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Trial registered on ANZCTR


Registration number
ACTRN12620000199910
Ethics application status
Approved
Date submitted
19/12/2019
Date registered
20/02/2020
Date last updated
26/02/2020
Date data sharing statement initially provided
20/02/2020
Date results information initially provided
26/02/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1, Healthy Volunteer Study to Assess a Patch Delivery System for Alzheimer's type Dementia
Scientific title
A Phase 1, Randomized, Blinded, 2-Way Crossover Study to in Healthy Volunteers to Assess the Relative Bioavailability of Corplex (TM) Donepezil Transdermal Delivery Systems With and Without Crystals
Secondary ID [1] 299575 0
CL-P-19005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's type dementia 314850 0
Condition category
Condition code
Neurological 313190 313190 0 0
Alzheimer's disease
Neurological 314115 314115 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomized, blinded, 2-way crossover study of a once-weekly 10mg/day Corplex® Donepezil Transdermal Delivery Systems (TDS). This study will evaluate if there are any differences in absorption of Donepezil in a TDS containing crystals (covering >0.1 and <1%) and TDS with no crystals.

All eligible participants will be randomized to 1 of 4 treatment sequences as described below:

Period 1 Period 2
Treatment Sequence 1 TDS A: Left Back TDS B: Right Back
Treatment Sequence 2 TDS B: Left Back TDS A: Right Back
Treatment Sequence 3 TDS A: Right Back TDS B: Left Back
Treatment Sequence 4 TDS B: Right Back TDS A: Left Back
TDA A= with crystals; TDS B=without crystals

Each participant will participate in 2 periods. In the first period, the participant will receive a single TDS (A or B) placed on the mid-lower back by clinical staff (such as nurses). The TDS will be worn for 7 days. After a washout period of 49 days, the participant will have the other TDS type applied to the opposite mid-lower back for 7 days (1 week) during Treatment Period 2 and will then be followed for 28 days after TDS removal.

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] 315838 0
Treatment: Drugs
Comparator / control treatment
Corplex Donepezil TDS is a transdermal patch intended for a 7 day application. Each TDS contains 1.85 mg donepezil HCl/cm2. Each participant will have a single 105 cm2 TDS of 10 mg donepezil/day comparing systems with crystals between >0.1% and <1% and without crystals.
Control group
Active

Outcomes
Primary outcome [1] 321708 0
The primary objective of this study is to assess relative bioavailability of donepezil from a single application of once-weekly Corplex™ Donepezil Transdermal Delivery Systems (TDS) with crystals compared to Corplex Donepezil TDS without crystals.
Timepoint [1] 321708 0
Blood samples for donepezil PK will be collected at the following time points: Prior to TDS application (0 hour) and at 2, 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 170, 174, 180, 192, 216, 240, 288, 312, 360, 432, 504, 600, 672, 696, and 840 hours following Corplex Donepezil TDS application. The patch is removed at 168 hours post application.
Secondary outcome [1] 375980 0
The secondary objective of this study is to evaluate the safety and tolerability (including local skin irritation) of Corplex Donepezil TDS.
Timepoint [1] 375980 0
Skin irritation assessments will be performed prior to TDS application and at 0.5, 24, 48, and 72 hours following TDS removal.

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

Physical exams: Screening, Day -1, and Day 36 of each treatment.

12-Lead Electrocardiogram: Screening, Day -1, Day 1, Day 8, and Day 36 of each treatment period.

Vitals: All visit days

Safety blood sampling: Screening, Day -1, Day 8, and Day 36 of each treatment period.

Suicidal ideation assessments: Screening and Day 8 of each treatment period.

Adverse event and concomitant medications will be reviewed at all visits from the time the subject signs consent to End of Study

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) and 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 methods 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 level, or have official documentation of at least 1 of the sterilization procedure no less than 6 months prior to Screening.

7. For a male: must agree to an acceptable birth control methods from Screening until after the End of Study Visit
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. Has intolerance to venipuncture and/or inability to comply with the extensive blood sampling required for this study or does not have suitably intact veins in both arms.

