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Trial registered on ANZCTR


Registration number
ACTRN12619001513101
Ethics application status
Approved
Date submitted
21/10/2019
Date registered
1/11/2019
Date last updated
22/04/2020
Date data sharing statement initially provided
1/11/2019
Date results information initially provided
30/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacokinetics and Safety of Rivastigmine Nasal Spray versus Exelon (Registered Trademark) Capsule in Healthy Men
Scientific title
A Randomised, Crossover, Two Period, Pharmacokinetic, Bioavailability and Safety Study of a Single Dose of the Novel Rivastigmine Nasal Spray and Single Dose Rivastigmine (Exelon, Registered Trademark) Oral Capsule in Young Healthy Adult Males
Secondary ID [1] 299588 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's disease 314868 0
Condition category
Condition code
Neurological 313210 313210 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment A: Rivastigmine Nasal Spray 4mg as single dose (One spray each nostril)
Treatment B: Exelon (Registered Trademark) 3mg oral capsule as single dose
Participants randomised to receive each treatment as a crossover with a single dose given on the first day, followed by a 2-day washout and a single dose given on the fourth day. Treatments administered by site staff to participants under direct supervision.
Intervention code [1] 315842 0
Treatment: Drugs
Intervention code [2] 315843 0
Treatment: Devices
Comparator / control treatment
Comparator: Treatment B: Exelon (Registered Trademark) 3mg oral capsule as single dose
Control group
Active

Outcomes
Primary outcome [1] 321715 0
Pharmacokinetics: Cmax, tmax, AUC0-last, AUC0-infinity, t1/2 and terminal elimination rate constant,

Plasma assay for rivastigmine and its' primary metabolite (NAP 226-90) and pharmacokinetic parameters calculated using noncompartmental pharmacokinetic analysis. Inferential statistics on the natural log-transformed (ln) pharmacokinetic parameters (Cmax, AUC0-last, AUC0-infinity) will be performed using the 3mg oral dose as reference.
Timepoint [1] 321715 0
Nasal: Pre-dose, 5, 10, 15, 30, 45, 60, 90 mins; 2, 3, 4, 6, 8, 10, 12 and 24 h
Oral: Pre-dose, 15, 30, 45, 60, 90 mins; 2, 3, 4, 6, 8, 10, 12, 15 and 24 h
Secondary outcome [1] 375995 0
Safety: Adverse events reporting, visual nasal mucosal examination and healthy screen pre- and poststudy.

Healthy screen includes: Physical examination, including vital signs (blood pressure, heart rate, respiratory rate and temperature) and ECG. Urinalysis for general health (urine pH, blood, protein, ketones, leukocyte elastase, nitrates, glucose, Specific gravity, urobilinogen and bilirubin) and any drugs of addiction*. Blood collected for clinical laboratory analysis (serum chemistry and haematology) and analysis for HIV*, hepatitis B*, and hepatitis C* analysis. Normal ranges for clinical laboratory parameters will be as per the local laboratory definitions.
*Pre-study
Timepoint [1] 375995 0
Visual nasal mucosal examination at screening, check-in, pre-nasal-dose and 24 hours postnasal-dose.
Adverse events are monitored from Day 1 until Day 5 (24 hours post-dose) and at follow-up visit (Day 9 +/- 1).
Healthy screens are undertaken at screening, admission (Day -1) and on Day 5 (24 hours post-dose).

