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Trial registered on ANZCTR


Registration number
ACTRN12619001566123
Ethics application status
Approved
Date submitted
26/10/2019
Date registered
13/11/2019
Date last updated
16/11/2020
Date data sharing statement initially provided
13/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Food Effects of Single-Dose Memantine Hydrochloride and Donepezil Hydrochloride Extended Release Capsules in Healthy Volunteers
Scientific title
Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Food Effects of Single-Dose Memantine Hydrochloride and Donepezil Hydrochloride Extended Release Capsules in Healthy Volunteers
Secondary ID [1] 299642 0
LYN-157-C-002
Secondary ID [2] 299643 0
CM6219
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 314965 0
Condition category
Condition code
Neurological 313308 313308 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 315902 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 321788 0
Safety and tolerability of a LYN-157 capsule containing memantine hydrochloride and donepezil hydrochloride assessed from adverse event (AEs), i.e.,. AE solicitation/self report (e.g., nausea, headache, abdominal discomfort), directed physical exams, vital signs, safety laboratory assessments, electrocardiograms.
Timepoint [1] 321788 0
Adverse events will be collected at 6 and 12 hours and daily for 7 days during an inpatient admission for observation after dosing
Directed physical exams will be performed at the time of dose escalation (Day 1) and subsequently at Day 27 (admission to inpatient unit), Day 29 (prior to dosing and 12 hr post dose), Day 33, Day 36 and at outpatient visits (Day 38, 43, 50 and 57)
Vital signs will be collected prior to dosing and 4, 12 hrs post dose on Days 29 and 32. Otherwise, once daily while inpatient and at every clinic visit.
Safety labs will be assessed at admission and time of discharge from the inpatient clinic.
Electrocardiograms will be performed during dose escalation on Days 4, 8, 15; and pre-dose and 4 hrs post dose on Day 29 and thereafter on Days 32 and 35.
Primary outcome [2] 321789 0
While on steady state memantine and donepezil and after a single LYN-157 administration, pharmacokinetics of memantine by validated serum assay e.g., Cmax, Tmax, AUC(0-t)
Timepoint [2] 321789 0
Inpatient:
Day 28 and Day 29: Pre-dose and at 2, 4, 6, 8, 12 hours
Day 30 and Day 31:: Twice daily (every 12 hours, i.e., 24, 36, 48, 60)
Day 32 through Day 36: daily
Outpatient:
Days 38, 43, 50 and 57: daily
Primary outcome [3] 321790 0
While on steady state memantine and donepezil and after a single LYN-157 administration, pharmacokinetics of donepezil by validated serum assay e.g., Cmax, Tmax, AUC(0-t)
Timepoint [3] 321790 0
Inpatient:
Day 28 and Day 29: Pre-dose and at 2, 4, 6, 8, 12 hours
Day 30 and Day 31:: Twice daily (every 12 hours, i.e., 24, 36, 48, 60)
Day 32 through Day 36: daily
Outpatient:
Days 38, 43, 50 and 57: daily
Secondary outcome [1] 376210 0
Primary outcome: Effect of pre-dose food, i.e., fast, low- and high-fat meals, as assessed by the pharmacokinetics of a single dose of LYN-157 when administered to participants on steady state daily of memantine and donepezil, e.g,, Cmax, Tmax, AUC(0-t) and AUC(0-168).
Timepoint [1] 376210 0
Inpatient:
Day 28 and Day 29: Pre-dose and at 2, 4, 6, 8, 12 hours
Day 30 and Day 31:: Twice daily (every 12 hours, i.e., 24, 36, 48, 60)
Day 32 through Day 36: daily
Secondary outcome [2] 376499 0
Gastrointestinal transit of LYN-157 capsules by X-ray
Timepoint [2] 376499 0
Day 30 (24 hours post LYN-157 administration)
Day 35
Day 43

Eligibility
Key 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;
Minimum age
18 Years
Maximum age
49 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Participants will be block randomised to a pre-dose meal condition, by an electronic data capture system, at the time of admission to the inpatient clinic (Day 27). The three pre-dose meal conditions are as follows:
1) fasted
2) high fat meal
3) low fat meal
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
14/11/2019
Actual
14/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
36
Accrual to date
24
Final
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment hospital [1] 15042 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment hospital [2] 15043 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 28330 0
5000 - Adelaide
Recruitment postcode(s) [2] 28331 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 304116 0
Commercial sector/Industry
Name [1] 304116 0
Lyndra Australia Pty Ltd
Country [1] 304116 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Lyndra Australia Pty Ltd
Address
Level 13 41 Exhibition Street
Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 304331 0
None
Name [1] 304331 0
Address [1] 304331 0
Country [1] 304331 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304603 0
Bellberry Limited HREC Committee H
Ethics committee address [1] 304603 0
123 Glen Osmond Rd
Eastwood SA 5063
Ethics committee country [1] 304603 0
Australia
Date submitted for ethics approval [1] 304603 0
18/09/2019
Approval date [1] 304603 0
22/10/2019
Ethics approval number [1] 304603 0
2019-09-773

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97546 0
Prof Sepehr Shakib
Address 97546 0
CMAX
Level 5
18a North Terrace
Adelaide SA 5000
Country 97546 0
Australia
Phone 97546 0
+61 0870742823
Fax 97546 0
Email 97546 0
[email protected]
Contact person for public queries
Name 97547 0
Ms Jessica Ballinger
Address 97547 0
(Director)
Lyndra Australia Pty Ltd
Level 13
41 Exhibition Street
Melbourne VIC 3000
Country 97547 0
Australia
Phone 97547 0
+1 857 201 5322
Fax 97547 0
Email 97547 0
[email protected]
Contact person for scientific queries
Name 97548 0
Dr Bernard Silverman
Address 97548 0
Lyndra Therapeutics Inc
65 Grove St
Suite 301
Watertown MA 02472
Country 97548 0
United States of America
Phone 97548 0
+1 617 803 2445
Fax 97548 0
Email 97548 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data underlying published results only
When will data be available (start and end dates)?
3 months following publication, 4 years following publication
Available to whom?
case by case basis at the discretion of Lyndra (primary sponsor)
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
required to sign data access agreement by emailing primary sponsor ([email protected])


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.