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

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

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

Study Overview

• Status: Terminated
• Conditions: Healthy; Gastric Retention
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom, NG11 6JS
      • Quotient Sciences (formerly Quotient Clinical)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male and female subjects.
2. Body mass index of 18.0 to 32.0 kg/m2.
3. Subjects must demonstrate their ability to swallow a test capsule at screening.
4. Must provide written informed consent.

Exclusion Criteria:

1. Subjects who have received any investigational medicinal product in a clinical research study within the previous 3 months.
2. Subjects who have previously been enrolled in this study.
3. History of any drug or alcohol abuse in the past 2 years.
4. Current smokers and those who have smoked within the last 12 months.
5. Individuals with clinically significant medical history relating to the gastrointestinal tract and potential for complications, thereof
6. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.
7. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
8. Individuals with contraindication to MRI imaging.

Other protocol defined criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lyndra Inc.
• Investigators: Study Director: Stuart Mair, MBChB, DRCOG, Quotient Clinical

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 26, 2017
• Primary Completion (ACTUAL): September 18, 2017
• Study Completion (ACTUAL): September 18, 2017

Study Registration Dates

• First Submitted: March 5, 2018
• First Submitted That Met QC Criteria: March 15, 2018
• First Posted (ACTUAL): March 16, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 5, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: QCL117924; 2017-000982-61 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No