- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04611750
Pharmacological Intervention for Symptomatic Mild Sleep Disordered Breathing
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a randomized placebo-controlled 2-period crossover study. Each crossover period will consist of 14 days of QHS dosing of either AD036 or placebo, with a washout period of 7 days between each period.
Polysomnography will be performed at screening (baseline) and on the last dosing day of each of the two crossover dosing period.
The trial will enroll participants until a total of 24 responders are randomized into the crossover portion of the study.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Victoria
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Clayton, Victoria, Australia, 3168
- Monash University
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Massachusetts
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Boston, Massachusetts, United States, 02141
- Brigham and Women's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
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 Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Active Medication (AD036)
Participants will take AD036 QHS for 14 days.
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AD036 will be given for 14 days
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PLACEBO_COMPARATOR: Placebo Medication
Participants will take placebo QHS for 14 days.
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Placebo will be given for 14 days
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Snoring Relationship Questionnaire (SRQ)
Time Frame: 14 days
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Self-reported impact of snoring on relationship and quality of life for patients and bedpartners, 0-20 scale, 0 lowest severity, 20 highest severity
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14 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Snoring Frequency
Time Frame: 14 days
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Snoring frequency, % breaths during sleep >100dB by tracheal microphone
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14 days
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Flow Limitation Frequency
Time Frame: 14 days
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Flow limitation frequency, % breaths during sleep >50% obstructed per airflow shape (Mann D et al ERJ)
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14 days
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Apnea-Hypopnea Index
Time Frame: 14 days
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Apnea-Hypopnea Index, events/hr (hypopneas per 4% desaturation)
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14 days
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Snoring Intensity
Time Frame: 14 days
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Mean tracheal sound pressure, presented in dB
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14 days
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Flow Limitation Severity, %
Time Frame: 14 days
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Median overnight flow limitation severity (Mann et al ERJ) in %, 0% is maximal flow limitation, 100% is absence of flow limitation
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14 days
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Hypoxic Burden
Time Frame: 14 days
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Area under curve of pulse oxygen saturation due to respiratory events (Azarbarzin et al EHJ method) in %desaturation.min/hr
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14 days
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Sleep Apnea Quality of Life Index (Short)
Time Frame: 14 days
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Sleep-related quality of life on 1-7 scale, 1 is lowest quality of life, 7 is highest quality of life
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14 days
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Snoring Self-Evaluation Survey (SSES)
Time Frame: 14 days
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Snoring-related symptoms and quality of life for the snorer on a 0-16 scale, 0 represents absence of snoring and related symptoms, 16 represents maximal snoring and related symptoms
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14 days
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Snoring Bedpartner-Evaluation Survey (SBES)
Time Frame: 14 days
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Snoring-related quality of life for the bedpartneron a 0-16 scale, 0 represents absence of snoring and related symptoms, 16 represents maximal snoring and related symptoms
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14 days
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Epworth Sleepiness Scale
Time Frame: 14 days
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Sleepiness 0-24 scale, 0 least sleepy, 24 most sleepy
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14 days
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Visual Analog Scale for Treatment Satisfaction
Time Frame: 14 days
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Treatment Satisfaction 0-10 scale, 0 most dissatisfied, 5 neutral, 10 most satisfied
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14 days
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Participant Global Impression of Severity (PGI-S) of SDB symptoms
Time Frame: 14 days
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Self-reported Symptom Severity 0-4 scale, 0 lowest severity, 4 highest severity
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14 days
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Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2020P002259
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Sleep Disordered Breathing
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Wayne State UniversityNational Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health...CompletedSleep-disordered BreathingUnited States
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University Hospital, AntwerpCompleted
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The Hospital for Sick ChildrenRecruitingSleep-Disordered BreathingCanada
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Brigham and Women's HospitalChildren's Hospital of Philadelphia; University of Michigan; Boston Children's... and other collaboratorsCompleted
-
Assiut UniversityUnknownObstructive Sleep Disordered BreathingEgypt
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The Cleveland ClinicWithdrawnObstructive Sleep Disordered BreathingUnited States
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Merz Pharmaceuticals GmbHWithdrawn
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Beijing Children's HospitalMerck Sharp & Dohme LLCUnknownSleep-disordered BreathingChina
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National Center for Research Resources (NCRR)CompletedSleep-Disordered BreathingUnited States
Clinical Trials on AD036
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ApnimedCompleted