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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy; Alzheimer Disease; Gastric Retention
• Intervention / Treatment: Drug: LYN-057; Procedure: Imaging Assessment (MRI); Procedure: Imaging Assessment (U/S)

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sentinel/Main; 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; Administration of single dose of LYN-057 presented as extended release capsule containing 50 mg of memantine hydrochloride (HCl); Other Names: LYN-057 (50 mg); Procedure: Imaging Assessment (MRI); Imaging assessments [MRI] will be performed on specified days according to protocol; Other Names: MRI; Procedure: Imaging Assessment (U/S); Imaging assessments (abdominal U/S) will be performed on specified days according to protocol; Other Names: Abdominal Ultrasound

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lyndra Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2018
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): November 13, 2018

Study Registration Dates

• First Submitted: October 14, 2018
• First Submitted That Met QC Criteria: October 16, 2018
• First Posted (Actual): October 19, 2018

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: LYN-057-C-002; ACTRN12618001426279 (Registry Identifier: ANZCTR); CM8718 (Other Identifier: CMAX)

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