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Trial registered on ANZCTR


Registration number
ACTRN12618001499279
Ethics application status
Approved
Date submitted
3/09/2018
Date registered
6/09/2018
Date last updated
30/09/2019
Date data sharing statement initially provided
21/01/2019
Date results information initially provided
30/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of AD098, AD153 and AD639 on obstructive sleep apnoea (OSA)
Scientific title
The effects of AD098, AD153 and AD639 on obstructive sleep apnoea (OSA) severity in men and women with moderate-to-severe OSA
Secondary ID [1] 294651 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive Sleep Apnoea 307493 0
Condition category
Condition code
Respiratory 306578 306578 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: AD098 - (single dose [one night], combination of drugs [60mg+5mg], oral capsule, administered prior to sleep)
Arm 2: AD153 - (single dose [one night], combination of drugs [50mg+5mg], oral capsule, administered prior to sleep)
Arm 3: AD639 - (single dose [one night], single drug [5mg], oral capsule, administered prior to sleep)
Approximately 1-week washout between each arm

To ensure adherence, all drugs are to be administered by research staff during the in-laboratory sleep studies (polysomnography) performed at the Monash University Sleep Research Facility.
Intervention code [1] 300948 0
Treatment: Drugs
Comparator / control treatment
Placebo (cellulose capsule) taken orally prior to sleep (participants will act as their own controls in a cross-over design)
Control group
Placebo

Outcomes
Primary outcome [1] 305574 0
Sleep apnoea severity using the apnoea/hypopnoea index from the overnight polysomnogram
Timepoint [1] 305574 0
Single acute overnight sleep studies (placebo vs. drug)
Secondary outcome [1] 345808 0
Subjective sleepiness measured with the Stanford Sleepiness Scale
Timepoint [1] 345808 0
Single acute overnight sleep studies (placebo vs. drug). 30 mins post-awakening from overnight sleep study
Secondary outcome [2] 345809 0
Subjective sleep quality will be assessed by asking participants to assign a rating score indicating how they felt they slept during the night of the overnight polysomnogram study (worst:0, best:10)
Timepoint [2] 345809 0
Single acute overnight sleep studies (placebo vs. drug). 30 mins post-awakening from overnight sleep study
Secondary outcome [3] 351300 0
Blood pressure (diastolic and systolic) measured with an automatic sphygmomanometer
Timepoint [3] 351300 0
Single acute overnight sleep studies (placebo vs. drug). Measured 10 minutes before 'lights out' of each overnight sleep study period; and then again at 10 minutes post-awakening in the morning after each night study.
Secondary outcome [4] 351301 0
Heart rate measured with an automatic sphygmomanometer
Timepoint [4] 351301 0
Single acute overnight sleep studies (placebo vs. drug). Measured 10 minutes before 'lights out' of each overnight sleep study period; and then again at 10 minutes post-awakening in the morning after each night study.
Secondary outcome [5] 351302 0
Sleep efficiency from the overnight polysomnogram
Timepoint [5] 351302 0
Single acute overnight sleep studies (placebo vs. drug)
Secondary outcome [6] 351485 0
Hypoxemia from the overnight polysomnogram measured using oximetry
Timepoint [6] 351485 0
Single acute overnight sleep studies (placebo vs. drug)
Secondary outcome [7] 351486 0
Arousal index from the overnight polysomnogram
Timepoint [7] 351486 0
Single acute overnight sleep studies (placebo vs. drug)

Eligibility
Key inclusion criteria
Otherwise healthy men and women with moderate-to-severe obstructive sleep apnoea
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
•Any chronic medical condition other than controlled hypertension, hyperlipidemia, diabetes.
•Any medication known to influence breathing, sleep/arousal or muscle physiology.
•Claustrophobia.
•Inability to sleep supine.
•BMI>45
•Central apnea index >5 events/h
•Tonsillar hypertrophy or craniofacial malformation
•Allergy to lidocaine, oxymetazoline HCl or study medications
•For women: Pregnancy or breast feeding.

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created 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
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Outcomes will be assessed by linear mixed-effect modelling using treatment condition as a fixed effect. Based on a previous pilot study, a sample size of 10 will allow us to detect a difference of 18 (± 18) events/h with 80% power and a 5% level of significance

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

Funding & Sponsors
Funding source category [1] 299265 0
Commercial sector/Industry
Name [1] 299265 0
Apnimed
Address [1] 299265 0
Apnimed, Inc.
19 Ware St. Apt. 3
Cambridge, MA 02138
USA
Country [1] 299265 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Apnimed
Address
Apnimed, Inc.
19 Ware St. Apt. 3
Cambridge, MA 02138
USA
Country
United States of America
Secondary sponsor category [1] 300001 0
None
Name [1] 300001 0
Address [1] 300001 0
Country [1] 300001 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300180 0
Monash University Human Research Ethics Committee
Ethics committee address [1] 300180 0
Monash University Human Research Ethics Committee (MUHREC)
Room 111, Chancellery Building D,
26 Sports Walk, Clayton Campus
Research Office
Monash University VIC 3800
Ethics committee country [1] 300180 0
Australia
Date submitted for ethics approval [1] 300180 0
03/09/2018
Approval date [1] 300180 0
15/10/2018
Ethics approval number [1] 300180 0
ID:16795

Summary
Brief summary
The primary aim of this study is to assess the effect that three combinations of drugs (known as AD098, AD153, AD639) have on sleep apnoea severity (i.e. apnoea/hypopnoea index) compared to placebo. Additional measures of sleep apnoea severity, cardiovascular and sleepiness outcomes will also be assessed as secondary outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82814 0
Dr Bradley Edwards
Address 82814 0
Department of Physiology and School of Psychological Sciences
Faculty of Medicine, Nursing and Health Sciences, Monash University
264 Ferntree Gully Road, Notting Hill,
VIC 3168
Country 82814 0
Australia
Phone 82814 0
+613 9905 0187
Fax 82814 0
Email 82814 0
bradley.edwards@monash.edu
Contact person for public queries
Name 82815 0
Dr Bradley Edwards
Address 82815 0
Department of Physiology and School of Psychological Sciences
Faculty of Medicine, Nursing and Health Sciences, Monash University
264 Ferntree Gully Road, Notting Hill,
VIC 3168
Country 82815 0
Australia
Phone 82815 0
+613 9905 0187
Fax 82815 0
Email 82815 0
bradley.edwards@monash.edu
Contact person for scientific queries
Name 82816 0
Dr Bradley Edwards
Address 82816 0
Department of Physiology and School of Psychological Sciences
Faculty of Medicine, Nursing and Health Sciences, Monash University
264 Ferntree Gully Road, Notting Hill,
VIC 3168
Country 82816 0
Australia
Phone 82816 0
+613 9905 0187
Fax 82816 0
Email 82816 0
bradley.edwards@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This will only be done if participant identity can be assured to remain anonymous in accordance with ethical approval.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary