None listed
Conditions
Brief summary
An open-label, multi-centre study in healthy volunteers: To determine the safety and tolerability of LYN-157 when administered as a single dose to participants on steady-state daily memantine HCl and donepezil HCl. To characterize the pharmacokinetics (PK) of memantine HCl and donepezil when LYN-157 is administered as a single dose to participants on steady-state daily memantine HCl and donepezil HCl. To assess the effect of pre-dose food (i.e., fasted, low and high-fat meals) on memantine HCl and donepezil HCl PK following a single dose of LYN-157 to participants on steady-state daily memantine HCl and donepezil HCl.
Interventions
The intervention is LYN-157, a extended release (ER) prototype capsule containing memantine hydrochloride (HCl) (170 mg) and donepezil HCl (70 mg). The rationale for the development of this ER formulation is to reduce the frequency of dosing orally administered memantine and donepezil HCl medications to once weekly or less and thereby improving the management of Alzheimer's disease.
The dose of LYN-157 to be given is a single Size 00EL capsule containing 170 mg memantine HCl and 70 mg donepezil
The intervention is LYN-157, a extended release (ER) prototype capsule containing memantine hydrochloride (HCl) (170 mg) and donepezil HCl (70 mg). The rationale for the development of this ER formulation is to reduce the frequency of dosing orally administered memantine and donepezil HCl medications to once weekly or less and thereby improving the management of Alzheimer's disease. The dose of LYN-157 to be given is a single Size 00EL capsule containing 170 mg memantine HCl and 70 mg donepezil HCl within the ER formulation (stellate). One capsule will be administered to the participant. Dose titration over 28 days of the combination of a daily memantine HCl extended release oral capsule to 28 mg and a donepezil HCl oral tablet to 10 mg, will be accomplished according to the following regimen as oral administration: Regimen 1: Day 1-3 (7 mg memantine, 5 mg donepezil) Regimen 2: Day 4-7 (14 mg memantine, 5 mg donepezil) Regimen 3: Day 8-14 (21 mg memantine, 10 mg donepezil) Regimen 4: Day 15-28 (28 mg memantine, 10 mg donepezil). Each participant will have a clinic visit on the first day of each of the dosing regimens (and Day 22), where the respective doses will be self-administered with a trained nurse (at a minimum) present. Until the remainder of the regimen, the participant will orally self-administer daily at home, with calls from the clinic to verify adherence, then return to the clinic for the next scheduled regimen (also Day 22) or entry to the inpatient unit. Following the completion of the dose titration regimens, all participants will receive a single capsule dose of LYN-157 which will be administered (after fasting, a low fat meal or a high fat meal) by a trained nurse (at a minimum) in a clinic for both Sentinel and Main, if required, dropouts will be replaced at the discretion of the PI. Participants will be randomised at the time of admission to the inpatient clinic (Day 27). Block randomisation will be associated with the administration condition (fasted, low- or high-fat meal) pre-dose and defined by the electronic data capture system.
Sponsors
Lyndra Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated informed consent; 2. Stated willingness to comply with all protocol-specified procedures and availability for the duration of the study; 3. Good current health, in the opinion of the Investigator, as evidenced on review of medical history, no significant gastrointestinal abnormalities, physical examination, concomitant medications, and other safety assessments. 4.. Body mass index (BMI) of greater than or equal to 18 kg/meters-squared and less than or equal to 30 kg/meters-squared 5. Body weight of greater than or equal to 55 kg;
Exclusion criteria
1. Any known clinically significant oesophageal or gastrointestinal disease; 2. Unsuitable score for swallowing questionnaire; 3. Do not demonstrate normal swallowing and gastrointestinal passage for capsule, as assessed while undergoing imaging studies; 4. Symptoms suggestive of irritable bowel syndrome, functional constipation or functional diarrhoea; 5. History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs; 6. Clinically significant abnormal safety (e.g., physical examination) or safety laboratory assessments; 7. Active hepatitis B, hepatitis C, or H. pylori infection at Screening, unless there is a confirmed medical history of successful treatment; 8. Use of prescription medications, natural remedies, vitamins or non-prescription (over the counter) medicines associated with changes to gastric motility or pH or management of gastrointestinal symptoms within two weeks of study dosing; 9. Individuals who are contraindicated based on memantine HCl or donepezil HCl; 10. History of any drug or alcohol abuse in the past 2 years; 11. Individuals of reproductive potential who are (hetero) sexually active but unwilling to use acceptable means of contraception through the End of Study; 12. Individuals who are nursing or who have positive or indeterminate pregnancy test.
Outcome results
None listed