Alzheimer Disease, Gastric Retention, Healthy
Conditions
Brief summary
To assess how long memantine hydrochloride (HCl) (50 mg) extended release capsules stay in the stomach as determined by imaging assessment (MRI or abdominal ultrasound). To evaluate the safety of a memantine HCl extended release capsule formulation
Detailed description
This is a single centre, open label, single dose study in healthy adult subjects. Eligible individuals will be admitted to an inpatient unit in two or more cohorts. Enough eligible individuals will be admitted allowing for the enrollment of the Sentinel (n= 2) and Main Group (total of n=8 in Main), and an optional Supplemental Group (n= 6), if required. All enrolled subjects will be dosed with a single administration of an extended release capsule containing memantine hydrochloride (LYN-057), 50 mg. Dosing will be conducted in an inpatient clinical unit, with access to an acute care facility. Subjects will remain in the inpatient unit for 7 days after dosing. During this time, subjects will undergo intermittent imaging assessments for gastric retention \[magnetic resonance imaging (MRI) and abdominal ultrasound (U/S)\], safety assessments, blood sampling for evaluation of memantine pharmacokinetics (PK), and faecal collections for assessments of formulation components and bowel movement characteristics. Subjects will return to the clinic for PK sampling and safety assessments on Days 10, 15, 22 and Day 29 (End of Study Visit). In addition, some subjects may continue to perform faecal collection and/or may undergo imaging assessments on Day 10 based on clinical criteria. On Day 29 (End of Study Visit), subjects will undergo final safety and PK assessments and will be discharged from the study.
Interventions
DRUGLYN-057
Administration of single dose of LYN-057 presented as extended release capsule containing 50 mg of memantine hydrochloride (HCl)
PROCEDUREImaging Assessment (MRI)
Imaging assessments \[MRI\] will be performed on specified days according to protocol
PROCEDUREImaging Assessment (U/S)
Imaging assessments (abdominal U/S) will be performed on specified days according to protocol
Sponsors
Lyndra Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and female subjects 2. Body mass index of 18.0 to 30.0 kg/meters-squared 3. Suitable scores for two swallowing questionnaires 4. Demonstrate normal swallowing and gastrointestinal passage for capsule, as assessed while undergoing imaging studies 5. Must provide written informed consent
Exclusion criteria
1. Participants who have previously been enrolled in this study 2. History of any drug or alcohol abuse in the past 2 years 3. Current smokers and those who have smoked within the past 12 months 4. Individuals with clinically significant medical history relating to the gastrointestinal tract and potential complications, thereof 5. Individuals with a positive test for HIV, hepatitis B or hepatitis C 6. Individuals who are contraindicated based on memantine HCl 7. Serious adverse reaction or serious hypersensitivity to components of the study formulation or patency capsule 8. Individuals who have received any experimental agent within 30 days (or 5 half-lives), whichever is longer, prior to the date of dosing 9. Individuals with contraindication to MRI imaging 10. Individuals with functional constipation, irritable bowel, or functional diarrhea, as evaluated by standardized questionnaire 11. Individuals with contraindications to elective X-ray based on known or expected radiation exposure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastric retention by imaging assessment by MRI | Up to 9 days post-dosing | Visualization of formulation/formulation components in stomach by MRI |
| Gastric retention by imaging assessment by abdominal U/S | Up to 9 days post-dosing | Visualization of formulation/formulation components in stomach by abdominal U/S |
| Safety and tolerability of a single dose of LYN-057 extended release capsule | Through study completion, up to 3 months | Safety collected from a combination of the following: Adverse Event (AE) reporting and examinations specified per protocol |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Memantine HCl pharmacokinetics - Maximum Plasma Concentration (Cmax) | Pre-dose, on day of dosing at 2, 4, 6, 8 and 12 hours post-dosing, thereafter daily during inpatient stay through Day 8. After Day 8, PK sampling on Day 10, 15, 22 and 29. | Memantine HCl pharmacokinetics - Cmax by validated assay |
| Physical features of recovered formulation components | Through study completion, up to 29 days | Recording of the descriptive physical features, e.g. number of polymeric arms (if separate) or attached to the core, of formulation components recovered from collected fecal specimens |
| Memantine HCl pharmacokinetics - Time after administration of maximum plasma concentration (Tmax) | Pre-dose, on day of dosing at 2, 4, 6, 8 and 12 hours post-dosing, thereafter daily during inpatient stay through Day 8. After Day 8, PK sampling on Day 10, 15, 22 and 29. | Memantine HCl pharmacokinetics - Tmax by validated assay |
| Memantine HCl pharmacokinetics - Area Under the Curve (AUC) | Pre-dose, on day of dosing at 2, 4, 6, 8 and 12 hours post-dosing, thereafter daily during inpatient stay through Day 8. After Day 8, PK sampling on Day 10, 15, 22 and 29. | Memantine HCl pharmacokinetics - AUC by validated assay |
Countries
Australia
Outcome results
None listed