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Trial registered on ANZCTR


Registration number
ACTRN12620000204943p
Ethics application status
Submitted, not yet approved
Date submitted
28/01/2020
Date registered
20/02/2020
Date last updated
22/04/2020
Date data sharing statement initially provided
20/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Healthy Volunteer Study to Evaluate the Effect of Differing Bonding Strengths on the Adhesion of a Patch Delivery System for Alzheimer's type Dementia
Scientific title
A Phase 1, Randomized, 4-Way Crossover Study to Evaluate the Effect of Varying Bonding Strength Between Active and Inactive Layers on Adhesion of the Corplex™ Donepezil Transdermal Delivery System in Healthy Volunteers
Secondary ID [1] 300352 0
CL-P-20001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's type dementia 315976 0
Condition category
Condition code
Neurological 314254 314254 0 0
Alzheimer's disease
Neurological 314255 314255 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomized, 4-way crossover study to evaluate the effects of 4 different bonding strengths on the wear performance of a once-weekly 10mg/day Corplex Donepezil Transdermal Delivery (TDS).

The 4 different bonding strengths are:
1. Control (TDS B) - The current strength that is used in previous clinical studies and will serve as the control strength (TDS B) in this study
2. Low (TDS C) - Approximately 12% greater in bonding strength than the control
3. Medium (TDS D) - Approximately 25% greater in bonding strength than the control
4. High (TDS E) - Approximately 37% greater in bonding strength than the control

Eligible participants will receive all 4 types of TDS (B, C, D, and E) in a randomized order in 4 consecutive treatment periods. In each treatment period, the participant will wear a single TDS placed on the back by clinic staff (including nurses) and worn for 7 days. On the day the TDS patch is removed, another TDS patch of different strength will be placed.

Safety laboratory tests, physical examinations, vital signs, ECGs, adhesion assessments, and skin irritation assessments will be performed to monitor safety and compliance.
Intervention code [1] 316643 0
Treatment: Drugs
Comparator / control treatment
Corplex Donepezil TDS is a transdermal patch intended for a 7-day application. Each TDS is 105 cm2 in size containing 185 mg donepezil HCl/cm2. and is designed to deliver 10 mg of donepezil per day.

Three different types of TDS will be evaluated in this study against one control:

TDS Treatment B - Control (current TDS)
TDS Treatment C - Applied Bonding Strength (Low)
TDS Treatment D - Applied Bonding Strength (Medium)
TDS Treatment E - Applied Bonding Strength (High)

Control group
Active

Outcomes
Primary outcome [1] 322637 0
To assess the wear/adhesion performance of 4 Corplex Donepezil TDS varying in bond strength.
Timepoint [1] 322637 0
Patch adhesion will be evaluated every 12 hours during each patch wear. Adhesion will be rated on a 12-point assessment scale ranging from 0 (patch remains 100%) adhered) to 11 ( patch is detached).

Secondary outcome [1] 379140 0
To evaluate the safety and tolerability (including local skin irritation) of 4 Corplex Donepezil TDS varying in bond strength.
Timepoint [1] 379140 0
Skin irritation assessments will be performed prior to each TDS application and at 0.5, 24, 48, and 72 hours following each TDS removal. Skin irritation will be assessed using 2 sets of scales - a Dermal Response Scale assessing irritation and edema and the Other Effects Scale assessing appearance.

Safety will be monitored throughout the study by repeated clinical and laboratory evaluations including:

Physical exams: Screening, Day -1, and Day 57.

12-Lead Electrocardiogram: Screening, Day -1, and Day 57.

Vital Signs (blood pressure, pulse, respiration, temperature): Screening, daily from Day -1, to Day 32, and Day 57.

Safety clinical lab tests consisting of chemistry, hematology, urinalysis, and coagulation: Screening, Day -1. Day 29, and Day 57.

Suicidal ideation assessments through the Columbia-Suicide Severity Scale: Screening and Day 30

Adverse events and concomitant medications will be reviewed at all visits from the time the participant signs consent to Day 57.

