None listed
Conditions
Brief summary
This Phase 1, first-in-human, open-label, fixed-sequence, 3-period, 3-treatment study is designed to assess the skin safety, tolerability and PK of MRX-7MLL compared to the oral reference product, Namenda® (Memantine HCl oral tablet) or generic equivalent. This pilot study will also assess TDS adhesion, validate analytical methodology, assess inter- and intra-participant variability, and/or optimize PK sample collection timepoints for MRX-7MLL and oral memantine HCl tablets. The results of this study will support dose selection in future bioequivalence studies with MRX-7MLL and oral reference product or may be used to identify candidate formulation(s) for the pivotal study.
Interventions
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
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.
Sponsors
MedRx Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
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.
Outcome results
None listed