Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000574145p
Ethics application status
Submitted, not yet approved
Date submitted
6/02/2019
Date registered
11/04/2019
Date last updated
11/04/2019
Date data sharing statement initially provided
11/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate the safety and tolerability of multiple formulations of an investigational transdermal patch in healthy volunteers
Scientific title
An Exploratory Clinical Study to Evaluate the Skin Tolerability, Drug Delivery and Safety of Multiple Formulations of Once-Weekly Investigational Transdermal Delivery System in Healthy Volunteers
Secondary ID [1] 297287 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 311365 0
Condition category
Condition code
Neurological 310003 310003 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1: Two Transdermal Patch one with each Mem4 (2.9 mg memantine/day), Mem5 (3.7 mg memantine/day)applied concurrently to either arm as randomized (left or right) for a continuous period of 7 days.
Group 2: One Transdermal Patch (Mem4 or Mem5, defined by results from Group 1) will be applied over a film of corticosteroid of 0.1% or 0.5% concentration, concurrently to either arm as randomized (left or right) for a continuous period of 7 days.

Group 1 safety and tolerability data will be primary determining factor to define the patch used in Group 2.
Intervention code [1] 313537 0
Treatment: Drugs
Comparator / control treatment
Active Control Mem4 (2.9 mg memantine/day) and Mem5 (3.7 mg memantine/day) will be compared for skin tolerability.

Both treatment are active drugs and will be evaluated against each other to determine the dose for Group 2. There is no reference product used in this study
Control group
Dose comparison

Outcomes
Primary outcome [1] 318913 0
Assess the skin tolerability of two TDS formulations of memantine patch. Skin tolerability will be assessed through the use of scales; [8-point categorical dermal response scale (0-7), Other effects categorical scale (0-5)] as well as by Adhesion parameters (12 percentage point increments).

This is a composite outcome and will be evaluated for Group 1 and Group 2 part.
Timepoint [1] 318913 0
Skin tolerability for each TDS formulations will be assessed and scored post-patch removal at every 24 hours for at least 72-hours until the score returns to zero. Adhesion Parameters: assessed every 24 hours +/-1 hours from the time of patch application until removal.

Skin Tolerability will be assessed on Day 1 to 8 and assessed every 24 hours until 72-hours post-patch removal. Post removal assessments include the following time point window: +/- 6 hours at 48 (Day 10) and 72 hours (Day 11); +/- 1 day at Days 13, 15, and 17

This will be evaluated for both Group 1 and Group 2. Group 2 will assess a single patch (determined from Group 1) following administration of two concentration of corticosteroid.

This outcome will be evaluated for both Group 1 and Group 2. Group 2 will assess skin tolerability only for one single TDS formulation which will be determined from Group 1 outcome.
Secondary outcome [1] 366406 0
The drug delivery of the TDS formulation (Mem4 or Mem5, confirmed from group 1 results) applied to group 2 subjects will be evaluated by collection of blood samples. Drug delivery will be assessed by drug concentration present in blood.
Timepoint [1] 366406 0
Blood samples will be collected at pre-dose and 96, 120, 144, 168 hours (+/-1 hours) following application for group 2 subjects.
Secondary outcome [2] 366407 0
Skin tolerability of TDS formulation (Mem4 or Mem5, confirmed from group 1 results) with combination of topical corticosteroid will be assessed. This outcome will be assessed for Group 2 and will be assessed and scored as soon as possible but no later than 30 minutes post-patch removal for at least 72 hours and prior to application of patch using an 8-point categorical scale and a 6-point categorical scale
Timepoint [2] 366407 0
Skin tolerability of TDS formulation will be assessed and scored as soon as possible post-patch removal for at least 72 hours and prior to application of patch. Post removal assessments include the following time point windows: +/- 6 hours at 48 (Day 10) and 72 hours (Day 11); +/- 1 day at Days 13, 15, and 17.
Secondary outcome [3] 366408 0
Determine safety by assessing AE’s, use of concomitant medications, physical examination (respiratory, cardiovascular, and gastrointestinal systems, weight, and BMI), vital signs (blood pressure, heart rate, respiratory rate, and body temperature), clinical lab sampling (hematology and chemistry) and urine (urinalysis) and 12-lead ECGs. This outcome will be assessed for both Group 1 and Group 2

Possible most frequent and common AEs are: pruritus, application site pain, dizziness and headaches.
Timepoint [3] 366408 0
Adverse Events will be recorded from time of informed consent until Day 29 post dose.
Secondary outcome [4] 367532 0
Adhesion Parameters: assessed every 24 hours +/-1 hours from the time of patch application until removal.
Timepoint [4] 367532 0
Adhesion Parameters: assessed every 24 hours +/-1 hours from the time of patch application until removal.

