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Trial registered on ANZCTR


Registration number
ACTRN12618001817235
Ethics application status
Approved
Date submitted
3/11/2018
Date registered
7/11/2018
Date last updated
16/07/2019
Date data sharing statement initially provided
7/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The extent and rate of atropine sulfate absorption when administered under the tongue in humans
Scientific title
Pharmacokinetics of atropine after sublingual and oral administration in healthy and clozapine-treated adults
Secondary ID [1] 296509 0
None
Universal Trial Number (UTN)
U1111-1223-2206
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypersalivation 310290 0
Drooling 310291 0
Condition category
Condition code
Mental Health 309025 309025 0 0
Schizophrenia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will involve the administration of 0.6mg atropine sulfate solution under the tongue (sublingual) on day 1, 0.6mg atropine sulfate oral (swallowed) tablet at least 4 days after day 1, then 1.2mg atropine sulfate solution under the tongue at least 4 days after day 2.
All participants will have the study medications at this sequence of administration.
The extent and rate of atropine sulfate absorption after sublingual administration will be compared to that after the tablet oral administration.
The study will involve the administration of each dose once only.
Participants will be observed over the first one hour after the medication administration. Participants will be remaining in the Charles Perkins Unit clinics area over the study period (10 hours) on each of the study days.
Intervention code [1] 312824 0
Treatment: Drugs
Comparator / control treatment
The pharmacokinetics of the 0.6mg sublingual dose will be compared to that of the 0.6mg oral tablet and to the 1.2mg atropine sulfate oral tablet
Control group
Active

Outcomes
Primary outcome [1] 307986 0
Time needed for the atropine sulfate to be detected in the venous blood as assessed by serial blood collection.
Timepoint [1] 307986 0
Immediately prior to the administration of the study medication then 5, 10, 20, 30, 40, and 60 minutes and at 2, 3, 6, 8, 9, 10 hours post administration
Secondary outcome [1] 353572 0
Pulse rate as assessed by sphygnamometer
Timepoint [1] 353572 0
The pulse rate will be checked at baselines and then every 15 minutes over the first one hour then every 30 minutes over following one hour after the administration of the study medication.
Secondary outcome [2] 353573 0
Amount of saliva secreted over 5 minutes. Cotton rolls and saliva pads will be used to measure the saliva amount secreted.
Timepoint [2] 353573 0
Saliva secretion will be measured at baselines and 2 hours after the administration of the study medication

Eligibility
Key inclusion criteria
Healthy Participants:
1. Age: between 18 and 50 year old
2. Non pregnant or breast feeding
3. Able to consent for participation in the study
4. Healthy as per the pathology test results, ECG, and medical history.

Clozapine-treated patients:
1. Age: between 18 and 50 year old
2. Non pregnant or breast feeding
3. Able to consent for participation in the study
4. Treated with clozapine.


Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Healthy Participants:
1. Known allergy to atropine
2. Over the last 3 months found to have a serum bilirubin, albumin, or INR outside the normal range.
3. Over the last 3 months found to have an eGFR less than 90mL/min/1.73m2
4. Known to have or found upon screening to have high blood pressure ( more than 140/90), postural hypotension, angina, or cardiac arrhythmia.
5. Known to have glaucoma, myasthenia gravis, prostatic hypertrophy, bladder obstruction, GI obstructive disease such as ileus, or other medical illness that may be seriously adversely affected by atropine, tachycardia secondary to cardiac insufficiency or thyrotoxicosis, fever, or pregnancy induced hypertension.
6. Have dry mouth, hypersalivation or drooling.
7. Treated with an anticoagulants, antiarrhythmics, depolarising and non-depolarising muscle relaxants, or neuromuscular blocking agents.
8. Treated with a medication that has an anticholinergic effects such as: olanzapine, quetiapine, chlorpromazine, hyoscine, benztropine, ipratropium bromide, oxybutynin, solifenacin, darifenacin, sedating antihistamines such as promethazine, benzhexol, tricyclic or tetracyclic antidepressants. Inhalation medications with anticholinergic effect are exempted.
9. Treated with a medication with a cholinergic effect such as Anticholinesterases used in the treatment of dementia such as donepezil.


