Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001153101
Ethics application status
Approved
Date submitted
26/07/2019
Date registered
19/08/2019
Date last updated
2/06/2022
Date data sharing statement initially provided
19/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
30 day study of 3 different combinations of a medication (AD-036) versus placebo in people with obstructive sleep apnoea
Scientific title
4-week placebo-controlled outpatient dose finding, efficacy, safety and tolerability study of 3 different fixed dose combinations of AD-036 versus placebo in obstructive sleep apnoea
Secondary ID [1] 298659 0
Nil
Universal Trial Number (UTN)
Trial acronym
APN-004
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive sleep apnoea 313787 0
Condition category
Condition code
Respiratory 312193 312193 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
4 Arms:
Group 1: AD036 single dose of drug combination (80mg/5mg) nightly for 30 days (oral capsule)
Group 2: AD036 single dose of drug combination (40mg/5mg) nightly for 30 days (oral capsule)
Group 3: AD036 single dose of drug combination (40mg/2.5mg) nightly for 30 days (oral capsule)
Group 4: Placebo pill nightly for 30 days (oral capsule)

First night of medication to be administered in-laboratory. Weekly telephone calls by the researcher to ensure participant adherence. Last night of treatment to be administered in-laboratory.
Intervention code [1] 315101 0
Treatment: Drugs
Comparator / control treatment
Group 4: Placebo (sugar pill) oral capsule nightly for 30 days
Control group
Placebo

Outcomes
Primary outcome [1] 320826 0
Change in apnoea/hypopnoea index (AHI) (high dose vs. placebo: primary efficacy outcome) measured via overnight sleep study
Timepoint [1] 320826 0
Day 30±4 post randomisation
Primary outcome [2] 320840 0
Potential adverse events across conditions will be assessed via clinical assessment during study visits including vital signs (e.g. potential changes in blood pressure assessed via arm cuff seated awake during study visits), participant self-reported potential side effects assessed during study visits and during weekly telephone calls using study-specific questionnaire and clinical laboratory testing.
Timepoint [2] 320840 0
Weekly from baseline during the 30 day trial plus day 45+2 post-commencement for end of study assessment.
Primary outcome [3] 320841 0
International Prostate Symptom Score (men only) across conditions
Timepoint [3] 320841 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [1] 372974 0
Epworth Sleepiness Scale (ESS) questionnaire (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [1] 372974 0
Bi-weekly from baseline during the 30 day trial plus day 45+2 post-commencement for end of study assessment.
Secondary outcome [2] 372987 0
Snoring index measuring via snoring senor during overnight sleep study (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [2] 372987 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [3] 373218 0
Patient Global Impression of OSA Severity (PGI-S) questionnaire (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [3] 373218 0
Bi-weekly from baseline during the 30 day trial plus day 45+2 post-commencement for end of study assessment.
Secondary outcome [4] 373219 0
Oxygen Desaturation Index 4% (ODI) measured via oximetry during the over night sleep study (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [4] 373219 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [5] 373220 0
Functional Outcomes of Sleep questionnaire (FOSQ) (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [5] 373220 0
Bi-weekly from baseline during the 30 day trial plus day 45+2 post-commencement for end of study assessment.
Secondary outcome [6] 373221 0
Total time with SaO2 <90% assessed via oximetry during overnight sleep study (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [6] 373221 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [7] 373222 0
Mean SaO2 assessed via oximetry during overnight sleep study (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [7] 373222 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [8] 373223 0
Minimum SaO2 assessed via oximetry during overnight sleep study (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [8] 373223 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [9] 373224 0
Proportion of participants with =50% Apnea Hypopnea Index (AHI) decrease assessed during overnight sleep study (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [9] 373224 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [10] 373225 0
Proportion of participants with more than 50% AHI decrease and final AHI less than 15/hour assessed during overnight sleep study (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [10] 373225 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [11] 373226 0
Arousal index assessed via EEG during overnight sleep study (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [11] 373226 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [12] 373227 0
At-home heart and respiratory rates assessed via the EarlySense device (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [12] 373227 0
Nightly during the 30 day study.
Secondary outcome [13] 373228 0
Psychomotor Vigilance Test (PVT) during the laboratory visit (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [13] 373228 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [14] 373229 0
AusEd driving simulator task during the laboratory visit (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [14] 373229 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [15] 373230 0
Karolinska Sleepiness Scale (KSS) questionnaire after awakening from sleep (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [15] 373230 0
Visit 1 and final visit during the 30 day trial.
Secondary outcome [16] 373231 0
Patient Global Satisfaction with Treatment questionnaire (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [16] 373231 0
End of study assessment day 45±2 from randomisation.
Secondary outcome [17] 373232 0
Insomnia severity index (ISI) questionnaire (high dose vs. placebo, other 2 arms vs. placebo and across the intervention arms)
Timepoint [17] 373232 0
Visit 1 and final visit during the 30 day trial.

Eligibility
Key inclusion criteria
Participants documented PSG within 1 year demonstrating AHI of 15 or higher.
Documented CPAP intolerance or poor compliance or CPAP naive.
Participants using CPAP at least 4 hours nightly are eligible for further screening and baseline PSG.
Previous surgical airway treatment for OSA allowed if more than 1 year prior to enrollment.
If male, International Prostate Symptom Score (IPSS) must be less than 15.
BMI between 18.5 and 40 kg/m^2.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.
8. History of drug abuse or substance use disorder as defined in DSM-V within 12 months prior to Screening Visit.
9. A significant acute illness or infection requiring medical treatment in the past 30 days.
10. Clinically significant cognitive dysfunction.
11. Untreated narrow angle glaucoma.
12. Women who are pregnant or nursing.
Prior/Concomitant Therapy
13. History of using oral or nasal devices for the treatment of OSA may enroll as long as the devices are not used during participation in the study.
14. History of using devices to affect participant sleeping position for the treatment of OSA, e.g. to discourage supine sleeping position, may enroll as long as the devices are not used during participation in the study.
15. History of oxygen therapy.
16. Use of medications from the list of disallowed concomitant medications.
17. 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 treatment, or concomitant with treatment.
Prior/Concurrent Clinical Study Experience
18. Use of another investigational agent within 30 days or 5 half-lives, whichever is longer, prior to dosing.
Diagnostic Assessments
19. ESS total score > 18.
20. Central apnea index > 5/hour on baseline PSG.
21. Periodic limb movement arousal index >15/hour on baseline PSG.

Other Exclusions
22. <5 hours typical sleep duration.
23. Night- or shift-work sleep schedule.
24. Employment as a commercial driver or operator of heavy or hazardous equipment.
25. Smoking more than 10 cigarettes or 2 cigars per day.
26. Unwilling to use specified contraception.
27. Unwilling to limit alcohol consumption to no greater than 2 units/day or less, not to be consumed within 3 hours of bedtime.
28. 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.
29. 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.
30. Participant considered by the investigator, for any reason, an unsuitable candidate to receive AD036 or unable or unlikely to understand or comply with the dosing schedule or study evaluations.

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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/08/2019
Actual
14/10/2019
Date of last participant enrolment
Anticipated
Actual
3/12/2020
Date of last data collection
Anticipated
Actual
17/12/2020
Sample size
Target
40
Accrual to date
Final
39
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 303198 0
Commercial sector/Industry
Name [1] 303198 0
Apnimed Australia Pty Ltd.
Country [1] 303198 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Sturt Rd, Bedford Park SA 5042
Country
Australia
Secondary sponsor category [1] 303420 0
None
Name [1] 303420 0
None
Address [1] 303420 0
None
Country [1] 303420 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303759 0
Southern Adelaide Clinical Research Ethics Committee
Ethics committee address [1] 303759 0
Ethics committee country [1] 303759 0
Australia
Date submitted for ethics approval [1] 303759 0
01/05/2019
Approval date [1] 303759 0
15/07/2019
Ethics approval number [1] 303759 0
101.19

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94698 0
Prof Danny Eckert
Address 94698 0
Adelaide Institute for Sleep Health, Flinders University,
Level 2, Mark Oliphant Building
5 Laffer Drive, Bedford Park SA 5042
Country 94698 0
Australia
Phone 94698 0
+61 8 74219780
Fax 94698 0
Email 94698 0
[email protected]
Contact person for public queries
Name 94699 0
Carolin Tran
Address 94699 0
Adelaide Institute for Sleep Health, Flinders University,
Level 2, Mark Oliphant Building
5 Laffer Drive, Bedford Park SA 5042
Country 94699 0
Australia
Phone 94699 0
+61 874219873
Fax 94699 0
Email 94699 0
[email protected]
Contact person for scientific queries
Name 94700 0
Danny Eckert
Address 94700 0
Adelaide Institute for Sleep Health, Flinders University,
Level 2, Mark Oliphant Building
5 Laffer Drive, Bedford Park SA 5042
Country 94700 0
Australia
Phone 94700 0
+61 874219780
Fax 94700 0
Email 94700 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
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseOne Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea A Randomized, Placebo-controlled Trial.2023https://dx.doi.org/10.1513/AnnalsATS.202207-594OC
EmbaseOne Month Dosing of Atomoxetine plus Oxybutynin in Obstructive Sleep Apnea: A Randomized, Placebo-controlled Trial.2023https://dx.doi.org/10.1513/AnnalsATS.202206-492OC
N.B. These documents automatically identified may not have been verified by the study sponsor.