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A Phase 1, Corplex™ Donepezil Transdermal System Compared to Oral Aricept®

Primary Purpose

Alzheimer Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Donepezil TDS Version A

Donepezil TDS Version B

Aricept

Donepezil TDS Version D

Donepezil TDS Version E

About this trial

This is an interventional treatment trial for Alzheimer Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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:

Sites / Locations

Celerion

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Donepezil TDS Version A

Donepezil TDS Version B

10 mg Aricept

Donepezil TDS Version D

Donepezil TDS Version E

Arm Description

Lead-in of 5 mg/day donepezil of target dose (1 x Corplex 5 mg donepezil transdermal delivery system; 7 days) followed by; Target dose of 10 mg/day donepezil (Treatment A); Corplex 10 mg donepezil transdermal delivery system. 1x patch will be worn for 7 days. A total of 4 TDS patches will be applied for 4 consecutive 7 day periods.

Lead-in of 5 mg/day donepezil of target dose (1 x Corplex 5 mg donepezil transdermal delivery system; 7 days) followed by; Target dose of 10 mg/day donepezil (Treatment B); Corplex 10 mg donepezil delivery transdermal system. 1x patch will be worn for 7 days. A total of 4 TDS patches will be applied for 4 consecutive 7 day periods.

5 mg/day oral Aricept, once daily for 7 days followed by; 10 mg/day Aricept once daily for 28 days

Target dose of 5 mg/day donepezil (Treatment D) Corplex 5 mg Donepezil TDS applied for a duration of 1 week.

Target dose of 5 mg/day donepezil (Treatment E) Corplex 5 mg Donepezil TDS applied for a duration of 1 week

Outcomes

Primary Outcome Measures

Steady-state PK

To evaluate the steady-state PK of donepezil following once weekly Corplex Donepezil TDS application compared to once-daily (QD) oral administration of Aricept. Aricept PK sampling time points; Day 1 (hr0,1,2,3,4,6,8,12); Day 2,8,15,22,29 (hr0); Day 35(hr0,1,2,3,4,6,8,12); Day 36-37,40,43,46,49,53 (hr0)

PK (Part B)

To compare the PK of 2 once-weekly Corplex Donepezil TDS treatments (target dose 5 mg donepezil/day)

Secondary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (Part A and B)

General Safety (AE and SAE as reported by subject following guidance CTCAE v4.0)

PI assessment of local skin irritation response to TDS (Part A and B)

To evaluate the safety and tolerability (including local skin irritation) of once-weekly Corplex Donepezil TDS. Skin irritation assessed using 8 pt categorical scale based on former FDA.gov/ohrms/dockets/98fr/990236GD.pdf. The Skin Irritation scale is: no irritation; minimal erythema/barely perceptible; definite erythema readily visible, minimal edema or minimal papular response; erythema and papules; definite edema; erythema, edema and papules; vesicular eruption; strong reaction spreading beyond application site.

PI assessment of TDS Adhesion per FDA UCM504157

To evaluate the adhesion of once-weekly Corplex Donepezil TDS. Adhesion is based on the adhered area (%) of the patch according to FDA.gov/downloads/Drugs/GuidanceComplianceRegulatory Information/Guidances/UCM504157.pdf. Specifically: ≥ 90% adhered (essentially no lift off skin); ≥ 75% to <90% adhered (some edges only lifting off skin); ≥ 50% to <75% adhered (less than half the TDS lifting off skin); < 50% adhered but did not detach (not detached, but more than half of the TDS lifting off skin without falling off); patch completely detached (TDS detached, completely off skin).

Full Information

NCT ID

NCT02968719

First Posted

November 13, 2016

Last Updated

July 31, 2018

Sponsor

Corium, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02968719

Brief Title

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

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

November 2016 (Actual)

Primary Completion Date

July 11, 2017 (Actual)

Study Completion Date

July 11, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Corium, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Masking Description

Open Label

Allocation

Randomized

Enrollment

107 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Donepezil TDS Version A

Arm Type

Experimental

Arm Description

Arm Title

Donepezil TDS Version B

Arm Type

Experimental

Arm Description

Arm Title

10 mg Aricept

Arm Type

Active Comparator

Arm Description

5 mg/day oral Aricept, once daily for 7 days followed by; 10 mg/day Aricept once daily for 28 days

Arm Title

Donepezil TDS Version D

Arm Type

Experimental

Arm Description

Target dose of 5 mg/day donepezil (Treatment D) Corplex 5 mg Donepezil TDS applied for a duration of 1 week.

Arm Title

Donepezil TDS Version E

Arm Type

Experimental

Arm Description

Target dose of 5 mg/day donepezil (Treatment E) Corplex 5 mg Donepezil TDS applied for a duration of 1 week

Intervention Type

Drug

Intervention Name(s)

Donepezil TDS Version A

Intervention Description

Donepezil Hydrochloride Transdermal Delivery System (5mg and 10 mg Version B)

Intervention Type

Drug

Intervention Name(s)

Donepezil TDS Version B

Intervention Description

Donepezil Hydrochloride Transdermal Delivery System (5 mg and 10 mg Version B)

Intervention Type

Drug

Intervention Name(s)

Aricept

Other Intervention Name(s)

Aricept Tablet

Intervention Description

Aricept (5 mg and 10 mg) Donepezil Hydrochloride

Intervention Type

Drug

Intervention Name(s)

Donepezil TDS Version D

Intervention Description

Donepezil Hydrochloride Transdermal Delivery System (5 mg Version D)

Intervention Type

Drug

Intervention Name(s)

Donepezil TDS Version E

Intervention Description

Donepezil Hydrochloride Transdermal Delivery System (5 mg Version E)

Primary Outcome Measure Information:

Title

Steady-state PK

Description

Time Frame

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);

Title

PK (Part B)

Description

To compare the PK of 2 once-weekly Corplex Donepezil TDS treatments (target dose 5 mg donepezil/day)

Time Frame

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 Outcome Measure Information:

Title

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (Part A and B)

Description

General Safety (AE and SAE as reported by subject following guidance CTCAE v4.0)

Time Frame

Daily during 36-day confinement period and 7 visits over the 21 day wash-out period.

Title

PI assessment of local skin irritation response to TDS (Part A and B)

Description

Time Frame

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.

Title

PI assessment of TDS Adhesion per FDA UCM504157

Description

Time Frame

Twice daily during 36-day confinement period

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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:

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Danielle Armas, MD

Organizational Affiliation

Celerion

Official's Role

Principal Investigator

Facility Information:

Facility Name

Celerion

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85283

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

No Plans

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A Phase 1, Corplex™ Donepezil Transdermal System Compared to Oral Aricept®

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