Eligibility
Key inclusion criteria
1. Healthy, adult, Caucasian females and males aged 50 to 85 years (inclusive) on the day of randomization. Enrollment will aim for 100 percent females; however, up to 25 percent males may be enrolled per the Sponsor’s approval and a minimum of 5 subjects (3-4 females, and 1-2 males if applicable) who are between the ages of 70 and 85 years.
2. Has a body mass index (BMI) between 18-32 kg/m^2 (inclusive).
3. Have a Fitzpatrick skin type of I, II, or III
4. Must be willing and able to understand and comply with the scheduled study visits, treatment plans, laboratory tests, and other procedures by providing a signed and dated written informed consent prior to the initiation of any study procedures.
5. Women of child-bearing potential and men should be sexually inactive (abstinent). Abstinence, defined as complete avoidance of heterosexual intercourse, is an acceptable form of contraception. .
6. Willing and able to discontinue all nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) NSAID analgesic therapy, 30 days prior to Day 1 and until completion of the Study Exit Visit.
7. If the subject is receiving allowed medications for the treatment of non-excluded medical conditions, the dose must be stable for at least 28 days before randomization on Day 1.
Minimum age
50 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Participation in another clinical study with an IP or device within 30 days or 5 half-lives, whichever is longer, prior to screening.
2. Plasma donation within 28 days of screening or any blood donation or blood loss greater than 500 mL within 3 months of screening.
3. Has skin color that may not allow reliable evaluation of irritation.
4. Female subjects with a positive pregnancy test or lactating.
5. Has intolerance to venipuncture and/or inability to comply with the blood sampling required for this study.
6. Has cuts, scratches/abrasions, scars, breaks in the skin surface, skin with excessive hair, indications of sunburn, excessive skin tanning, stretch marks at the application site, recent tattoos (within the last 6 months) or has any abnormalities at the intended application sites which would affect absorption of the IP.
7. Unwilling to refrain from using tanning salons, saunas, or from sunbathing during the course of the study. Unwilling to avoid shaving of the application site, waxing of the application site, or using lotion hair remover on or near application site from 48 hours before patch application and during the conduct of the study.
8. Has a history of or is currently consuming high caffeine levels
9. Smokes more than 20 cigarettes per day for more than 10 years
10. Presence of any major psychiatric disorder
11. Significant cardiovascular disease
12. Significant or chronic lung disease
13. Diabetes complicated
14. Known or suspected systemic infection
15. History of severe allergy/hypersensitivity reactions
16. History of cancer
17. Transient ischemic attack or stroke in the last 3 years.
18. History of suspected alcohol or drug dependence
19. Myocardial infarction, hospitalization for unstable angina or arrhythmia or unexplained syncope
20. Clinically important infection, including chronic, persistent or acute infection, within 3 months of screening or between screening and randomization.
21. Any medical or surgical procedure or trauma within 28 days of Day 1.
22. Current serious or unstable clinically important illness,
23. Exhibiting symptoms suggestive of bladder outflow obstruction
24. Has a history of allergic reactions to medical grade adhesive tapes, sunscreens, cosmetics, lotions, fragrances, or latex.
25. Use of adjuvant analgesics
26. Use of muscle relaxants
27. Use of any topical medication in the areas intended for patch application within 14 days prior to the first patch application and throughout the study.
28. Use of any topical products without medicinal ingredient (including but not limited to perfumes, body lotions, sunscreens, spray or patch oils, creams and alcohol) on the area intended for patch application within 48 hours prior to the first patch application
29. Prior or current use of memantine hydrochloride, or to piperidine derivatives and related drugs.
30. Clinically important abnormality in physical examination, vital signs or clinical laboratory test.
31. Clinically significant hypertension
32. Any clinically significant abnormality in ECG rhythm, conduction or morphology
33. A positive pregnancy test at screening

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)
Participants will be assigned a randomization number from a randomization list, maintained by site pharmacist which will be allocated to a treatment group based on a randomization schedule. Allocation is randomized only to ensure eligible subjects are randomized to 3 possible Group 1 or 3 possible Group 2 treatment .
Allocation involved contacting the holder ( off-site pharmacist) of the allocation schedule who will then assign the treatment
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Each subject will be assigned with a unique identification number based on the randomization table created by computer software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Analyses will be of a descriptive nature. Descriptive statistics will consist of summary statistics (number of non-missing observations, mean, standard deviation, minimum, median, and maximum) for continuous data and frequency counts and percentages for categorical data.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2019
Actual
Date of last participant enrolment
Anticipated
30/08/2019
Actual
Date of last data collection
Anticipated
30/09/2019
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 13029 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 25523 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 301846 0
Commercial sector/Industry
Name [1] 301846 0
Corium International, Inc.
Country [1] 301846 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
INC Research Australia Pty Ltd
Address
159 Port Road
Hindmarsh, SA 5007
Adelaide, Australia
Country
Australia
Secondary sponsor category [1] 301591 0
None
Name [1] 301591 0
None
Address [1] 301591 0
None
Country [1] 301591 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 302546 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 302546 0
Ethics committee country [1] 302546 0
Australia
Date submitted for ethics approval [1] 302546 0
06/02/2019
Approval date [1] 302546 0
Ethics approval number [1] 302546 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90598 0
Dr James Kuo
Address 90598 0
Scientia Clinical Research Ltd, Bright Building Level 5, Corner High and Avoca Streets, Randwick, NSW 2031
Country 90598 0
Australia
Phone 90598 0
+61 293825800
Fax 90598 0
Email 90598 0
[email protected]
Contact person for public queries
Name 90599 0
Lisa Nelson
Address 90599 0
Scientia Clinical Research Ltd, Bright Building Level 5, Corner High and Avoca Streets, Randwick, NSW 2031
Country 90599 0
Australia
Phone 90599 0
+61 438 008 816
Fax 90599 0
Email 90599 0
[email protected]
Contact person for scientific queries
Name 90600 0
Vaeling Miller
Address 90600 0
Corium International, Inc
235 Constitution Drive
Menlo Park
CA
94024, USA
Country 90600 0
United States of America
Phone 90600 0
+1 408 203 1726
Fax 90600 0
Email 90600 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
As this is a Phase 1 study, only aggregate data may be posted/published.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.