Study Determining Gastric-Retentive and Modified Release Properties of Prototype Capsules in Healthy Subjects

Study Overview
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Brief Summary
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To assess how long modified release (MR) memantine hydrochloride prototype capsule formulations stay in the stomach as determined by magnetic resonance imaging (MRI).

Detailed Description
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This is a single center, open-label, single dose, 5-period study in 24 healthy male and female subjects, with an optional Period 6, if required. It is expected the study will be executed in 3 cohorts of 8 subjects, with each cohort participating in up to 2 study periods (total of up to 6 study periods). Cohort 3 may be conducted in parallel with Cohort 2. Subjects will be dosed in a sequential manner, as appropriate. Each subject will be administered up to 2 regimens (2 different prototype capsule formulations) across 2 study periods. There will be a minimum 35-day interval between each dose administration. Subjects will have an MRI scan performed on Days 2, 4, 7, 10 and 14 of each period to assess the gastric retentive properties of the formulation.

Official Title
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A Study Designed to Determine the Gastro-Retentive and Modified Release Properties of Memantine Hydrochloride (HCl) Prototype Capsule Formulations in Healthy Subjects

Conditions
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Gastric Retention, Healthy

Intervention / Treatment
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* Drug: Memantine Hydrochloride MR Prototype Capsule Formulation A
* Drug: Memantine Hydrochloride MR Prototype Capsule Formulation B
* Drug: Memantine Hydrochloride MR Prototype Capsule Formulation C
* Drug: Memantine Hydrochloride MR Prototype Capsule Formulation D
* Drug: Memantine Hydrochloride MR Prototype Capsule Formulation E
* Procedure: Magnetic Resonance Imaging


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 32.0 kg/m2. Subjects must demonstrate their ability to swallow a test capsule at screening. Must provide written informed consent. Exclusion Criteria: Subjects who have received any investigational medicinal product in a clinical research study within the previous 3 months. Subjects 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 last 12 months. Individuals with clinically significant medical history relating to the gastrointestinal tract and potential for complications, thereof Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients. Individuals with contraindication to MRI imaging. Other protocol defined criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Subjects will receive an oral administration of 50 mg of Memantine HCl prototype capsule formulation A; then formulation B; following each administration MRI will be performed for up to 14 days | Drug: Memantine Hydrochloride MR Prototype Capsule Formulation A<br>* Memantine HCl MR capsule formulation will be administered orally in a single dose<br>* Other names: Memantine HCl Capsule Formulation A (50 mg);Drug: Memantine Hydrochloride MR Prototype Capsule Formulation B<br>* Memantine HCl MR capsule formulation will be administered orally in a single dose<br>* Other names: Memantine HCl Capsule Formulation B (50 mg);Procedure: Magnetic Resonance Imaging<br>* MRI will be performed on specified days according to protocol<br>* Other names: MRI;|
| Experimental: Cohort 2<br>Subjects will receive an oral administration of 50 mg of Memantine HCl prototype capsule formulation C; then formulation D; following each administration MRI will be performed for up to 14 days | Drug: Memantine Hydrochloride MR Prototype Capsule Formulation C<br>* Memantine HCl MR capsule formulation will be administered orally in a single dose<br>* Other names: Memantine HCl Capsule Formulation C (50 mg);Drug: Memantine Hydrochloride MR Prototype Capsule Formulation D<br>* Memantine HCl MR capsule formulation will be administered orally in a single dose<br>* Other names: Memantine HCl Capsule Formulation D (50 mg);Procedure: Magnetic Resonance Imaging<br>* MRI will be performed on specified days according to protocol<br>* Other names: MRI;|
| Experimental: Cohort 3<br>Subjects will receive an oral administration of 50 mg of Memantine HCl prototype capsule formulation E; followed by MRI for up to 14 days | Drug: Memantine Hydrochloride MR Prototype Capsule Formulation E<br>* Memantine HCl MR capsule formulation will be administered orally in a single dose<br>* Other names: Memantine HCl Capsule Formulation E (50 mg);Procedure: Magnetic Resonance Imaging<br>* MRI will be performed on specified days according to protocol<br>* Other names: MRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric Retention by Magnetic Resonance Imaging (MRI) | Number of Participants with Gastric Retention by Magnetic Resonance Imaging (MRI), as measured after dosing | 7 Days |