Eligibility
Key inclusion criteria
- Healthy males between 18 and 55 years (inclusive) of age.
- No known history of clinically significant liver, neurological, renal, cardiovascular, respiratory (asthma), endocrinological, gastrointestinal, haematopoietic disease, neoplasm or any other clinically significant medical disorder, which in the Investigator's judgment contraindicate administration of the study interventions.
- BMI 18-32 (inclusive) calculated as Weight (Kg)/Height (sq.m).
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Known hypersensitivity to rivastigmine, components (benzyl alcohol, benzoates), other carbamates or ondansetron.
- Current symptomatic allergic rhinitis.
- Presence of significant disease or anatomical abnormality affecting the nasal passages.
- History of or currently active asthma or chronic obstructive pulmonary disease, excluding childhood asthma.
- Use of any prescription, OTC or herbal medication within 7 days or 5 half-lives (whichever is longer) of study drug administration, with the exception of the oral contraceptive pill, paracetamol up to 2g daily and low-moderate dose NSAID.
- History of or currently active cardiac arrhythmias such as bradycardia and sick sinus syndrome.
- History of heart block or disease of cardiac conducting system.
- History of urinary tract obstruction.
- History of or currently active GI diseases such as peptic ulcer, GERD, bleeding or history of any GI surgery other than appendectomy or herniotomy, or with any gastrointestinal disorder likely to influence drug absorption, or with any history of anorexia, frequent nausea or emesis, regardless of aetiology.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 15002 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 28287 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 304070 0
Commercial sector/Industry
Name [1] 304070 0
Lachesis Biosciences Ltd
Address [1] 304070 0
Lvl 13, 664 Collins St, Docklands VIC 3008
Country [1] 304070 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Lachesis Biosciences Ltd
Address
Lvl 13, 664 Collins St, Docklands VIC 3008
Country
Australia
Secondary sponsor category [1] 304265 0
None
Name [1] 304265 0
Address [1] 304265 0
Country [1] 304265 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304561 0
The Alfred Health Human Ethics Committee
Ethics committee address [1] 304561 0
The Alfred Hospital, Commercial Road, Melbourne, Victoria, 3004
Ethics committee country [1] 304561 0
Australia
Date submitted for ethics approval [1] 304561 0
21/10/2019
Approval date [1] 304561 0
25/11/2019
Ethics approval number [1] 304561 0
639/19

Summary
Brief summary
Rivastigmine (RIV) is an acetylcholine esterase inhibitor which prevents neurotransmitter breakdown. As such it is currently approved for the treatment of neurological disorders such as Alzheimer's and Parkinson's disease dementia. RIV is available in two forms, oral (capsule) and as a transdermal (through the skin) patch. The latter was developed as a consequence of the oral forms causing nausea, vomiting and diarrhoea predominantly caused by the low oral bioavailability of this drug. Although the transdermal patch overcomes a lot of these side effects, a high percentage of people suffer from skin irritation and possible sleeplessness. This study will investigate whether delivering RIV nasally (into the nose) provides RIV therapeutic levels in the blood plasma that are comparable to Exelon (Registered Trademark) oral capsule and whether nasal RIV results in lower side effects. Each intervention will be as a single dose with thorough blood sampling over 24 hours to assess drug levels; each intervention will be separated by a 2 day washout period. This is a phase 1 trial in 16 young healthy males aged 18 to 55 years. While comparing the two delivery methods, this study will also investigate the safety and tolerability of Rivastigmine nasal spray.
Trial website
Trial related presentations / publications
Public notes
Exelon is a Registered Trademark of Novartis Corporation.

Contacts
Principal investigator
Name 97390 0
Dr Ben Snyder
Address 97390 0
Nucleus Network Pty Ltd, Level 5, Burnet Tower, 89 Commercial Road Melbourne, VIC 3004
Country 97390 0
Australia
Phone 97390 0
+61 3 9076 8900
Fax 97390 0
Email 97390 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 97391 0
Dr Ben Snyder
Address 97391 0
Nucleus Network Pty Ltd, Level 5, Burnet Tower, 89 Commercial Road Melbourne, VIC 3004
Country 97391 0
Australia
Phone 97391 0
+61 1800 243 733
Fax 97391 0
Email 97391 0
reply@nucleusnetwork.com.au
Contact person for scientific queries
Name 97392 0
Mr Timothy Morgan, PhD
Address 97392 0
Lachesis Biosciences Ltd, Lvl 13, 664 Collins St, Docklands VIC 3008
Country 97392 0
Australia
Phone 97392 0
+61 3 5561 7758
Fax 97392 0
Email 97392 0
tim.morgan@lachesisbio.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary