ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12619001427167

Ethics application status

Approved

Date submitted

24/09/2019

Date registered

15/10/2019

Date last updated

27/10/2021

Date data sharing statement initially provided

15/10/2019

Date results provided

27/10/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

The effects of a novel drug combination on sleep quality in people with sleep apnoea.

Scientific title

The effects of combination therapy (AD173) on sleep efficiency and the respiratory arousal threshold in people with sleep apnoea

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Obstructive sleep apnoea

Condition category

Condition code

Respiratory

Sleep apnoea

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Randomised, placebo-controlled, cross-over study (~1 week wash-out between visits):
Arm 1: single dose of AD036 drug combination (2 oral capsules) immediately prior to sleep (single overnight study)
Arm 2: single dose of AD173 drug combination (2 oral capsules) immediately prior to sleep (single overnight study)
Interventions will be administered by a study investigator on each visit just prior to sleep for these acute sleep studies to ensure adherence.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

AD173 vs. AD036 (control arm)

Control group

Active

Outcomes

Primary outcome [1]

Difference in sleep efficiency (% total sleep time) between AD036 vs. AD173 measured via polysomnography during each overnight sleep study

Timepoint [1]

Each overnight sleep study (2 single night sleep studies, one on each arm, approximately 1 week wash out between studies)

Secondary outcome [1]

Difference in respiratory arousal threshold (negative epiglottic pressure in cmH2O just prior to arousal) between AD036 vs. AD173 measured via polysomnography during each overnight sleep study

Timepoint [1]

Each overnight sleep study (2 single night sleep studies, one on each arm, approximately 1 week wash out between studies)

Secondary outcome [2]

Difference in apnoea/hypopnoea index (number of events/h sleep) between AD036 vs. AD173 measured via polysomnography during each overnight sleep study

Timepoint [2]

Each overnight sleep study (2 single night sleep studies, one on each arm, approximately 1 week wash out between studies)

Secondary outcome [3]

Difference in Karolinska Sleepiness Scale (KSS) questionnaire between AD036 vs. AD173 measured after awakening after each sleep study

Timepoint [3]

After each overnight sleep study (2 single night sleep studies, one on each arm, approximately 1 week wash out between studies)

Secondary outcome [4]

Difference in AusEd driving simulator task performance (objective alertness) between AD036 vs. AD173 measured after awakening after each sleep study

Timepoint [4]

After each overnight sleep study (2 single night sleep studies, one on each arm, approximately 1 week wash out between studies)

Secondary outcome [5]

Difference in arousal index (number of events/h sleep) between AD036 vs. AD173 measured via polysomnography during each overnight sleep study

Timepoint [5]

Each overnight sleep study (2 single night sleep studies, one on each arm, approximately 1 week wash out between studies)

Secondary outcome [6]

Difference in nadir oxygen saturation (%) between AD036 vs. AD173 measured via polysomnography during each overnight sleep study

Timepoint [6]

Each overnight sleep study (2 single night sleep studies, one on each arm, approximately 1 week wash out between studies)

Eligibility

Key inclusion criteria

Otherwise healthy men and women with obstructive sleep apnoea
-Adults between 18 to 64 years of age, inclusive
- BMI between 18.5 and 40.0 kg/m2, inclusive

Minimum age

18 Years

Maximum age

64 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. History of narcolepsy.
2. Clinically significant craniofacial malformation.
3. Clinically significant cardiac disease (e.g., rhythm disturbances, coronary artery disease or cardiac failure) or hypertension requiring more than 2 medications for control.
4. Clinically significant neurological disorder, including epilepsy/convulsions.
5. History of schizophrenia, schizoaffective disorder or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM V) or International Classification of Disease tenth edition criteria.
6. History of attempted suicide or suicidal ideation within 1 year prior to screening, or current suicidal ideation.
7. History of clinically significant constipation, gastric retention, or urinary retention, benign prostatic hyperplasia.
8. History of moderate or severe hepatic or renal impairment.
9. History of drug abuse or substance use disorder as defined in DSM-V within 12 months.
10. A significant acute illness or infection requiring medical treatment in the past 30 days.
11. Clinically significant cognitive dysfunction.
12. Untreated narrow angle glaucoma.
13. Women who are pregnant or nursing.
14. Known allergy to any of the study medications.
15. Any medication known to influence breathing, sleep/arousal or muscle physiology.
16. Clausrophobia.
17. Use of medications from the list of disallowed concomitant medications.
18. Treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors, strong cytochrome P450 2D6 (CYP2D6) inhibitors, or monoamine oxidase inhibitors (MAOI) within 14 days of the start of study.
19. Use of another investigational agent within 30 days or 5 half-lives, whichever is longer, prior to dosing.

Other Exclusions
20. <5 hours typical sleep duration.
21. Night- or shift-work sleep schedule.
22. Employment as a commercial driver or operator of heavy or hazardous equipment.
23. Smoking more than 10 cigarettes or 2 cigars per day.
24. Unwilling to use contraception during the study (if relevant).
25. Unwilling to avoid alcohol on the days of the study.
26. Unwilling to limit caffeinated beverage intake (e.g., coffee, cola, tea) to 400 mg/day or less of caffeine, not to be used within 3 hours of bedtime on study days.
27. Any condition that in the investigator’s opinion would present an unreasonable risk to the participant, or which would interfere with their participation in the study or confound study interpretation.
28. Participant considered by the investigator, for any reason, an unsuitable candidate to receive the study medications or unable or unlikely to understand or comply with the study design.

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

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 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

21/10/2019

Actual

6/11/2019

Date of last participant enrolment

Anticipated

Actual

11/06/2020

Date of last data collection

Anticipated

Actual

18/06/2020

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Apnimed Australia Pty Ltd.

Address [1]

58 Gipps Street, Collingwood, Victoria 3066

Country [1]

Australia

Primary sponsor type

University

Name

Flinders University

Address

Sturt Rd, Bedford Park SA 5042

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Adelaide Clinical Research Ethics Committee

Ethics committee address [1]

Office for Research / 
Southern Adelaide Local Health Network
Flinders Medical Centre
Bedford Park SA 5042

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

13/09/2019

Ethics approval number [1]

89.19

Summary

Brief summary

The aim of this study is to determine the effects of the combination therapies (collectively "AD173") on sleep efficiency in patients with OSA. Recently, a combination of medications (AD036) was shown to markedly reduce OSA severity. However, there were signs that sleep quality was reduced (lower arousal threshold). We recently showed that the common sleep promotion aids improve sleep efficiency in OSA and upper airway muscle activity. Thus, the combination of AD173 has the potential to improve sleep efficiency and sleep and breathing variables compared to AD036 alone. Secondary outcomes include the effect of these combined agents on the arousal threshold and other sleep and respiratory parameters. In addition, we will measure sleepiness and next day alertness.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Danny Eckert

Address

Adelaide Institute for Sleep Health, Flinders University,
Level 2, Mark Oliphant Building
5 Laffer Drive, Bedford Park SA 5042

Country

Australia

Phone

+61 8 74219780

Fax

danny.eckert@flinders.edu.au

Contact person for public queries

Name

Carolin Tran

Address

Adelaide Institute for Sleep Health, Flinders University,
Level 2, Mark Oliphant Building
5 Laffer Drive, Bedford Park SA 5042

Country

Australia

Phone

+61 8 7421 9873

Fax

carolin.tran@flinders.edu.au

Contact person for scientific queries

Name

Jayne Carberry

Address

Adelaide Institute for Sleep Health, Flinders University,
Level 2, Mark Oliphant Building
5 Laffer Drive, Bedford Park SA 5042

Country

Australia

Phone

+61 8 82015196

Fax

danny.eckert@flinders.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

De-identified individual participant data for the key study outcomes will be provided in the publication.

When will data be available (start and end dates)?

After the study is complete and the findings are published. No end date.

Available to whom?

Everyone with access to the journal publication.

Available for what types of analyses?

Any purpose.

How or where can data be obtained?

Via the journal publication.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
5021	Ethical approval					378214-(Uploaded-15-11-2019-16-34-04)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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