Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001993280
Ethics application status
Approved
Date submitted
6/12/2018
Date registered
12/12/2018
Date last updated
12/12/2018
Date data sharing statement initially provided
12/12/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to evaluate the safety and tolerability of an investigational transdermal patch in healthy volunteers.
Scientific title
An Exploratory Clinical Study to Evaluate the safety and Skin Tolerability of Multiple Formulations of Once Weekly Investigational Transdermal Delivery System in Healthy Volunteers
Secondary ID [1] 296805 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 310693 0
Condition category
Condition code
Neurological 309394 309394 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Three Transdermal Patches [Mem1 (5.5 mg memantine/day), Mem2 (4.6 memantine/day) and Mem3 (Placebo)] will be applied to each participant concurrently to a randomized arm (left or right) for a continuous period of 7 days.
Composition of patches are: backing, adhesive/drug matrix (Mem1 and Mem2 contains memantine, at different concentrations, and no drug for Mem3 placebo patch), release liner.
Patches are 6 cm x 4.2 cm rectangular patch and will be applied to approximately 1 cm away from the center of the spine.
Clinical staff will review patch daily as per protocol and subject will be asked to report if they notice adhesion to clothing, bedding or anything unusual.
Details of patch allocation per subject included as Attachment 1.
Intervention code [1] 313095 0
Treatment: Drugs
Comparator / control treatment
Proprietary three layer transdermal patch system (backing, adhesive/drug matrix, release liner) matching description of active patch sans API (memantine)
Control group
Placebo

Outcomes
Primary outcome [1] 308349 0
Assess skin tolerability of three formulations of Memantine patch. Skin tolerability will be assessed through the use of two scales; Dermal Response Scale (8-point categorical scale (0-7)) and Other Effects Scale (6-point categorical scale (0-5)]. Both scales will be used to assess the single primary outcome of skin tolerability.
Timepoint [1] 308349 0
Skin irritation for each transdermal patch will be assessed and scored post-patch removal for at least 72-hours or until scores return to a zero..
Primary outcome [2] 308372 0
Assess skin adhesion of three formulations of Memantine patch. Skin adhesion will be assessed through the use of Adhesion parameters [12-point categorical scale (0-11)]
Timepoint [2] 308372 0
Adhesion Parameters: assessed every 24 hours +/-1 hours from the time of patch application until removal.
Secondary outcome [1] 354680 0
To determine the safety of the application of transdermal patches when applied to healthy participants. Safety will be assessed by looking at the incidence, severity, causality and seriousness of adverse events; use of concomitant medications; physical examinations(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); urine (urinalysis); and 12-lead ECGs.
Assessments will be made by the clinical staff under confinement at site by use of ECG, BP cuffs, weight scales, CS lab values and urinalysis.
This is a composite outcome, safety is assessed by each of the components.
Timepoint [1] 354680 0
Adverse Events will be recorded from time of participant's check in (day-1) until Day 29 post dose.

Eligibility
Key inclusion criteria
General
1. Healthy, adult, Caucasian females and males aged 30 to 65 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
2. Has a body mass index 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 non-steroidal 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
30 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
General
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, recent tattoos (within the last 6 months) at the application site, skin with excessive hair, indications of sunburn, excessive skin tanning, stretch marks and/or similar abnormalities at the intended application sites
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
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. Myocardial infarction, hospitalization for unstable angina or arrhythmia or unexplained syncope
19. Clinically important infection
20. Any medical or surgical procedure or trauma within 28 days
21. Current serious or unstable clinically important illness
22. Has a history of allergic reactions to medical grade adhesive tapes, sunscreens, cosmetics, lotions, fragrances, or latex.
23. Use of adjuvant analgesics
24. Use of muscle relaxants
25. Use of any topical medication in the areas intended for patch application
26. 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
27. Prior or current use of fingolimod hydrochloride, memantine hydrochloride, or to piperidine derivatives and related drugs.
28. Clinically important abnormality
29. Heart rate less than or equal to 60 bpm.
30. Clinically significant hypertension
31. Any clinically significant abnormality in electrocardiogram (ECG) rhythm
32. 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 equal opportunity for the 2 patches to be placed on the right or left side of the back and the single patch to be placed on the opposite side.
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)
Simple randomization using a randomization table created by computer software (i.e. computerized sequence generation)
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
Recruiting
Date of first participant enrolment
Anticipated
Actual
29/11/2018
Date of last participant enrolment
Anticipated
30/01/2019
Actual
Date of last data collection
Anticipated
27/02/2019
Actual
Sample size
Target
12
Accrual to date
14
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 12664 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 25083 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 301378 0
Commercial sector/Industry
Name [1] 301378 0
Corium International, Inc.
Country [1] 301378 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] 301046 0
None
Name [1] 301046 0
Address [1] 301046 0
Country [1] 301046 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302116 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 302116 0
129, Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 302116 0
Australia
Date submitted for ethics approval [1] 302116 0
19/09/2018
Approval date [1] 302116 0
26/11/2018
Ethics approval number [1] 302116 0
2018 08 623

Summary
Brief summary
This research project is being conducted to investigate the safety and tolerability of a single application of a transdermal drug delivery system containing memantine HCl when administered to healthy volunteers.
Trial website
None
Trial related presentations / publications
None
Public notes
None

Contacts
Principal investigator
Name 89166 0
Dr James Kuo
Address 89166 0
Scientia Clinical Research Ltd, Bright Building Level 5, Corner High and Avoca Streets, Randwick, NSW 2031
Country 89166 0
Australia
Phone 89166 0
+61 293825800
Fax 89166 0
Email 89166 0
james.kuo@scientiaclinicalresearch.com.au
Contact person for public queries
Name 89167 0
Ms Lisa Nelson
Address 89167 0
Scientia Clinical Research Ltd, Bright Building Level 5, Corner High and Avoca Streets, Randwick, NSW 2031
Country 89167 0
Australia
Phone 89167 0
+61 438 008 816
Fax 89167 0
Email 89167 0
lisa.nelson@scientiaclinicalresearch.com.au
Contact person for scientific queries
Name 89168 0
Ms Vaeling Miller
Address 89168 0
Corium International, Inc
235 Constitution Drive
Menlo Park
CA
94024, USA
Country 89168 0
United States of America
Phone 89168 0
+1 408 203 1726
Fax 89168 0
Email 89168 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
As this is a Phase 1 study, only aggregate data may be posted/published.
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
Other
'Other' documents specified
Selected summary information may be available from the CSR.
How or where can supporting documents be obtained?
Type [1] 667 0
Other
Citation [1] 667 0
Link [1] 667 0
Email [1] 667 0
Other [1] 667 0
Excerpt from Protocol describing participant treatment allocation
Attachment [1] 667 0
/Steps11and12/376527-(Uploaded-07-12-2018-17-46-10)-Study-related document.docx
Summary results
No Results