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Trial registered on ANZCTR


Registration number
ACTRN12613000892718
Ethics application status
Approved
Date submitted
7/08/2013
Date registered
9/08/2013
Date last updated
16/01/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised, Placebo-Controlled, Double-Blind, Single Dose Escalation Study to evaluate the Safety, Tolerability and Pharmacokinetics of Betahistine Dihydrochloride Following a Single Intranasal Dose in Healthy Male and Female Volunteers.
Scientific title
A Randomised, Placebo-Controlled, Double-Blind, Single Dose Escalation Study to evaluate the Safety, Tolerability and Pharmacokinetics of Betahistine Dihydrochloride Following a Single Intranasal Dose in Healthy Male and Female Volunteers.
Secondary ID [1] 282968 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
OME (Otitis Media with Effusion) 289789 0
Condition category
Condition code
Ear 290143 290143 0 0
Other ear disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single ascending dose of a betahistine dihydrochloride or placebo administered intranasally in healthy male and female volunteers. The dose levels planned for this study are 10, 20 and 40 mg in 3 cohorts. 8 participants in each cohort will be dosed with either the test medication or placebo in a double-blind manner. The duration of each cohort is 7 days post dose.
Intervention code [1] 287680 0
Treatment: Drugs
Comparator / control treatment
The vehicle will be used as the matched placebo formulation. Both the test drug and placebo are administered intranasally.
Control group
Placebo

Outcomes
Primary outcome [1] 290176 0
Safety and tolerability of a single intranasal dose of betahistine dihydrochloride (BH) of 10, 20 or 40 mg in healthy male and female volunteers will be assessed on the basis of adverse events reported, blood pressure, heart rate, body temperature (oral), electrocardiograms (ECGs), clinical laboratory tests, physical examination and tympanometry. The methods used will be medical equipment and questioning. No specific adverse events are expected.
Timepoint [1] 290176 0
Subjects will be continuously monitored for adverse events, blood pressure, heart rate, body temperature, electrocardiograms (ECGs), clinical laboratory tests, physical examination and tympanometry whist on study (from predose to Day 7).
Primary outcome [2] 290194 0
To characterise the single dose pharmacokinetics of betahistine dihydrochloride at 10mg, 20mg, 40mg in healthy male and female volunteers.

Plasma samples derived from venous blood will be analysed using a validated liquid chromatographic (LC) tandem mass spectrometric detection (MS/MS) achiral method to determine the concentrations of betahistine dihydrochloride and its major metabolite, 2-pyridylacetic acid, at a range of timepoints. This information will then be used to determine single dose pharmacokinetic parameters including Cmax, Tmax, AUC and T(half).
Timepoint [2] 290194 0
The pharmacokinetics of betahistine dihydrochloride will be collected at predetermined timepoints through the study and measured after each cohort. These time points are: predose, 2, 5, 10, 15, 20, 30, 60, 90 minutes and 2, 6, and 12 hours, 24 hours postdose, Day 4 and Day 7.
Secondary outcome [1] 304057 0
To explore the pharmacodynamic effect of BH on Eustachian tube function using tympanometry testing.
Timepoint [1] 304057 0
Predose, then at 10 minutes, 2 hours and 6 hours, 24 hours postdose.

Eligibility
Key inclusion criteria
Healthy male and female volunteers having Body Mass Index (MBI) between 18 and 30kg/m2 inclusive.
Normal (Type A) tympanometric measurements at screening consistent with the normal healthy adult population.
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
History or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, haematological, neurologic, psychiatric, systemic, ocular, or infectious disease; any acute infectious disease or signs of acute illness, especially of the ear, nose or throat (ENT).
History of recurrent ENT infections, irritation or localized reaction to intranasally applied agents.
Recent ENT surgery (within 3 months of screening).

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
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)
WA,VIC
Recruitment hospital [1] 1390 0
The Alfred - Prahran
Recruitment hospital [2] 3336 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 7255 0
3004 - Melbourne
Recruitment postcode(s) [2] 9124 0
6009 - Broadway Nedlands

Funding & Sponsors
Funding source category [1] 287742 0
Commercial sector/Industry
Name [1] 287742 0
Otifex Therapeutics Pty Ltd
Address [1] 287742 0
Level 9, 278 Collins Street,
Melbourne VIC 3000
Country [1] 287742 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Otifex Therapeutics Pty Ltd
Address
Level 9, 278 Collins Street,
Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 286468 0
None
Name [1] 286468 0
Address [1] 286468 0
Country [1] 286468 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289695 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 289695 0
The Alfred Hospital
55 Commercial Rd Melbourne VIC 3004
Ethics committee country [1] 289695 0
Australia
Date submitted for ethics approval [1] 289695 0
17/07/2013
Approval date [1] 289695 0
01/08/2013
Ethics approval number [1] 289695 0
259/13
Ethics committee name [2] 292219 0
Bellberry Limited
Ethics committee address [2] 292219 0
129 Glen Osmond Rd
Eastwood SA 5063
Ethics committee country [2] 292219 0
Australia
Date submitted for ethics approval [2] 292219 0
20/11/2013
Approval date [2] 292219 0
18/12/2013
Ethics approval number [2] 292219 0
2013-11-625

Summary
Brief summary
Betahistine dihydrochloride administered off-label intranasally is an experimental drug being investigated for its potential as a treatment for otitis media with effusion for this clinical trial. lt is hoped that this information will lead to improved clinical management of this condition.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41998 0
Dr Janakan Krishnarajah
Address 41998 0
Medical Director & CEO
Linear Clinical Research Ltd
QEII Medical Centre, 1st Floor, B Block, Hospital Avenue
Nedlands WA 6009
Country 41998 0
Australia
Phone 41998 0
+61 8 6382 5100
Fax 41998 0
+61 8 9381 4453
Email 41998 0
jkrishnarajah@linear.org.au
Contact person for public queries
Name 41999 0
Dr Janakan Krishnarajah
Address 41999 0
Medical Director & CEO
Linear Clinical Research Ltd
QEII Medical Centre, 1st Floor, B Block, Hospital Avenue
Nedlands WA 6009
Country 41999 0
Australia
Phone 41999 0
+61 8 6382 5100
Fax 41999 0
+61 8 9381 4453
Email 41999 0
jkrishnarajah@linear.org.au
Contact person for scientific queries
Name 42000 0
Dr Christopher Wraight
Address 42000 0
Otifex Therapeutics Pty Ltd
Level 9, 278 Collins Street
Melbourne VIC 3000
Country 42000 0
Australia
Phone 42000 0
+61 3 9657 0700
Fax 42000 0
Email 42000 0
cwraight@otifex.com

No information has been provided regarding IPD availability
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