6. Potential for occupational exposure to anticholinesterase agents in the 5 weeks prior to Screening through the last TDS removal.

7. Female subjects with a positive pregnancy test or who are lactating

8. 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.

9. 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.

10. 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

11. History of or current consumption of high levels of caffeine (equivalent to 3 regular cups of coffee or 2 energy drinks, per day).

12. 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 by randomization number with no information of the crystal content. Site staff will remain blinded during the study and only the pharmacists 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 pharmacy will consecutively assign 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. Participants will be randomized to 1 of 4 treatment sequences. The 4 treatment sequences represent two 2x2 crossover study designs, 1 for each side of the back sequence that receives each of the Corplex Donepezil TDS types during the 2 study periods (i.e., left side Period 1 followed by right side Period 2 or right side Period 1 followed by left side Period 2)
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)
Bio-availability
Statistical methods / analysis
Approximately 48 healthy subjects, with an equal number of subjects randomized to the treatment sequences, will be enrolled in the study to enable 42 subjects to complete both study periods. This sample size allows for up to 6 dropouts and still provide at least 90% power to assess bioequivalence of Cmax within the limits of 80 to 125% for the geometric mean ratio of the Corplex Donepezil TDS with crystals compared to the Corplex Donepezil TDS without crystals if the true expected geometric mean ratio is 0.97.

Recruitment
Recruitment status
Active, not 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] 15001 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 28286 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 304059 0
Commercial sector/Industry
Name [1] 304059 0
Corium Inc.
Address [1] 304059 0
235 Constitution Drive
Menlo Park, California, 94025, USA
Country [1] 304059 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Corium Inc.
Address
235 Constitution Drive
Menlo Park, California, 94025, USA
Country
United States of America
Secondary sponsor category [1] 304252 0
Commercial sector/Industry
Name [1] 304252 0
InClin PTY lTD
Address [1] 304252 0
210 / 25 Berry Street
North Sydney, NSW
Australia, 2060
Country [1] 304252 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304550 0
Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 304550 0
Old Baker Building
Level 1
55 Commercial Rd
Melbourne, VIC 3004
Ethics committee country [1] 304550 0
Australia
Date submitted for ethics approval [1] 304550 0
30/10/2019
Approval date [1] 304550 0
25/11/2019
Ethics approval number [1] 304550 0

Summary
Brief summary
This is a single-site, phase 1, randomized bioavailability study to assess a patch delivery system with and without crystals to be used in Alzheimer's type dementia. The study will enroll 48 healthy volunteers with approximately equal distribution of male and female volunteers. The total study duration is 133 days and includes a 42-day screening window and 2 treatment periods of 36 days each. There will be a washout period between Period 1 and Period 2.

In the first treatment period, each participant will receive a single application of once weekly Corplex Donepezil TDS (with or without crystals), applied to either the left or right side of the back according to his or her randomization. After the washout period, the participant will have the other Corplex Donepezil TDS type applied on the opposite side of the back during Treatment Period 2.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97350 0
Dr Ingrid Hopper
Address 97350 0
The Nucleus Network
Burnet Tower AMREP Precinct
89 Commercial Road
Melbourne, VIC 3001
Country 97350 0
Australia
Phone 97350 0
+61 3 9076 8960
Fax 97350 0
Email 97350 0
i.hopper@nucleusnetwork.com.au
Contact person for public queries
Name 97351 0
Mr Taylor Kilfoil
Address 97351 0
InClin PTY LTD
210/25 Berry Street
North Sydney, NSW
Australia, 2060
Country 97351 0
Australia
Phone 97351 0
+61 408 880 403
Fax 97351 0
Email 97351 0
taylorkilfoil@inclin.com
Contact person for scientific queries
Name 97352 0
Ms Vaeling Miller
Address 97352 0
Corium Inc.
235 Constitution Drive
Menlo Park, California 94025, USA
Country 97352 0
United States of America
Phone 97352 0
+1 650 353 7201
Fax 97352 0
Email 97352 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
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary