Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000571178
Ethics application status
Approved
Date submitted
9/04/2019
Date registered
11/04/2019
Date last updated
8/10/2019
Date data sharing statement initially provided
11/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Memantine HCl and Donepezil HCl Extended Release Capsules in Healthy Volunteers
Scientific title
Phase 1, Open-Label Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Memantine HCl and Donepezil HCl Extended Release Capsules in Healthy Volunteers
Secondary ID [1] 297914 0
LYN-157-C-001
Secondary ID [2] 297915 0
CM2218
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer Disease 312300 0
Condition category
Condition code
Neurological 310859 310859 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) (40 mg) and donepezil HCl (38 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 40 mg memantine HCl and 38 mg donepezil HCl within the ER formulation (stellate). One capsule will be administered to the participant. This single capsule dose will be administered 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.
Intervention code [1] 314134 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319690 0
Safety and tolerability of a LYN-157 capsule containing memantine hydrochloride and donepezil hydrochloride assessed from a combination of the following: adverse event (AE’s) reporting, tracking of concomitant medications and examinations specified per protocol, e.g., safety laboratory tests, physical examinations, vital signs, ECGs, inspection of faeces for gross blood.
Timepoint [1] 319690 0
Adverse events and vital signs will be conducted daily for 8 days during an inpatient admission for observation after dosing. Directed physical exams will be performed at admission and on Days 1, 4, 8 and at the follow-up visits on Days 10, 15, 22 and 29 (End of Study). ECGs and safety laboratory assessments will be performed at admission and Days 4 and 7. Concomitant medications will be tracked at admission (Day -1), discharge from the unit (Day8) and at follow-up visits on Days 10, 15, 22 and 29 (End of study).
Primary outcome [2] 319691 0
Memantine pharmacokinetics [Cmax, Tmax, AUC(0-t)] by validated assay
Timepoint [2] 319691 0
Pre-dose, on day of dosing at 2, 4, 6, 8 and 12 hours post dosing, thereafter daily during inpatient admission through Day 8. After Day 8, participants will be discharged from the unit and will return for PK/blood sampling on Days 10, 15, 22 and 29 (End of Study).
Primary outcome [3] 319692 0
Donepezil pharmacokinetics [Cmax, Tmax, AUC(0-t)] by validated assay
Timepoint [3] 319692 0
Pre-dose, on day of dosing at 2, 4, 6, 8 and 12 hours post dosing, thereafter daily during inpatient admission through Day 8. After Day 8, participants will be discharged from the unit and will return for PK/blood sampling on Days 10, 15, 22 and 29 (End of Study).
Secondary outcome [1] 369192 0
Gastrointestinal transit of LYN-157 capsules by imaging [MRI or X-ray] assessments
Timepoint [1] 369192 0
Day 2 (Sentinel subjects only X-ray), MRI: Days 3, 5, 8; X-ray: Day 22, if required, i.e., if formulation components have not been retrieved by the time of discharge.

Eligibility
Key inclusion criteria
1) Healthy male and female participants
2) Body mass index of 18.0 to 30.0 kg/meters-squared
3) Suitable score for swallowing questionnaire
4) Demonstrate normal swallowing and gastrointestinal passage for capsules, as assessed while undergoing imaging studies
5) Must provide written informed consent
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) History of any drug or alcohol abuse in past 2 years
2) Current smokers and those who have smoked within the past 12 months
3) Individuals with clinically significant medical history related to the gastrointestinal tract and potential complications, thereof
4) Individuals with a positive test for HIV, hepatitis B or hepatitis C
5) Individuals who are contraindicated based on either memantine HCl or donepezil HCl
6) Serious adverse reaction or serious hypersensitivity to components of the study formulation or patency capsule
7) Individuals who have received any experimental agent within 30 days (or 5 half-lives), whichever is longer, prior to the date of dosing
8) Individuals with contraindication to MRI imaging
9) Individuals with functional constipation, irritable bowl or functional diarrhoea
10) Individuals with contraindications to elective X-ray based on known or expected radiation exposure

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
25/04/2019
Actual
26/04/2019
Date of last participant enrolment
Anticipated
9/05/2019
Actual
6/05/2019
Date of last data collection
Anticipated
8/06/2019
Actual
11/06/2019
Sample size
Target
8
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 13575 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 26223 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 302432 0
Commercial sector/Industry
Name [1] 302432 0
Lyndra Australia Pty Ltd
Country [1] 302432 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] 302333 0
None
Name [1] 302333 0
Address [1] 302333 0
Country [1] 302333 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303101 0
Bellberry Limited HREC Committee F
Ethics committee address [1] 303101 0
Ethics committee country [1] 303101 0
Australia
Date submitted for ethics approval [1] 303101 0
13/02/2019
Approval date [1] 303101 0
15/03/2019
Ethics approval number [1] 303101 0
2018-12-1072

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92474 0
Prof Sepehr Shakib
Address 92474 0
CMAX
Level 5
18a North Terrace
Adelaide SA 5000
Country 92474 0
Australia
Phone 92474 0
+61 0870742823
Fax 92474 0
Email 92474 0
[email protected]
Contact person for public queries
Name 92475 0
Jessica Ballinger
Address 92475 0
(Director)
Lyndra Australia Pty Ltd
Level 13
41 Exhibition Street
Melbourne VIC 3000
Country 92475 0
Australia
Phone 92475 0
+1 8572015322
Fax 92475 0
Email 92475 0
[email protected]
Contact person for scientific queries
Name 92476 0
Andrew Bellinger
Address 92476 0
Lyndra Therapeutics Inc
65 Grove Street
Suite 301
Watertown MA USA 02472
Country 92476 0
United States of America
Phone 92476 0
+19172041167
Fax 92476 0
Email 92476 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


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.