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Trial registered on ANZCTR


Registration number
ACTRN12614001313628
Ethics application status
Approved
Date submitted
8/12/2014
Date registered
16/12/2014
Date last updated
30/06/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of the Pharmacokinetics and Safety of Rivastigmine Intranasal Spray
Scientific title
A Sequential, Crossover, Pharmacokinetic and Safety Study of Single Dose Rivastigmine Intranasal Spray (3.126mg) and Single Dose Intravenous Solution (1mg) to Evaluate the Absolute Bioavailability of Rivastigmine Intranasal Spray in Healthy Elderly Volunteers
Secondary ID [1] 285796 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's disease 293689 0
Condition category
Condition code
Neurological 293988 293988 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: First day, Intravenous Rivastigmine 1mg (delivered by infusion pump over 30 minutes) followed by a 2-day washout

Arm 2: Fourth day, Rivastigmine Intranasal Spray 3.126mg as single dose (One spray each nostril)
Intervention code [1] 290762 0
Treatment: Drugs
Intervention code [2] 290763 0
Treatment: Devices
Comparator / control treatment
Arm 1: Intravenous Rivastigmine 1mg
Control group
Active

Outcomes
Primary outcome [1] 293762 0
Pharmacokinetics: F, Cmax, tmax, AUC0-infinity, t1/2, Cavg

Plasma assay for rivastigmine and its' primary metabolite (NAP 226-90) and pharmacokinetic parameters calculated using noncompartmental pharmacokinetic analysis.
Timepoint [1] 293762 0
Nasal: Pre-dose, 5, 10, 15, 30, 60, 90 mins; 2, 3, 4, 6, 8, 10, 12 and 24 h
IV: Pre-dose, 10, 20, 30, 45, 60, 75, 90 mins; 2, 3, 4, 6, 8, 12 and 24 h
Secondary outcome [1] 311770 0
Safety: Adverse events reporting, visual nasal mucosal examination and healthy screen pre- and post-study

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] 311770 0
Visual nasal mucosal examination at screening, check-in, day 4 (pre-nasal-dose) and day 5 (24 hours post-nasal-dose).

Adverse events are monitored from Day 1 until Day 5 (24 hours post-nasal-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-nasal-dose).

Eligibility
Key inclusion criteria
- Healthy Caucasian males and females between 55 and 85 years (inclusive) of age.
- No known history of clinically significant neurological, renal, cardiovascular, respiratory (asthma), endocrinological, gastrointestinal, haematopoietic disease, neoplasm or any other clinically significant medical disorder, which in the Principal Investigator's judgment contraindicate administration of the study interventions.
- BMI 18-32 (inclusive) calculated as Weight (Kg)/Height (sq.m).
Minimum age
55 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Known hypersensitivity to the drug, components (benzyl alcohol, benzoates) or other carbamates.
- Current symptomatic allergic rhinitis
- History of or currently active asthma or chronic obstructive pulmonary disease, excluding childhood asthma.
- History of or currently active cardiac arrhythmias such as bradycardia and sick sinus syndrome.
- 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 etiology.
- Use of any beta-blocker class prescription drug, cholinomimetic and anticholinergic drugs, including atropine, tricyclic antidepressants and anti-histamines.

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
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] 3236 0
The Alfred - Prahran
Recruitment postcode(s) [1] 9016 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 290358 0
Commercial sector/Industry
Name [1] 290358 0
Lachesis Biosciences Pty Ltd
Address [1] 290358 0
24 Mickle Crescent, Warrnambool VIC 3280
Country [1] 290358 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Lachesis Biosciences Pty Ltd
Address
24 Mickle Crescent, Warrnambool VIC 3280
Country
Australia
Secondary sponsor category [1] 289081 0
None
Name [1] 289081 0
Address [1] 289081 0
Country [1] 289081 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292062 0
The Alfred Health Human Ethics Committee
Ethics committee address [1] 292062 0
The Alfred Hospital, Commercial Road, Melbourne, Victoria, 3004
Ethics committee country [1] 292062 0
Australia
Date submitted for ethics approval [1] 292062 0
26/11/2014
Approval date [1] 292062 0
19/12/2014
Ethics approval number [1] 292062 0
538/14

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. RIV is available in two forms, oral (capsule and liquid) 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 intranasally (into the nose), results in lower side effects, while maintaining the desired therapeutic effect. As such this study will compare the bioavailability of intranasal delivery to intravenous delivery of RIV at a level that is reported to be therapeutically beneficial. 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 an exploratory phase 1 trial in 8 healthy elderly males and females aged 55 to 85 years. While comparing the two delivery methods, this study will also investigate the safety and tolerability of intranasal Rivastigmine.
Trial website
www.clinicalstudies.com.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 53306 0
Dr Bob Soh
Address 53306 0
Nucleus Network Ltd, 5th Floor, Burnet Tower, AMREP Precinct, 89 Commercial Road, Melbourne, Victoria, 3004
Country 53306 0
Australia
Phone 53306 0
+61 3 9076 8900
Fax 53306 0
Email 53306 0
b.soh@nucleusnetwork.com.au
Contact person for public queries
Name 53307 0
Mr Tristan Iseli, PhD
Address 53307 0
Nucleus Network Ltd, 5th Floor, Burnet Tower, AMREP Precinct, 89 Commercial Road, Melbourne, Victoria, 3004
Country 53307 0
Australia
Phone 53307 0
+61 3 9076 8900
Fax 53307 0
Email 53307 0
t.iseli@nucleusnetwork.com.au
Contact person for scientific queries
Name 53308 0
Mr Timothy Morgan, PhD
Address 53308 0
Lachesis Biosciences Pty Ltd, 24 Mickle Crescent, Warrnambool VIC 3280
Country 53308 0
Australia
Phone 53308 0
+61 3 5561 7758
Fax 53308 0
Email 53308 0
tim.morgan@lachesisbio.com.au

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary