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Trial registered on ANZCTR


Registration number
ACTRN12619000697189
Ethics application status
Approved
Date submitted
1/05/2019
Date registered
9/05/2019
Date last updated
22/06/2020
Date data sharing statement initially provided
9/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Oral Pilocarpine tablets for advanced cancer patients with dry mouth.
Scientific title
Oral Pilocarpine tablets for Xerostomia in patients with advanced cancer – an N-of-1 feasibility pilot study
Secondary ID [1] 297961 0
None
Universal Trial Number (UTN)
None
Trial acronym
OPX
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
xerostomia 312358 0
Condition category
Condition code
Cancer 310915 310915 0 0
Any cancer
Oral and Gastrointestinal 311176 311176 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment group: Pilocarpine 5mg Oral Dissolvable Tablets; one tablet orally, three times per day (5 mg per dose) 60 minutes before each main meal (breakfast, lunch, dinner) for 3 days. Placebo Oral Dissolvable Tablets; one tablet orally, three times per day -60 minutes before each main meal (breakfast, lunch, dinner) for 3 days. This is 1 cycle, with 3 cycles in total - in random order.
The washout period is 24hrs. Day 2 and 3 data are included in the analysis.
Tablets are returned at the end of the trial to study staff.
The participant diary documents daily doses taken/not taken.
Third daily phone calls monitor compliance with medication.


Intervention code [1] 314180 0
Treatment: Drugs
Comparator / control treatment
Control group: Placebo (matching Oral Dissolvable Tablets). Identical dosing schedule to treatment.
Placebo made from flavour powder, bitterness reducing agent, stevia powder, Medi-RDT Base.
Control group
Placebo

Outcomes
Primary outcome [1] 319739 0
Number of participants recruited over the study period who complete all trial requirements.
Master Log of participants whom reach Day 18 of the trial, and complete the daily Participant Diary which includes:
Numerical Rating Scale and Xerostomia Inventory
Oral Health Impact Profile
Patient Global Impact of Change
common side effects
medication compliance
changes in conmeds
preferred medicine after each cycle

Timepoint [1] 319739 0
Day 18
Secondary outcome [1] 369347 0
Mean NRS score for average dry mouth
Timepoint [1] 369347 0
over the previous 24 hours on days 2 and 3 of each cycle pair
A cycle pair is 3 days of active drug and 3 days of placebo (Random order).
Secondary outcome [2] 369348 0
Number of participants in whom a decision can be made regarding the benefit or otherwise of ODT versus placebo using N-of-1 methodology.
Participant diary questionnaires:
Numerical Rating Scale and Xerostomia Inventory
Oral Health Impact Profile
Patient Global Impact of Change
Timepoint [2] 369348 0
Day 18
Secondary outcome [3] 369351 0
Adverse Events - National Cancer Institute, Common Terminology Criteria for Adverse Events. V4.0 (2010)
- increased sweating
- headache
- nausea/vomiting
- dizziness
- muscle tremors
- breathing difficulties
- abdominal discomfort
- dysgeusia
- excess saliva
Timepoint [3] 369351 0
every third day of each 6-day cycle for 18 days
Secondary outcome [4] 369352 0
Patients Global Impression of change (PGIC)
Timepoint [4] 369352 0
every third day of each 6-day cycle
Secondary outcome [5] 369353 0
NRS for dysphagia
Timepoint [5] 369353 0
daily for 18 days
Secondary outcome [6] 369354 0
Xerostomia Inventory scores (XI)
Timepoint [6] 369354 0
every third day of each 6-day cycle
Secondary outcome [7] 369355 0
Oral Health Impact Profile (OHIP)
Timepoint [7] 369355 0
every third day of each 6-day cycle
Secondary outcome [8] 369960 0
NRS for dysgeusia
Timepoint [8] 369960 0
daily for 18 days

