Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000662965
Ethics application status
Approved
Date submitted
11/05/2020
Date registered
9/06/2020
Date last updated
8/10/2021
Date data sharing statement initially provided
9/06/2020
Date results information initially provided
8/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Drug therapy to treat sleep apnoea trial
Scientific title
Reboxetine and combination therapy with AD128 in sleep apnoea trial: A double-blind, 3-way cross-over study
Secondary ID [1] 294191 0
Nil
Universal Trial Number (UTN)
Trial acronym
ReboxOSA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive sleep apnoea 306823 0
Condition category
Condition code
Respiratory 305931 305931 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised, placebo-controlled, 3-arm, cross-over study (~1 week wash-out between visits):
Arm 1: single dose of reboxetine (4mg) (oral capsule) immediately prior to sleep (single overnight, in-laboratory study)
Arm 2: single dose of combination therapy with AD128 (4mg for agent #1 and +5mg for agent #2) (oral capsule) immediately prior to sleep (single overnight, in-laboratory study)
Arm 3: placebo (oral capsule) immediately prior to sleep (single overnight, in-laboratory 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] 300483 0
Treatment: Drugs
Comparator / control treatment
Placebo (StarCap 1500, Maize Starch) vs. reboxetine and
placebo (StarCap 1500, Maize Starch) vs. AD128
Control group
Active

Outcomes
Primary outcome [1] 304963 0
Sleep apnoea severity using the apnoea/hypopnoea index from the overnight polysomnogram
Timepoint [1] 304963 0
Single acute overnight sleep studies (placebo vs. drug nights, approximately 1 week wash out between studies)
Secondary outcome [1] 343751 0
Sleep efficiency from the overnight polysomnogram
Timepoint [1] 343751 0
Single acute overnight sleep studies (placebo vs. drug nights, approximately 1 week wash out between studies)
Secondary outcome [2] 343752 0
Karolinska Sleepiness Scale (KSS) questionnaire measured after awakening after each sleep study
Timepoint [2] 343752 0
After each overnight sleep study (placebo vs. drug nights, approximately 1 week wash out between studies)
Secondary outcome [3] 343754 0
Hypoxemia from the overnight polysomnogram measured using pulse oximetry
Timepoint [3] 343754 0
Single acute overnight sleep studies (placebo vs. drug nights, approximately 1 week wash out between studies)
Secondary outcome [4] 343755 0
Alertness measured after awakening after each sleep study using the AusEd driving simulator
Timepoint [4] 343755 0
After each overnight sleep study (placebo vs. drug nights, approximately 1 week wash out between studies)
Secondary outcome [5] 382559 0
arousal index (number of events/h sleep) measured via polysomnography during each overnight sleep study
Timepoint [5] 382559 0
Single acute overnight sleep studies (placebo vs. drug nights, approximately 1 week wash out between studies)

Eligibility
Key inclusion criteria
Otherwise healthy men and women with obstructive sleep apnoea aged 18-65 years
BMI between 18.5 and 40.0 kg/m2, inclusive, at visit 1.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study.
Medical Conditions
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 poorly controlled hypertension.
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. Narrow angle glaucoma.
13. Women who are pregnant or nursing.
14. Allergy to the study medications
15. Any medication known to influence breathing, sleep/arousal or muscle physiology.
16. Claustrophobia.
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.
Prior/Concurrent Clinical Study Experience
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)
Central randomisation by study pharmacist
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
10/06/2020
Actual
9/06/2020
Date of last participant enrolment
Anticipated
18/05/2021
Actual
16/11/2020
Date of last data collection
Anticipated
1/06/2021
Actual
3/12/2020
Sample size
Target
15
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment postcode(s) [1] 30190 0
5042 - Flinders University
Recruitment postcode(s) [2] 30191 0
2037 - Glebe

Funding & Sponsors
Funding source category [1] 298822 0
Commercial sector/Industry
Name [1] 298822 0
Apnimed Australia Pty Ltd.
Country [1] 298822 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Sturt Rd, Bedford Park SA 5042
Country
Australia
Secondary sponsor category [1] 306033 0
None
Name [1] 306033 0
Address [1] 306033 0
Country [1] 306033 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299771 0
Bellberry Limited
Ethics committee address [1] 299771 0
123 Glen Osmond Rd, Eastwood SA 5063
Ethics committee country [1] 299771 0
Australia
Date submitted for ethics approval [1] 299771 0
Approval date [1] 299771 0
21/05/2020
Ethics approval number [1] 299771 0
2019-12-1081

Summary
Brief summary
The aims of this study are to determine the effects of the medication reboxetine and combination therapy (AD128) on OSA severity (as measured by the apnoea/hypopnoea index during overnight polysomnography) versus placebo. We will also examine other key sleep parameters and the effects on next day sleepiness and alertness.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81514 0
Prof Danny Eckert
Address 81514 0
Adelaide Institute for Sleep Health, Flinders University,
Level 2, Mark Oliphant Building
5 Laffer Drive, Bedford Park SA 5042
Country 81514 0
Australia
Phone 81514 0
+61874219780
Fax 81514 0
Email 81514 0
[email protected]
Contact person for public queries
Name 81515 0
Ms Carolin Tran
Address 81515 0
Adelaide Institute for Sleep Health, Flinders University,
Level 2, Mark Oliphant Building
5 Laffer Drive, Bedford Park SA 5042
Country 81515 0
Australia
Phone 81515 0
+6187421 9873
Fax 81515 0
Email 81515 0
[email protected]
Contact person for scientific queries
Name 81516 0
Prof Danny Eckert
Address 81516 0
Adelaide Institute for Sleep Health, Flinders University,
Level 2, Mark Oliphant Building
5 Laffer Drive, Bedford Park SA 5042
Country 81516 0
Australia
Phone 81516 0
+61874219780
Fax 81516 0
Email 81516 0
[email protected]

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?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo A single 4mg dose of reboxetine modestly reduces o... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseThe norepinephrine reuptake inhibitor reboxetine alone reduces obstructive sleep apnea severity: a double-blind, placebo-controlled, randomized crossover trial.2023https://dx.doi.org/10.5664/jcsm.10256
N.B. These documents automatically identified may not have been verified by the study sponsor.