Clinical trial NCT03711825: Study to Evaluate Safety/Duration in Stomach of Extended Release Capsules Containing Memantine Hydrochloride in Healthy Adults
Official title: An Open Label Study to Evaluate the Safety and Gastric-Retentive Properties of Modified Release Capsules Containing Memantine Hydrochloride in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Alzheimer Disease
Gastric Retention
Healthy
Lead sponsor: Lyndra Inc.
Sponsor class: INDUSTRY
First posted: 2018-10-19
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Gastric retention by imaging assessment by MRI
timeFrame: Up to 9 days post-dosing
measure: Gastric retention by imaging assessment by abdominal U/S
timeFrame: Up to 9 days post-dosing
measure: Safety and tolerability of a single dose of LYN-057 extended release capsule
timeFrame: Through study completion, up to 3 months
Secondary outcomes:
measure: Memantine HCl pharmacokinetics - Maximum Plasma Concentration (Cmax)
timeFrame: 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.
measure: Memantine HCl pharmacokinetics - Time after administration of maximum plasma concentration (Tmax)
timeFrame: 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.
measure: Memantine HCl pharmacokinetics - Area Under the Curve (AUC)
timeFrame: 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.
measure: Physical features of recovered formulation components
timeFrame: Through study completion, up to 29 days
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX
state: South Australia
Study officials:
affiliation: CMAX
name: Sepehr Shakib, MD
role: PRINCIPAL_INVESTIGATOR
References: