Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001274561p
Ethics application status
Submitted, not yet approved
Date submitted
1/10/2024
Date registered
18/10/2024
Date last updated
18/10/2024
Date data sharing statement initially provided
18/10/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 Open-label Skin Safety, Tolerability and Pharmacokinetic Study of MRX-7MLL (Memantine Transdermal Delivery System) in Healthy Adults
Scientific title
A Phase 1 Open-label Skin Safety, Tolerability and Pharmacokinetic Study of MRX-7MLL (Memantine Transdermal Delivery System) in Healthy Adults
Secondary ID [1] 312915 0
MRX-7MLL-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's dementia 335077 0
Condition category
Condition code
Neurological 331581 331581 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will recieve the following:
In Period 1 (Treatment A), all 16 participants will be administered a single 10 mg memantine HCL tablet in the morning and another 4 hours later on Day 1 (20 mg/day).

In Period 2 (Treatment B), all 16 participants will have a single MRX-7MLL Transdermal Delivery System (TDS) applied, on the morning of Day 1 (Study Day 17). The TDS for this period contains 6.65mg of memantine HCL. The TDS will be applied to intact skin only on the lateral surface of the upper arm. The wear time will be 7 days (168 hours). The TDS will be removed on the morning of Day 8 (Study Day 24).

Following the completion of Period 2, a Safety Review Committee (SRC) will be convened to review available skin safety and tolerability data. In the event that the skin safety and tolerability of Period 2 is determined to be acceptable by the SRC, all 16 participants will proceed to Period 3.

In Period 3 , all 16 participants will have a single MRX-7MLL TDS 5.0% applied on the morning of Day 1 (Study Day 40). The TDS for this period contains 13.30mg of memantine HCL. The TDS will be applied to intact skin only on the lateral surface of the upper arm. The wear time will be 7 days (168 hours). The TDS will be removed on the morning of Day 8 (Study Day 47).

Participants are administered all study medication by the site staff at the site. The application site will be routinely checked for adherence and participants will be advised to inform site staff if the TDS becomes loose or detaches during the wear period.
Intervention code [1] 329448 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339320 0
To evaluate the dermal irritancy of 2 test strengths/dose levels of MRX-7MLL (2.5% and 5.0%, containing 6.65 mg and 13.30 mg of memantine HCl, respectively) in healthy adult participants
Timepoint [1] 339320 0
Skin Irritation Assessment and Photograph of Skin Area will be performed predose on Day 1 of Period 2 (Study Day 17, within 3 hours before TDS application) and 8 hours (±1 hour) after TDS application. On Days 2 through 7 of Period 2 (Study Days 18 through 23), Skin Irritation Assessment and Photograph of Skin Area will be performed once daily at the same time as Day 1 TDS application (± 1 hour). On Day 8 of Period 2 (Study Day 24), Skin Irritation Assessment and Photograph of Skin Area will be performed at 30 minutes (±10 min) after removal of the patch, and then at 24 hours (±12 hours), 48 hours (±12 hours), and 72 hours (±12 hours) after removal of the TDS on an outpatient basis.

Skin Irritation Assessment and Photograph of Skin Area will be performed predose on Day 1 of Period 3 (Study Day 40, within 3 hours before TDS application) and 8 hours (±1 hour) after TDS application. On Days 2 through 7 of Period 3 (Study Days 41 through 46), Skin Irritation Assessment and Photograph of Skin Area will be performed once daily at the same time as Day 1 TDS application (± 1 hour). On Day 8 of Period 3 (Study Day 47), Skin Irritation Assessment and Photograph of Skin Area will be performed at 30 minutes (±10 min) after removal of the patch, and then at 24 hours (±12 hours), 48 hours (±12 hours), and 72 hours (±12 hours) after removal of the TDS on an outpatient basis.
Primary outcome [2] 339321 0
To evaluate the pharmacokinetics (PK) of 2 test strengths/dose levels of MRX-7MLL (2.5% and 5.0%, containing 6.65 mg and 13.30 mg of memantine HCl, respectively) in comparison to oral memantine tablets in healthy adult participants
Timepoint [2] 339321 0
Period 1 - Blood samples for PK analysis will be collected at predose (within 2 hours before AM study drug administration) and at 2 (±10 min), 4 (±10 min, must be before PM study drug administration), 6 (±15 min), 8 (±15 min), 10 (±15 min), 12 (±30 min), 24 (±30 min), 48 (±1 hour), 72 (±1 hour), and 168 (±1 hour) hours after the AM study drug administration.

Period 2 - Blood samples for PK analysis will be collected at predose (within 2 hours before TDS application) and 6 (±15 min), 12 (±30 min), 24 (±30 min), 48 (±1 hour), 96 (±1 hour), and 168 (±1 hour) after TDS application, then at 192 (±12 hours), 216 (±12 hours), 264 (±12 hours), and 312 (±12 hours) hours after TDS application on an outpatient basis.

Period 3 - Blood samples for PK analysis will be collected at predose (within 2 hours before TDS application) and 6 (±15 min), 12 (±30 min), 24 (±30 min), 48 (±1 hour), 96 (±1 hour), and 168 (±1 hour) after TDS application, then at 192 (±12 hours), 216 (±12 hours), 264 (±12 hours), and 312 (±12 hours) hours after TDS application on an outpatient basis.
Secondary outcome [1] 439448 0
To evaluate the safety and tolerability of MRX-7MLL 2.5% containing 6.65 mg of memantine HCl, in comparison with oral memantine tablets, in healthy adult participants.
Timepoint [1] 439448 0
1. All AEs will be collected on a daily basis from the time of first Period 2 study drug administration until the end of Period 2.
2. Changes from baseline assessments with be monitored at the following timepoints:
• Vital signs - 16 - 30
• Physical Examinations - 16, 20 & 24
• ECGs - Screening, Day 17
• C-SSRS - Screening, Day 16 & 30
• Clinical Lab Safety Tests - Screening, Day 16 & 23
Secondary outcome [2] 440518 0
To evaluate the safety and tolerability of MRX-7MLL 5.0%, containing 13.30 mg of memantine HCl in comparison with oral memantine tablets in healthy adult participants.
Timepoint [2] 440518 0
1. All AEs will be collected on a daily basis from the time of first Period 3 study drug administration until the End of Study visit.
2. Changes from baseline assessments with be monitored at the following timepoints:
• Vital signs - Day 39 - 53
• Physical Examinations – Day 39, 43 & 47
• ECGs – Day 40
• C-SSRS - Screening, Day 39 & 53
• Clinical Lab Safety Tests - Screening, Day 39 & 46

Eligibility
Key inclusion criteria
1. Healthy adult male or female, 18 to 55 years of age inclusive at Screening.
2. Female of childbearing potential and male participants must follow protocol specified contraception guidance.
3. Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to Study Day 1 based on participant self-reporting.
4. Body mass index (BMI) greater than or equal to 18.0 and less than or equal to 32.0 kg per m2 at Screening.
5. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the Investigator or designee.
6. Must agree to refrain during confinement from the use of make-up, creams, lotions, powders, or other topical products on the skin area where the TDS will be placed.
7. Must agree to avoid any excessive sun exposure during the conduct of the study.
8. Has sufficient frame size and clear skin at time of Screening and Study Day -1 for TDS applications, as deemed by the Investigator or designee.
9. Skin type with Fitzpatrick scale score of I, II, or III, or have skin colorimeter scores equivalent to the allowed Fitzpatrick skin type.
10. Understands the study procedures in the informed consent form (ICF) and be willing and able to comply with the protocol.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Is mentally or legally incapacitated or has significant emotional problems at the time of Screening or expected during the conduct of the study.
2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator or designee.
3. History of any illness that, in the opinion of the Investigator or designee, might confound the results of the study or poses an additional risk to the participants by their participation in the study.
4. History or presence of alcohol or drug abuse within the 2 years prior to Study Day 1.
5. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds or adhesive materials.
6. Medical history of significant dermatologic disease or conditions such as atopy, psoriasis, vitiligo, or condition known to alter skin appearance or physiologic response (e.g., diabetes, porphyria).
7. Obvious difference in skin color between application sites or the presence of a skin condition, excessive hair at the application sites, scar tissue, tattoo, open sores, raised moles, damaged skin in or around application sites (including sunburn, uneven skin tones), body piercings, or other disfigurations that would interfere with placement of TDSs, skin assessment, drug absorption, or reactions to drug, in the opinion of the Investigator or qualified designee.
8. Female participants with a positive pregnancy test at Screening or Study Day -1, or who are lactating.
9. Positive urine drug or alcohol results at Screening or Study Day -1.
10. Positive results at Screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
11. Any positive responses on the C-SSRS at Screening or Study Day -1.
12. Unable to refrain from or anticipates the use of:
• Any drug, including prescription and non-prescription medications, antacids, urinary pH modifiers, herbal remedies, or vitamin supplements beginning 7 days prior to Study Day 1;
• Any use of systemic steroid or nonsteroidal anti-inflammatory drugs or topical analgesics, antihistamines or any topical product (including non-medicated products) on the TDS application sites 72 hours before the first TDS application. However, acetaminophen (up to 2 g per 24 hours) may be used post-TDS application, at the discretion of the Investigator or designee.
• Note: Medication listed as part of acceptable birth control methods (refer to Section 10.4), hormonal replacement therapy, and thyroid medication will be allowed.
13. Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 24 hours prior to check-in on Study Day -1 and throughout the study.
14. Donation of blood or significant blood loss within 56 days prior to Study Day 1.
15. Plasma donation within 7 days prior to Study Day 1.
16. Participation in another clinical study within 30 days prior to Study Day 1.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
27/11/2024
Actual
Date of last participant enrolment
Anticipated
31/01/2025
Actual
Date of last data collection
Anticipated
1/04/2025
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 317347 0
Commercial sector/Industry
Name [1] 317347 0
MEDRx Australia Pty Ltd
Country [1] 317347 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
MedRx Australia Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 319634 0
Commercial sector/Industry
Name [1] 319634 0
Inclin Pty Ltd
Address [1] 319634 0
Country [1] 319634 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 316077 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 316077 0
Ethics committee country [1] 316077 0
Australia
Date submitted for ethics approval [1] 316077 0
25/09/2024
Approval date [1] 316077 0
Ethics approval number [1] 316077 0

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

Contacts
Principal investigator
Name 136706 0
Dr Christopher Argent
Address 136706 0
Scientia Clinical Research Ltd The Bright Building, Levels 5 & 6, Corner High & Avoca Streets, Randwick NSW 2031
Country 136706 0
Australia
Phone 136706 0
+61 02 9382 5800
Fax 136706 0
Email 136706 0
[email protected]
Contact person for public queries
Name 136707 0
Christopher Argent
Address 136707 0
Scientia Clinical Research Ltd The Bright Building, Levels 5 & 6, Corner High & Avoca Streets, Randwick NSW 2031
Country 136707 0
Australia
Phone 136707 0
+61 02 9382 5800
Fax 136707 0
Email 136707 0
[email protected]
Contact person for scientific queries
Name 136708 0
Christopher Argent
Address 136708 0
Scientia Clinical Research Ltd The Bright Building, Levels 5 & 6, Corner High & Avoca Streets, Randwick NSW 2031
Country 136708 0
Australia
Phone 136708 0
+61 02 9382 5800
Fax 136708 0
Email 136708 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


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.