Eligibility
Key inclusion criteria
Key inclusion criteria include:
1. Healthy, adult, male or female, at least 18 years of age at Screening,
2. Nonsmoker or occasional smoker (less than or equal to 1 cigarette or equivalent/day) must agree not to smoke or agree to consume no more than 1 cigarette or equivalent/day from the Screening Visit until after the End of Study Visit.
3. Body mass index between 18.0 and 32.0 kg/m2 at Screening.
4. Sparse, minimal, and fine hair on skin at application sites
5. If a female of childbearing potential: must be either sexually inactive (abstinent) for at least 14 days prior to the first TDS application and remain sexually inactive throughout the study or be using an acceptable birth control method while within the study.
6. A female of nonchildbearing potential: defined as either postmenopausal with amenorrhea for at least 1 year prior to Screening AND have an acceptable follicle-stimulating hormone serum levels or have official documentation of at least 1 sterilization procedures no less than 6 months prior to Screening.
7. For a male: must agree to use an acceptable birth control method from Screening AND for at least 90 days following the last TDS removal
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Key exclusion criteria include:
1. History of any clinically significant medical or psychiatric condition or disease that, in the opinion of the investigator, might confound the results of the study or poses an additional risk to the subject by participation in the study
2. History of alcoholism or drug abuse within the past 2 years prior to the first study product treatment, or current alcohol or drug abuse
3. History of significant multiple, severe contact allergies, or has had 1 or more anaphylactic reactions, or is significantly intolerant to prescription or nonprescription drugs.
4. Exhibiting symptoms suggestive of bladder outflow obstruction as assessed by the investigator.
5. Potential for occupational exposure to anticholinesterase agents in the 5 weeks prior to Screening through the last TDS removal.
6. Female subjects with a positive pregnancy test or who are lactating.
7. History or presence of hairy skin on application sites that may potentially interfere with TDS adhesion and drug absorption. Clipping is permitted to remove fine or sparse hair. Subjects with heavy hair growth at the application site will not be eligible even with clipping.
8. History or presence of significant skin damage, diffuse skin diseases, scars, tattoos on the application sites, or other skin disturbances or coloration that would interfere with placement of test articles, skin assessment, or reactions to drug as deemed by the investigator to potentially interfere with drug absorption or irritation assessments; subjects with a spray tan applied less than 30 days prior to study dose are excluded.
9. History or presence of significant dermatological disease or condition, such as atopy, psoriasis, vitiligo or conditions that are known to alter the skin appearance or physiologic response.
10. History of or current consumption of high levels of caffeine (equivalent to 3 regular cups of coffee or 2 energy drinks, per day).
11. Donation of blood or significant blood loss within 56 days prior to the first study product treatment.
13. Plasma donation within 7 days prior to the first study product treatment.
14. Use of donepezil HCl or related drugs within 60 days prior to the first study product treatment.
15. Clinically significant depression symptoms or suicidal ideation or behavior.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patches will be packaged and labeled with no information on bond strength. Site staff will remain blinded during the study and only the pharmacist will be unblinded.

Code break envelopes for emergency unblinding will be provided to the clinical site.

Participants will receive a 3-digit screening number at the Screening Visit, following informed consent. The site pharmacist will consecutively assess participants to a randomization number according to the randomization schedule as they become eligible for the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization sequence will be produced by an unblinded programmer/statistician using a computerized sequence generation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Thirty-six participants, with an equal number of participants randomized to the treatment sequences, will be enrolled in the study to enable 30 participants to complete all 4 study periods. This sample size allows for up to 6 dropouts and still provides at least 90% power to demonstrate non-inferiority between one of the electrostatic charged treatments (TDS C, TDS D or TDS E) and the control treatment (TDS B). The sample size calculation is based on simulations comparing 2 paired distributions using one-sided t-tests, assuming a correlation of 0.25 between paired items and a standard deviation of 0.6.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 15687 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 29106 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 304775 0
Commercial sector/Industry
Name [1] 304775 0
Corium Inc.
Address [1] 304775 0
235 Constitution Drive
Menlo Park, California, 94025
Country [1] 304775 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Corium Inc.
Address
235 Constitution Drive
Menlo Park, California, 94025
Country
United States of America
Secondary sponsor category [1] 305091 0
Commercial sector/Industry
Name [1] 305091 0
InClin Pty Ltd
Address [1] 305091 0
25 Berry Street, Suite 210
North Sydney, NSW, 2060
Country [1] 305091 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305190 0
Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 305190 0
Old Baker Building
Level 1
55 Commercial Rd
Melbourne, VIC 3004
Ethics committee country [1] 305190 0
Australia
Date submitted for ethics approval [1] 305190 0
20/01/2020
Approval date [1] 305190 0
Ethics approval number [1] 305190 0

Summary
Brief summary
This is a single-site phase 1, randomized, crossover study to assess the effects of 4 different bond strengths on the performance of a patch delivery system to be used in Alzheimer's type dementia. The study will enroll 36 participants. The total study duration is 98 days which includes a 42-day screening window, 4 consecutive treatment periods, and 3 follow-up visits over 28 days.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99550 0
Dr Ingrid Hopper
Address 99550 0
The Nucleus Network
Burnet Tower AMREP Precinct
89 Commercial Road
Melbourne, VIC 3001
Country 99550 0
Australia
Phone 99550 0
+61 3 9076 8960
Fax 99550 0
Email 99550 0
i.hopper@nucleusnetwork.com.au
Contact person for public queries
Name 99551 0
Mr Taylor Kilfoil
Address 99551 0
InClin Pty Ltd
25 Berry Street, Suite 210
North Sydney, NSW 2060
Country 99551 0
Australia
Phone 99551 0
+61 408 880 403
Fax 99551 0
Email 99551 0
taylorkilfoil@inclin.com
Contact person for scientific queries
Name 99552 0
Ms Vaeling Miller
Address 99552 0
Corium Inc.
235 Constitution Drive
Menlo Park, California, 94025
Country 99552 0
United States of America
Phone 99552 0
+1 650 353 7201
Fax 99552 0
Email 99552 0
vmiller@coriumintl.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data to remain confidential
What supporting documents are/will be available?
No other documents available
Summary results
No Results