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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04611750




Registration number
NCT04611750
Ethics application status
Date submitted
29/10/2020
Date registered
2/11/2020
Date last updated
2/03/2022

Titles & IDs
Public title
Pharmacological Intervention for Symptomatic Mild Sleep Disordered Breathing
Scientific title
Pharmacological Intervention for Symptomatic Mild Sleep Disordered Breathing
Secondary ID [1] 0 0
2020P002259
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sleep Disordered Breathing 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Respiratory 0 0 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AD036
Treatment: Drugs - Placebo

Experimental: Active Medication (AD036) - Participants will take AD036 QHS for 14 days.

Placebo Comparator: Placebo Medication - Participants will take placebo QHS for 14 days.


Treatment: Drugs: AD036
AD036 will be given for 14 days

Treatment: Drugs: Placebo
Placebo will be given for 14 days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Snoring Relationship Questionnaire (SRQ)
Timepoint [1] 0 0
14 days
Secondary outcome [1] 0 0
Snoring Frequency
Timepoint [1] 0 0
14 days
Secondary outcome [2] 0 0
Flow Limitation Frequency
Timepoint [2] 0 0
14 days
Secondary outcome [3] 0 0
Apnea-Hypopnea Index
Timepoint [3] 0 0
14 days

Eligibility
Key inclusion criteria
Inclusion Criteria at Enrollment:

- Between 25 to 70 years of age, inclusive

- SRQ at screening = 4 (at least mild impact of snoring)

- ESS at screening = 12 (absence of sleepiness)

- BMI between 18.5 and 40 kg/m2, inclusive.

- Use of specified contraceptive methods if appropriate

Inclusion Criteria for First Study Phase (Run-in Period):

- AHI =5-10, or AHI 0-<5 if either:

- Snoring frequency (100dB snoring for >10% of sleep) by tracheal microphone, or

- Flow limitation frequency (>50% obstruction for >10% of sleep).

- PGI-S that improves by at least 1 point during AD036 run-in period

Inclusion Criteria for Randomization:

• PGI-S that improves by at least 1 point during AD036 run-in period.
Minimum age
25 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants are excluded from the study if any of the following criteria apply:

- History of narcolepsy

- Clinically significant craniofacial malformation

- Clinically significant cardiac disease (e.g., rhythm disturbances, coronary artery
disease or cardiac failure) or hypertension requiring more than 2 medications for
control.

- Clinically significant neurological disorder, including epilepsy/convulsions.

- History of schizophrenia, schizoaffective disorder or bipolar disorder

- History of attempted suicide or suicidal ideation within 1 year prior to screening, or
current suicidal ideation.

- History of clinically significant constipation, gastric retention, or urinary
retention.

- Positive screen for drugs of abuse or substance use disorder

- A significant illness or infection requiring medical treatment in the past 30 days.

- Clinically significant cognitive dysfunction.

- Untreated narrow angle glaucoma.

- Women who are pregnant or nursing.

- History of using oral or nasal devices for the treatment of OSA or snoring; may enroll
as long as the devices are not used during participation in the study.

- History of using devices to affect participant sleeping position for the treatment of
OSA or snoring, e.g. to discourage supine sleeping position; may enroll as long as the
devices are not used during participation in the study.

- History of oxygen therapy (last 12 months).

- Use of medications from the list of disallowed concomitant medications during study
participation.

- MAOIs or other drugs that affect monoamine concentrations (e.g., rasagiline)
[MAOIs are contraindicated for use with atomoxetine]

- Selective Serotonin Reuptake Inhibitors (e.g., paroxetine)

- Selective Norepinephrine Reuptake Inhibitors (e.g., duloxetine)

- Norepinephrine Reuptake Inhibitors (e.g., reboxetine)

- Alpha-1 antagonists (e.g., tamsulosin)

- Tricyclic antidepressants (e.g., desipramine)

- Centrally acting antihypertensives (e.g. clonidine, alpha-methyl-DOPA)

- CYP2D6 inhibitors

- Strong CYP3A4 inhibitors (e.g., ketoconazole)

- Benzodiazepines and other anxiolytics or sedatives

- Nonbenzodiazepine hypnotics

- Opioids

- Muscle relaxants

- Pressor agents

- Drugs with clinically significant cardiac QT-interval prolonging effects

- Drugs known to lower seizure threshold (e.g., chloroquine)

- Amphetamines

- Antiepileptics

- Antiemetics

- Modafinil or armodafinil

- Beta2 agonists, (e.g., albuterol)

- Antipsychotics

- Anticholinergics and anticholinesterase inhibitors, including drugs with
substantial anticholinergic side effects, (e.g., first generation antihistamines)

- Sedating antihistamines

- Pseudoephedrine, phenylephrine, oxymetazoline

- Nicotine replacement products

- Most drugs for Parkinson's, Alzheimer's, Huntington's, Amyotrophic Lateral
Sclerosis, or drugs for other neurodegenerative diseases

- 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.

- Use of another investigational agent within 30 days or 5 half-lives prior to dosing,
whichever is longer.

- <5 hours typical sleep duration.

- Smoking more than 10 cigarettes or 2 cigars per day.

- Unwilling to use specified contraception.

- Unwilling to limit alcohol consumption to no greater than 2 units/day or less for men,
or 1 unit/day for women, not to be consumed within 3 hours of bedtime.

- Unwilling to limit caffeinated beverage intake (e.g., coffee, cola, tea) to 400 mg/day
or less of caffeine (approximately 4 cups of coffee); caffeine not to be used within 3
hours of bedtime.

- 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.

- 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
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/01/2022
Sample size
Target
Accrual to date
Final
53
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash University - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts

Funding & Sponsors
Primary sponsor type
Other
Name
Brigham and Women's Hospital
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Apnimed
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Currently, there is no pharmacological intervention for mild symptomatic obstructive sleep
disordered breathing (SDB) in the form of loud habitual snoring, inspiratory flow limitation
(i.e. upper airway resistance syndrome), or mild sleep apnea. Here the investigators study
the effect on SDB of stimulating pharyngeal muscles during sleep with AD036. The key
hypothesis of the study is that AD036 is superior to placebo on self-reported and objective
measures of SDB severity.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04611750
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Scott A Sands, PhD
Address 0 0
Brigham and Women's Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries