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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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Alzheimer's disease

Condition category

Condition code

Neurological

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]

Treatment: Drugs

Intervention code [2]

Treatment: Devices

Comparator / control treatment

Arm 1: Intravenous Rivastigmine 1mg

Control group

Active

Outcomes

Primary outcome [1]

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]

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]

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]

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

Sex

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

1/02/2015

Actual

10/03/2015

Date of last participant enrolment

Anticipated

Actual

20/03/2015

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Alfred - Prahran

Recruitment postcode(s) [1]

3004 - Melbourne

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Lachesis Biosciences Pty Ltd

Address [1]

24 Mickle Crescent, Warrnambool VIC 3280

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Alfred Health Human Ethics Committee

Ethics committee address [1]

The Alfred Hospital, Commercial Road, Melbourne, Victoria, 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

26/11/2014

Approval date [1]

19/12/2014

Ethics approval number [1]

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

Dr Bob Soh

Address

Nucleus Network Ltd, 5th Floor, Burnet Tower, AMREP Precinct, 89 Commercial Road, Melbourne, Victoria, 3004

Country

Australia

Phone

+61 3 9076 8900

Fax

b.soh@nucleusnetwork.com.au

Contact person for public queries

Name

Tristan Iseli, PhD

Address

Nucleus Network Ltd, 5th Floor, Burnet Tower, AMREP Precinct, 89 Commercial Road, Melbourne, Victoria, 3004

Country

Australia

Phone

+61 3 9076 8900

Fax

t.iseli@nucleusnetwork.com.au

Contact person for scientific queries

Name

Timothy Morgan, PhD

Address

Lachesis Biosciences Pty Ltd, 24 Mickle Crescent, Warrnambool VIC 3280

Country

Australia

Phone

+61 3 5561 7758

Fax

tim.morgan@lachesisbio.com.au

No information has been provided regarding IPD availability

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

Source	Title	Year of Publication	DOI
Dimensions AI	Intranasal Drug Administration in Alzheimer-Type Dementia: Towards Clinical Applications	2023	https://doi.org/10.3390/pharmaceutics15051399

N.B. These documents automatically identified may not have been verified by the study sponsor.

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