Study to Evaluate Safety/Duration in Stomach of Extended Release Capsules Containing Memantine Hydrochloride in Healthy Adults

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open Label Study to Evaluate the Safety and Gastric-Retentive Properties of Modified Release Capsules Containing Memantine Hydrochloride in Healthy Adults

Conditions
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Alzheimer Disease, Gastric Retention, Healthy

Intervention / Treatment
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* Drug: LYN-057
* Procedure: Imaging Assessment (MRI)
* Procedure: Imaging Assessment (U/S)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects Body mass index of 18.0 to 30.0 kg/meters-squared Suitable scores for two swallowing questionnaires Demonstrate normal swallowing and gastrointestinal passage for capsule, as assessed while undergoing imaging studies Must provide written informed consent Exclusion Criteria: Participants who have previously been enrolled in this study History of any drug or alcohol abuse in the past 2 years Current smokers and those who have smoked within the past 12 months Individuals with clinically significant medical history relating to the gastrointestinal tract and potential complications, thereof Individuals with a positive test for HIV, hepatitis B or hepatitis C Individuals who are contraindicated based on memantine HCl Serious adverse reaction or serious hypersensitivity to components of the study formulation or patency capsule Individuals who have received any experimental agent within 30 days (or 5 half-lives), whichever is longer, prior to the date of dosing Individuals with contraindication to MRI imaging Individuals with functional constipation, irritable bowel, or functional diarrhea, as evaluated by standardized questionnaire Individuals with contraindications to elective X-ray based on known or expected radiation exposure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sentinel/Main<br>Sentinel dosing of two subjects in clinic of LYN-057 (50 mg), followed by Main, i.e. remaining 6 subjects, for total of 8 subjects doses; followed by imaging assessment (MRI/abdominal U/S) | Drug: LYN-057<br>* Administration of single dose of LYN-057 presented as extended release capsule containing 50 mg of memantine hydrochloride (HCl)<br>* Other names: LYN-057 (50 mg);Procedure: Imaging Assessment (MRI)<br>* Imaging assessments [MRI] will be performed on specified days according to protocol<br>* Other names: MRI;Procedure: Imaging Assessment (U/S)<br>* Imaging assessments (abdominal U/S) will be performed on specified days according to protocol<br>* Other names: Abdominal Ultrasound;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric retention by imaging assessment by MRI | Visualization of formulation/formulation components in stomach by MRI | Up to 9 days post-dosing | 
| Gastric retention by imaging assessment by abdominal U/S | Visualization of formulation/formulation components in stomach by abdominal U/S | Up to 9 days post-dosing | 
| Safety and tolerability of a single dose of LYN-057 extended release capsule | Safety collected from a combination of the following: Adverse Event (AE) reporting and examinations specified per protocol | Through study completion, up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Memantine HCl pharmacokinetics - Maximum Plasma Concentration (Cmax) | Memantine HCl pharmacokinetics - Cmax by validated assay | 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 - Time after administration of maximum plasma concentration (Tmax) | Memantine HCl pharmacokinetics - Tmax by validated assay | 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 - Area Under the Curve (AUC) | Memantine HCl pharmacokinetics - AUC by validated assay | 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. | 
| Physical features of recovered formulation components | 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 | Through study completion, up to 29 days |