Eligibility
Key inclusion criteria
1. Patients aged >=18 years with malignant disease;
2. a clinical diagnosis of chronic dry mouth that has been present for at least 2 weeks with no likelihood of resolution during the trial period
3. a numerical rating scale (NRS) score of >=3 on a 10-point xerostomia scale;
4. liver function (AST, ALT) <5x upper limit of normal, and total bilirubin within normal range within the week prior to trial registration;
5. no known allergy or sensitivity to pilocarpine;
6. ability to give fully informed written consent and complete all trial requirements.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. no plan to change any medication with the potential to cause dry mouth within the trial period. Patients already on pilocarpine are eligible but must stop these drugs 1 week before trial commencement.
2. no intervention e.g. radiotherapy, chemotherapy, surgery that might alter dry mouth symptoms during the 2 weeks prior to the study period or plans to undergo such therapy during the study period
3. ocular problems contraindicating the use of parasympathetic agents (eg irido-cyclitis, increased intra-ocular pressure);
4. other comorbidity where there is a risk of worsening co-existing medical problems during the trial period and/or active treatment is contemplated eg severe or uncontrolled asthma or pulmonary disease, uncontrolled hypo-or hypertension, hyperthyroidism, uncontrolled seizures or cardiac arrythmias, (especially bradycardias) and Parkinson's disease;
5. a poor understanding of written or spoken English that would preclude completion of all trial requirements
6. an active oral infection i.e. candidiasis, herpetic infections, mucositis, mouth ulcers

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)
Schedule kept by central pharmacy to allocate and dispense.
Drug concealed by numbering system - bottles 1-6.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N-of-1 design sequence generated by computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
single patient multiple crossover studies
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Based on prior clinical trial experience, 15 participants will give an adequate sample size to define the feasibility, and determine if this method could be used as the basis for future multi-centre studies with the ability to recruit adequate numbers of participants to answer clinically important research questions. Descriptive statistics will be provided for demographic and secondary outcome measures including safety data. Individual and population treatment differences will be calculated using hierarchical Bayesian methods and employ non-informative priors in the first instance – following the method of Zucker et al (1997) for normally distributed data and Schluter and Ware (2005) for binary data.

Recruitment
Recruitment status
Not yet 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)
QLD
Recruitment hospital [1] 13658 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [2] 13659 0
Mater Private Hospital - South Brisbane
Recruitment postcode(s) [1] 26341 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 302480 0
Hospital
Name [1] 302480 0
Mater Misericordiae Ltd
Address [1] 302480 0
Raymond Tce
South Brisbane, Qld, 4101
Country [1] 302480 0
Australia
Primary sponsor type
Hospital
Name
Mater Misericordiae Ltd
Address
Raymond Tce
South Brisbane, Qld, 4101
Country
Australia
Secondary sponsor category [1] 302505 0
None
Name [1] 302505 0
Address [1] 302505 0
Country [1] 302505 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303142 0
Mater Misericordiae Ltd Human Research Ethics Committee
Ethics committee address [1] 303142 0
Raymond Tce
South Brisbane, Qld 4101
Ethics committee country [1] 303142 0
Australia
Date submitted for ethics approval [1] 303142 0
Approval date [1] 303142 0
15/04/2019
Ethics approval number [1] 303142 0
HREC/MML/49208

Summary
Brief summary
This study will evaluate the feasibility and efficacy of pilocarpine on xerostomia for patients with cancer

Who is it for?
You may be eligible to join this study if you are aged 18 and above, have been diagnosed with cancer and xerostomia

Study details
Participants in this study will receive both the interventional drug and placebo drug but in a random sequence. At the beginning of the study, Participants will receive 6 bottles of drug. 3 bottles contain placebo and 3 contain the drug pilocarpine. The 6 bottles will be taken randomly as instructed by the pharmacy over 18 days. Participants will not know which bottle has what drug. The drug will be taken three times a day for the 18 day trial.
All participants will complete a diary which will provide information around dry mouth symptoms, and document any adverse events/side effects experienced.

We hope that this drug and formulation will be able to help cancer patients in the future who suffer from the debilitating symptom of chronic dry mouth.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92618 0
Dr Evan Richard
Address 92618 0
Mater Misericordiae Ltd, Raymond Tce, South Brisbane, Qld, 4101.
Country 92618 0
Australia
Phone 92618 0
+61 7 3163 8111
Fax 92618 0
Email 92618 0
evan.richard@mater.org.au
Contact person for public queries
Name 92619 0
Mrs Karyn Foster
Address 92619 0
Mater Misericordiae Ltd, Raymond Tce, South Brisbane, Qld, 4101.
Country 92619 0
Australia
Phone 92619 0
+61 7 3163 3884
Fax 92619 0
Email 92619 0
karyn.foster@mater.org.au
Contact person for scientific queries
Name 92620 0
Prof Janet Hardy
Address 92620 0
Mater Misericordiae Ltd, Raymond Tce, South Brisbane, Qld, 4101.
Country 92620 0
Australia
Phone 92620 0
+61 7 3163 8111
Fax 92620 0
Email 92620 0
janet.hardy@mater.org.au

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