment A - 5 mg TDS	Treatment B - 10 mg TDS	Treatment C - 10 mg Oral
NauseaGastrointestinal disorders	4/60	1/55	17/56
Application Site PruritisGeneral disorders	12/60	5/55	0/56
DizzinessNervous system disorders	3/60	2/55	11/56
ConstipationGastrointestinal disorders	9/60	3/55	10/56
HeadacheNervous system disorders	8/60	8/55	7/56
DiarrhoeaGastrointestinal disorders	2/60	2/55	7/56
SomnolenceNervous system disorders	0/60	0/55	6/56
Muscle spasmsMusculoskeletal and connective tissue disorders	4/60	5/55	5/56
FatigueGeneral disorders	2/60	1/55	5/56
Application Site DermatitisGeneral disorders	5/60	3/55	1/56

Baseline characteristics

Age, Continuous
Age, Continuous(years)	All Study Participants
Mean	39.8 ± 9.91

Sex: Female, Male
Sex: Female, Male(Participants)	All Study Participants
Female	22
Male	38

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	All Study Participants
Race — Black of African American	3
Race — Asian	1
Race — White	56

Region of Enrollment
Region of Enrollment(participants)	All Study Participants
United States	60

Study locations

1 site

Worldwide Clinical Trials
San Antonio, Texas 78217, United States

References and documents

Study documents

Study protocol · Oct 26, 2020
Statistical analysis plan · Jul 15, 2021

Documents are hosted by the registry — open the source record to download them.

Registry details

Key details

Study ID: NCT04617782
Lead sponsor: Corium, Inc.
Responsible party: Sponsor
First posted: Nov 5, 2020
Start date: Dec 8, 2020
Primary completion: Apr 5, 2021
Completion: Apr 5, 2021
Results posted: Sep 19, 2024
Last update: Sep 19, 2024

Study contacts

Robert Bass, MD

principal investigator · Worldwide Clinical Trials

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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