Clozapine treated participants:

Known to have any of the following conditions:
1. Known allergy to atropine
2. Females during the menstrual period
3. Over the last 3 months found to have a serum bilirubin, albumin, or INR outside the normal range.
4. Over the last 3 months found to have an eGFR less than 90mL/min/1.73m2
5. Known to have or found upon screening to have high blood pressure (more than 140/90), postural hypotension, angina, or cardiac arrhythmia.
6. Known to have glaucoma, myasthenia gravis, prostatic hypertrophy, bladder obstruction, GI obstructive disease such as ileus, or other medical illness that may be seriously adversely affected by atropine, tachycardia secondary to cardiac insufficiency or thyrotoxicosis, fever, or pregnancy induced hypertension.
7. Have severe constipation or diarrhoea.
8. Have dry mouth, hypersalivation or drooling.
9. Wearing dental braces
10. Treated with an anticoagulants, antiarrhythmics, depolarising and non-depolarising muscle relaxants, or neuromuscular blocking agents.
11. Is treated with any medication other than clozapine that is known to have a significant anticholinergic effects such as: olanzapine, quetiapine, chlorpromazine, hyoscine, benztropine, ipratropium bromide, oxybutynin, solifenacin, darifenacin, sedating antihistamines such as promethazine, benzhexol, tricyclic or tetracyclic antidepressants. Inhalation medications with anticholinergic effect are exempted.
12. Treated with a medication with a cholinergic effect such as Anticholinesterases used in the treatment of dementia such as donepezil.

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)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
The 1.2mg sublingual atropine dose will be on the third study day for all participants
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
NSW
Recruitment hospital [1] 12355 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 12356 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 24596 0
2050 - Camperdown
Recruitment postcode(s) [2] 24597 0
2139 - Concord

Funding & Sponsors
Funding source category [1] 301097 0
Government body
Name [1] 301097 0
Sydney Local Health District
Address [1] 301097 0
Level 11 KGV Building, Missenden Rd, Camperdown, NSW 2050
Country [1] 301097 0
Australia
Primary sponsor type
Government body
Name
Sydney Local Health District
Address
Level 11 KGV Building, Missenden Rd, Camperdown, NSW 2050
Country
Australia
Secondary sponsor category [1] 300707 0
Individual
Name [1] 300707 0
Professor Tim Lambert
Address [1] 300707 0
Concord Repatriation and General Hospital, Hospital Rd, Concord West, NSW 2139
Country [1] 300707 0
Australia
Secondary sponsor category [2] 300717 0
University
Name [2] 300717 0
The University of Sydney
Address [2] 300717 0
Level 6, Janes Foss Russell Building, Darlington NSW 2006
Country [2] 300717 0
Australia
Secondary sponsor category [3] 300726 0
Individual
Name [3] 300726 0
Omar Mubaslat
Address [3] 300726 0
Department of Pharmacy, Royal Prince Alfred Hospital. Missenden Rd, NSW 2050
Country [3] 300726 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301846 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 301846 0
Research Ethics and Governance Office (REGO), Royal Prince Alfred Hospital, Missenden Road, CAMPERDOWN NSW 2050
Ethics committee country [1] 301846 0
Australia
Date submitted for ethics approval [1] 301846 0
09/11/2018
Approval date [1] 301846 0
01/02/2019
Ethics approval number [1] 301846 0
HREC/18/RPAH/687

Summary
Brief summary
Atropine sulfate 1% is commonly prescribed to treat excess saliva secretion and drooling in patients treated with clozapine. Clozapine is used for the treatment of schizophrenia.
In this study we aim to measure the amount of atropine that is absorbed when the atropine is administered under the tongue
We will be enrolling healthy adults and clozapine treated adults so we can compare the absorption between the two types of people.
We will also compare the amount of atropine absorbed after under the tongue administration to that after oral (swallowing) administration
The effect of atropine on pulse rate and saliva secretion will be monitored and compared between the sublingual and oral administration.
Trial website
Trial related presentations / publications
Public notes
Serial blood samples collection will be performed are Charles Perkins Center for healthy participants and clozapine treated participants who are residing in the community. One participant will be studied on any one day.

Contacts
Principal investigator
Name 88310 0
Mr Omar Mubaslat
Address 88310 0
The Department of Pharmacy, Royal Prince Alfred Hospital, Missenden Rd, 2050 NSW, Australia
Country 88310 0
Australia
Phone 88310 0
+61 2 9515 8145
Fax 88310 0
+61 2 9515 8400
Email 88310 0
Omar.Mubaslat@health.nsw.gov.au
Contact person for public queries
Name 88311 0
Mr Omar Mubaslat
Address 88311 0
The Department of Pharmacy, Royal Prince Alfred Hospital, Missenden Rd, 2050 NSW, Australia
Country 88311 0
Australia
Phone 88311 0
+61 2 9515 8145
Fax 88311 0
+61 2 9515 8400
Email 88311 0
Omar.Mubaslat@health.nsw.gov.au
Contact person for scientific queries
Name 88312 0
Mr Omar Mubaslat
Address 88312 0
The Department of Pharmacy, Royal Prince Alfred Hospital, Missenden Rd, 2050 NSW, Australia
Country 88312 0
Australia
Phone 88312 0
+61 2 9515 8145
Fax 88312 0
+61 2 9515 8400
Email 88312 0
Omar.Mubaslat@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No benefit from sharing data is anticipated
What supporting documents are/will be available?
No other documents available
Summary results
No Results